Journal of Functional Biomaterials

26 pages, 4906 KB

Open AccessEditor’s ChoiceArticle

A Borophosphate Glass Doped with Cobalt Oxide Improves Skeletal Muscle Structure and Function in Myopathic Mice

by Jacob A. Kendra, Alexandra G. Naman, Rebekah L. Blatt, Carla D. Zingariello, Richard K. Brow, Steven S. Segal and Aaron B. Morton

J. Funct. Biomater. 2026, 17(3), 155; https://doi.org/10.3390/jfb17030155 - 20 Mar 2026

Viewed by 1417

Abstract

Skeletal muscle myopathy remains a significant cause of disability with limited treatment strategies. Advancements in tissue engineering have led to the development of borophosphate bioactive glasses (BPBGs) capable of enhancing skeletal muscle structure and function. Using a mouse model of severe myopathy (D2. [...] Read more.

Skeletal muscle myopathy remains a significant cause of disability with limited treatment strategies. Advancements in tissue engineering have led to the development of borophosphate bioactive glasses (BPBGs) capable of enhancing skeletal muscle structure and function. Using a mouse model of severe myopathy (D2.mdx), we investigated muscle force, regeneration, angiogenesis and inflammation at 14, 70 and 140 days post-treatment (dpt). Tibialis anterior (TA) muscles of D2.mdx mice that received a single injection of cobalt oxide-doped BPBG (CoO-TRIM) particles exhibit greater active force, myofiber size, and regeneration through 70 dpt compared to control D2.mdx mice injected with Saline. Vascular endothelial growth factor (VEGF) was elevated up to 70 dpt in D2.mdx CoO-TRIM mice followed by increased muscle vascularity. As a marker of inflammation, interleukin (IL)-6 increased in D2.mdx CoO-TRIM mice compared to D2.mdx Saline controls at 14 dpt, with no differences at 70 or 140 dpt. No differences were observed in outcome measures between wild-type (WT) CoO-TRIM mice and WT Saline controls. We report that CoO-TRIM can stimulate VEGF production and promote restoration of muscle structure and function when inflammation is present. Local injection of an inorganic biomaterial alone can benefit myopathic skeletal muscle. Full article

(This article belongs to the Special Issue Application of Biomaterials in Tissue Engineering and Regenerative Medicine—2nd Edition)

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27 pages, 7352 KB

Open AccessEditor’s ChoiceArticle

Cytocompatibility Assessment of L-PBF-Manufactured Zinc–Silver–Copper Alloys for Customized Biodegradable Medical Implants

by Barbara Illing, Jacob Schultheiss, Lukas Schumacher, Evi Kimmerle-Mueller, Ariadne Roehler, Alexander Heiss, Ulrich E. Klotz, Victor O. Okafor, Stefanie Krajewski and Frank Rupp

J. Funct. Biomater. 2026, 17(3), 146; https://doi.org/10.3390/jfb17030146 - 17 Mar 2026

Viewed by 1637

Abstract

Biodegradable zinc (Zn) has attracted increasing interest as a material for temporary implants, primarily due to its moderate degradation kinetics. In recent years, additive manufacturing of Zn alloys using the laser powder bed fusion method (L-PBF) has shown promising results. Compared to as-cast [...] Read more.

Biodegradable zinc (Zn) has attracted increasing interest as a material for temporary implants, primarily due to its moderate degradation kinetics. In recent years, additive manufacturing of Zn alloys using the laser powder bed fusion method (L-PBF) has shown promising results. Compared to as-cast Zn alloys, it offers preferable customized solutions for patient-specific temporary biomedical implants. Due to the novelty of these printed degradable biomaterials and due to reported cytotoxic effects of Zn alloys, this study investigates additively manufactured ZnAgCu, ZnAgCuMn, and ZnAgCuTi alloys, both in as-printed and post-processed conditions, with a focus on L929 and SAOS-2 biocompatibility. In this work, we demonstrate that the increased porosity and therefore larger surface areas compared to polished Zn-alloy samples affect their biocompatibility. Minimal to no cell proliferation was observed on and near the Zn-alloy test plates after 24 h. Undiluted extracts from as-cast Zn and L-PBF-manufactured plates were initially cytotoxic to SAOS-2 cells. However, as passivation proceeded, cytocompatibility was significantly increased from day 3 onward. Zn²⁺ ion release peaked at 24 h and declined significantly from day 2 to day 10. Compared to the other Zn alloys, ZnAgCuMn exhibited the lowest cytocompatibility. Most intriguingly, 3-month surfaces exhibited reduced cytocompatibility to osteoblasts compared to freshly polished samples. The observed in vitro cytotoxicity motivates further investigation of as-printed and post-processed L-PBF-manufactured Zn alloys, aiming to develop novel surface modification strategies to mitigate the initial ion burst responsible for reduced cytocompatibility and to adjust and tailor the overall degradation kinetics to physiologically tolerable levels tailored to the intended clinical application. Full article

(This article belongs to the Special Issue Biocompatible Research of Materials in Biomedical Applications)

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12 pages, 1137 KB

Open AccessEditor’s ChoiceArticle

Development of Freeze-Dried Hyaluronic Acid Sheets for Healing Oral Mucositis: Influence of Hyaluronic Acid Molecular Weight and Nicotinamide Mononucleotide Loading on Healing Efficacy

by Akiko Tanaka, Takanobu Takata, Hidemasa Katsumi, Yasuhisa Sawai, Hiroyuki Nakano, Chika Yoneto, Kunio Yoneto, Tomoyuki Furubayashi and Toshiyasu Sakane

J. Funct. Biomater. 2026, 17(3), 137; https://doi.org/10.3390/jfb17030137 - 10 Mar 2026

Viewed by 1177

Abstract

Oral mucositis frequently develops during radiotherapy or chemotherapy for head and neck cancer and is characterized by severe pain and impaired eating and speech. It was previously demonstrated that freeze-dried hyaluronic acid (HA) sheets effectively promote the healing of oral mucosal ulcers. This [...] Read more.

Oral mucositis frequently develops during radiotherapy or chemotherapy for head and neck cancer and is characterized by severe pain and impaired eating and speech. It was previously demonstrated that freeze-dried hyaluronic acid (HA) sheets effectively promote the healing of oral mucosal ulcers. This study aimed to optimize the HA sheet formulation by evaluating the effects of HA molecular weight and nicotinamide mononucleotide (NMN) loading on therapeutic efficacy. HA sheets were prepared using HA with four different molecular weights (50, 350, 800, and 2000 kDa), and their therapeutic effects were evaluated in an animal oral ulcer model using 6-week-old male Syrian hamsters. Among the formulations tested, the 800 kDa HA sheet exhibited the greatest healing efficacy, and it showed an excellent balance between buccal retention and the sustained release of NMN for the treatment of oral mucositis. In vitro cytotoxicity assays confirmed that HA, with or without NMN, was non-toxic and suitable for local applications. These findings indicate that HA sheets, particularly those composed of 800 kDa HA, may represent a promising and biocompatible mucoadhesive material for the delivery of NMN and the local treatment of oral mucositis associated with head and neck cancer. Full article

(This article belongs to the Special Issue 15th Anniversary of JFB—Advanced Biomaterials for Drug Delivery)

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13 pages, 2757 KB

Open AccessEditor’s ChoiceArticle

Silk Fibroin Sheets Improve the Strength of Colon Anastomoses in Wistar Rats

by Mohamed Hassin Mohamed Chairi, Francisco José Huertas Peña, Jorge García-García, Laura López-Escánez, Salvador D. Aznar-Cervantes, Patricia Becerra Massare, Julio Gálvez, Per Anderson, José Alberto Molina-Tijeras and María Elena Rodríguez-Cabezas

J. Funct. Biomater. 2026, 17(3), 126; https://doi.org/10.3390/jfb17030126 - 4 Mar 2026

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Abstract

Colorectal resection and subsequent anastomosis are the standard curative procedures for a variety of colorectal pathologies. However, anastomotic leakage (AL) is an early and frequent complication that can have life-threatening outcomes. The study aimed to evaluate the effect of silkworm fibroin sheets on [...] Read more.

Colorectal resection and subsequent anastomosis are the standard curative procedures for a variety of colorectal pathologies. However, anastomotic leakage (AL) is an early and frequent complication that can have life-threatening outcomes. The study aimed to evaluate the effect of silkworm fibroin sheets on colon anastomotic strength and wound healing early after intervention in Wistar rats. Male Wistar rats were randomized into two groups, control (N = 11) and fibroin (N = 11), and subjected to end-to-end colo-colic anastomosis. In the fibroin group, a single layer of fibroin membrane was applied externally around the anastomosis. The animals were sacrificed three days after the operation (POD3) and intestinal adhesions, anastomotic bursting pressure and histological parameters based on the eosin, hematoxylin, and Masson’s trichrome stains were compared between the groups. Fibroin-treated rats showed a significant increase in anastomotic bursting pressure compared to control animals (69 (18) vs. 41 (28) mmHg), whereas no differences in the intestinal adhesion scores were detected. No significant differences in the numbers of granulocytes, monocytes/macrophages and fibroblasts, nor the amount of collagen fibers, as measured by Masson’s trichrome stain, were found between the groups. These results indicate that fibroin sheets could represent a simple and promising tool to provide mechanical support and improve colonic anastomotic strength early after intervention. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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25 pages, 9804 KB

Open AccessEditor’s ChoiceArticle

LXW7 Peptide Modification of Acellular Liver Scaffolds Improves Endothelialization and Hemocompatibility in Bioengineered Liver

by Usha Yadav, Chandra J. Yadav, Sadia Afrin, Jun-Yeong Lee, Jihad Kamel and Kyung-Mee Park

J. Funct. Biomater. 2026, 17(3), 122; https://doi.org/10.3390/jfb17030122 - 3 Mar 2026

Viewed by 1208

Abstract

End-stage liver disease caused by advanced fibrosis and cirrhosis remains a major global burden, yet its treatment is limited by donor organ shortages. Bioengineered liver scaffolds offer a promising alternative, but their efficacy is often limited by thrombosis, insufficient vascularization, and poor graft [...] Read more.

End-stage liver disease caused by advanced fibrosis and cirrhosis remains a major global burden, yet its treatment is limited by donor organ shortages. Bioengineered liver scaffolds offer a promising alternative, but their efficacy is often limited by thrombosis, insufficient vascularization, and poor graft integration due to inadequate endothelialization. To overcome these challenges, we employed LXW7 αvβ3 integrin targeting peptide with high endothelial cell specificity and low platelet affinity to enhance re-endothelialization and hemocompatibility of decellularized liver scaffold (DLS) and thereby improve hepatic integration and function. LXW7 was covalently conjugated to the decellularized rat liver scaffold via EDC/NHS-mediated carbodiimide coupling and subsequently reseeded with human umbilical vein endothelial cells (HUVECs) and cultured in a perfusion bioreactor to promote endothelialization. LXW7 immobilization significantly improved HUVECs attachment and proliferation, achieving approximately 81% vascular coverage, while sustaining the endothelial function. Ex vivo blood perfusion showed minimal thrombus formation and markedly reduced platelet adhesion, demonstrating enhanced hemocompatibility. Following confirmation of endothelialization, scaffolds were recellularized with hepatocellular carcinoma (HepG2) cells and HUVECs. LXW7 modified scaffolds promote organized hepatocyte distribution, sustained albumin expression, and increased urea secretion. In vivo implantation of LXW7-DLS into the omentum of mice promoted robust host endothelial recruitment and enhanced neovascularization, highlighting the scaffold’s excellent biocompatibility and good integration with surrounding tissues. Moreover, in vivo implantation of LXW7 recellularized scaffolds into a thioacetamide-induced fibrotic mouse liver resulted in reduced collagen deposition and lowered serum ALT/AST levels, demonstrating hepatic regeneration and extracellular matrix remodeling. Overall, our results showed that LXW7-modified DLS promotes stable endothelialization, improves hemocompatibility, and enhances hepatic function, underscoring its translational potential for the development of vascularized transplantable liver grafts. Full article

(This article belongs to the Special Issue Surface Coating, Functionalization, and Characterization of Cell- and Tissue-Based Biomaterials)

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18 pages, 3889 KB

Open AccessEditor’s ChoiceArticle

A Pre-Set Calcium Sulfate/Hydroxyapatite Biomaterial as an Antibiotic-Eluting Bone Extender and a Carrier for BMP-2: A Pilot Study in a Rabbit Posterolateral Spinal Fusion Model

by Jintian Huang, Gintarė Lukoševičiūtė, Filip Mrkonjic, Hadis Alidadi, Domantas Jakstas, Sujeesh Sebastian, Lars Lidgren, Magnus Tägil and Deepak Bushan Raina

J. Funct. Biomater. 2026, 17(3), 118; https://doi.org/10.3390/jfb17030118 - 1 Mar 2026

Viewed by 1168

Abstract

Synthetic biomaterials used as bone graft extenders (BGE) in spinal fusion surgery can supplement but do not replace autologous bone. This pilot study evaluated a calcium sulfate/hydroxyapatite (CaS/HA) material as an antibiotic-eluting BGE and a carrier for bone morphogenetic protein-2 (BMP-2) in a [...] Read more.

Synthetic biomaterials used as bone graft extenders (BGE) in spinal fusion surgery can supplement but do not replace autologous bone. This pilot study evaluated a calcium sulfate/hydroxyapatite (CaS/HA) material as an antibiotic-eluting BGE and a carrier for bone morphogenetic protein-2 (BMP-2) in a rabbit posterolateral lumbar (L4–L5) spinal fusion model (PLF). Pre-set CaS/HA beads were loaded with tobramycin (TOB) and tested for in vitro antibiotic release and antibacterial activity against Staphylococcus aureus. For the in vivo PLF study, CaS/HA beads were used in two treatment strategies: (1) CaS/HA + TOB + autograft (left side) and (2) CaS/HA + BMP-2 (right side). Serum levels of TOB were quantified and spinal fusion was evaluated after 12 weeks. TOB exhibited a rapid initial release, followed by a decline below detectable levels after 6 h in vitro and 48 h in vivo. TOB-loaded CaS/HA beads demonstrated in vitro antibacterial activity for 19 days. In the PLF study, 5/6 and 6/6 specimens were fused radiologically in the TOB and BMP groups, respectively, and 100% using mechanical testing. Micro-CT analysis showed no significant difference in bone volume between the TOB and BMP-2 groups (364 ± 84 vs. 479 ± 95 mm³). Histology verified continuous bone bridging in both groups. Our in vitro findings indicate that locally added TOB could protect the CaS/HA material from bacterial colonization and did not adversely impact the CaS/HA material negatively to act as BGE. The addition of low-dose BMP-2 to the CaS/HA material proved effective in building bone without the need to harvest autologous bone. In summary, this pilot PLF study demonstrates that the tested CaS/HA material combined with BMP-2 could replace autologous bone harvesting in spinal fusion surgery. Addition of TOB could potentially protect the material from bacterial colonization during the early post-operative period but further studies in infection models are warranted. Full article

(This article belongs to the Section Biomaterials for Drug Delivery)

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16 pages, 2393 KB

Open AccessEditor’s ChoiceArticle

Parameter Optimisation in 3D Extrusion Printing of Polyhydroxybutyrate Using Design of Experiment Methodology

by Mingzu Du, Giuseppe Tronci, Xuebin B. Yang and David J. Wood

J. Funct. Biomater. 2026, 17(2), 90; https://doi.org/10.3390/jfb17020090 - 12 Feb 2026

Viewed by 1113

Abstract

This study systematically optimised extrusion-printing parameters for polyhydroxybutyrate (PHB) using a Design of Experiment (DoE) approach to improve printability and construct fidelity. A five-factor DoE was conducted to evaluate the individual and interactive effects of printhead temperature, printing pressure, printing speed, bed temperature, [...] Read more.

This study systematically optimised extrusion-printing parameters for polyhydroxybutyrate (PHB) using a Design of Experiment (DoE) approach to improve printability and construct fidelity. A five-factor DoE was conducted to evaluate the individual and interactive effects of printhead temperature, printing pressure, printing speed, bed temperature, and cartridge heating time on the dimensional accuracy of printed constructs. The resulting regression model enabled the identification of statistically significant main and interaction effects among processing variables. An optimised parameter set (printhead temperature 145 °C, pressure 150 kPa, speed 15 mm s⁻¹, bed temperature 25 °C, and cartridge heating time 120 s) enabled the fabrication of PHB scaffolds with substantially improved shape fidelity, which was experimentally validated using verification prints. These results demonstrate that a DoE-based optimisation strategy provides a robust and efficient route for rationally tuning PHB extrusion-printing conditions, thereby enhancing process reliability for scaffold fabrication in regenerative medicine applications. Full article

(This article belongs to the Special Issue 3D Printing Biomaterials and Technologies in Biomedical Applications)

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13 pages, 1583 KB

Open AccessEditor’s ChoiceArticle

Comparative Finite Element Evaluation of Polymeric and Metallic Bioresorbable Sinus Stents Under Quasi-Static Radial Compression

by Wenyu Fu, Aiping Yang and Aike Qiao

J. Funct. Biomater. 2026, 17(2), 83; https://doi.org/10.3390/jfb17020083 - 8 Feb 2026

Viewed by 1526

Abstract

To address the issues of displacement and insufficient positional stability observed in the clinical use of the PROPEL Mini stent, this study investigates the influence of different biodegradable materials on the mechanical properties of the stent under the constraint of a fixed monofilament [...] Read more.

To address the issues of displacement and insufficient positional stability observed in the clinical use of the PROPEL Mini stent, this study investigates the influence of different biodegradable materials on the mechanical properties of the stent under the constraint of a fixed monofilament braided closed-loop geometry. Finite element analyses are conducted using Abaqus/Explicit to quantitatively evaluate the nonlinear mapping between nominal diameter, axial length, and radial pressure throughout a loading–unloading cycle. The results reveal that while axial behavior is consistent during compression, material-specific plasticity causes irreversible geometric sets in Mg alloy and PLGA models, whereas the PCL stent achieves total elastic recovery to its initial dimensions. During unloading, the Mg alloy stent recovers to a nominal diameter of 28 mm with a reduced axial length of approximately 22 mm, whereas the PLGA stent exhibits a much smaller recovery diameter of 14 mm with an axial length of approximately 23 mm. These post-release configurations directly determine the functional expansion range of the biodegradable stents after implantation. During unloading, the Mg alloy stent provides the highest radial pressure (peak 6.8 kPa) with a functional recovery range up to 26.5 mm, ensuring superior scaffolding stability. In contrast, while PCL achieves the widest recovery (52 mm), its radial pressure is clinically negligible (the maximum value is still less than 165 Pa), and the PLGA model exhibits both insufficient support and a restricted functional recovery limit (13 mm). By using high-strength materials such as Mg alloys, the radial anchoring force of the stent can be effectively enhanced without changing the existing structure, providing a scientific basis for solving clinical displacement problems. Full article

(This article belongs to the Special Issue Metals and Alloys for Biomedical Applications (2nd Edition))

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18 pages, 1640 KB

Open AccessEditor’s ChoiceReview

Functionalized Biomaterials in the Investigation of the Effects of Fluid Shear Forces in the Immune Regulation of Cancer Progression and Metastasis

by Rayhaneh Afjei and Vassilios I. Sikavitsas

J. Funct. Biomater. 2026, 17(2), 81; https://doi.org/10.3390/jfb17020081 - 7 Feb 2026

Viewed by 1056

Abstract

As cancer mortality rates rise globally, malignancies have become the second leading cause of death. Recently, efforts have been made to understand the impact of the tumor microenvironment that involves fluid shear forces. Biomechanical stimulation, which uses shear stress to activate mechanosensitive ion [...] Read more.

As cancer mortality rates rise globally, malignancies have become the second leading cause of death. Recently, efforts have been made to understand the impact of the tumor microenvironment that involves fluid shear forces. Biomechanical stimulation, which uses shear stress to activate mechanosensitive ion channels, e.g., Piezo1, increases calcium influx into the intracellular space and activates T cells. Novel 3D cancer cultures with T cells have been proposed. Such models use cell/scaffold constructs to recapitulate interactions between cells and the extracellular matrix. In addition, flow perfusion bioreactors investigate the impact of fluid shear forces on immune and/or cancer cells. These bioreactors have biosensors that allow monitoring of immune cell activation. Furthermore, they provide a biomimetic environment for the study of the interaction of T cells and cancer cells. Hence, immune checkpoint inhibitors have demonstrated immunotherapeutic efficacy, but a single-target blockade has often proved insufficient. Co-delivery of CCL19 pDNA and the PD-1/PD-L1 interaction inhibitor BMS-1 using RGD-modified nanocarriers targeting tumor integrins enhanced local antitumor immunity. This review highlights recent insights into how fluid shear stress (FSS) regulates cancer progression and immune responses in three-dimensional in vitro models, with a focus on bioreactors and the surface modification of scaffold materials. Full article

(This article belongs to the Special Issue Design, Synthesis, Detection, Diagnosis and Therapeutic Applications of Bioactive Materials)

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20 pages, 741 KB

Open AccessEditor’s ChoiceSystematic Review

Histological Tissue Response to Calcium Silicate-Based Cements Assessed in Human Tooth Culture Models: A Systematic Review

by Alberto Cabrera-Fernández, Hebertt Gonzaga dos Santos Chaves, Aránzazu Díaz-Cuenca, Juan J. Segura-Egea, Jenifer Martín-González, João Peça, Diana B. Sequeira and João Miguel Marques dos Santos

J. Funct. Biomater. 2026, 17(2), 78; https://doi.org/10.3390/jfb17020078 - 6 Feb 2026

Cited by 1 | Viewed by 1727

Abstract

Ex vivo human tooth culture models preserve the native dentine–pulp complex and offer a translational platform to study pulp-capping biomaterials. This systematic review aimed to synthesize the evidence on histological pulp tissue responses to calcium silicate-based cement (CSCs) used for direct pulp capping [...] Read more.

Ex vivo human tooth culture models preserve the native dentine–pulp complex and offer a translational platform to study pulp-capping biomaterials. This systematic review aimed to synthesize the evidence on histological pulp tissue responses to calcium silicate-based cement (CSCs) used for direct pulp capping in human tooth culture models. The review followed PRISMA 2020 guidance. Eligible studies were ex vivo whole human tooth culture models with direct pulp exposure treated with commercial or experimental CSCs and reporting histological outcomes. Risk of bias was assessed using the QUIN tool. Thirteen studies were included. Most used immature human third molars (from 15- to 19-year-old patients) and culture periods up to 28 days, with a minority extending observation to 45–90 days. Across hydraulic CSCs, Biodentine was the most frequently evaluated material, followed by ProRoot MTA and several experimental hydraulic and resin-modified formulations. Overall, hydraulic CSCs were consistently associated with biocompatible pulp responses and a pro-mineralization pattern characterized by periexposure mineralized foci/osteodentin-like tissue; where assessed, immunohistochemistry supported odontoblast-like differentiation. In contrast, the resin-modified CSC TheraCal LC and other experimental resin-modified CSCs showed more heterogeneous findings, with reports of absent, delayed, or less prominent mineralization compared with reference hydraulic CSCs. In intact human tooth culture models, hydraulic CSCs show reproducible biocompatibility and early mineralization features consistent with reparative dentinogenesis, whereas resin-modified CSCs demonstrate more variable histological performance. Full article

(This article belongs to the Special Issue The 15th Anniversary of JFB—Endodontic Biomaterials)

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25 pages, 9924 KB

Open AccessEditor’s ChoiceArticle

Superhydrophilic Hierarchical Anatase Coating on Sandblasted, Acid-Etched Titanium: In Vitro Apatite Formation and Osteoblast Responses and the Role of Polar Surface Free Energy

by Leila Mohammadnejad, Wafa Zafira, Jacob Schultheiss, Lenny Crocoll, Evi Kimmerle-Mueller, Barbara Illing, Katharina Keppeler, Markus Turad, Annika Hechler, Christiane von Ohle, Julia Stahl, Frank Rupp and Stefanie Krajewski

J. Funct. Biomater. 2026, 17(2), 80; https://doi.org/10.3390/jfb17020080 - 6 Feb 2026

Cited by 2 | Viewed by 1035

Abstract

Physicochemical modification of titanium implants aims to enhance early osseointegration by improving bioactivity. This study deposited and evaluated an anatase TiO₂ film on clinically relevant sandblasted, acid-etched titanium (Ti-SLA) to enhance in vitro bioactivity and osteogenic responses. An ~8 µm TiO₂ [...] Read more.

Physicochemical modification of titanium implants aims to enhance early osseointegration by improving bioactivity. This study deposited and evaluated an anatase TiO₂ film on clinically relevant sandblasted, acid-etched titanium (Ti-SLA) to enhance in vitro bioactivity and osteogenic responses. An ~8 µm TiO₂-anatase coating was deposited on Ti-SLA by reactive pulsed DC magnetron sputtering. Surface characterization included FE-SEM, helium ion microscopy, and XRD. Wettability and surface free energy (SFE) were evaluated by contact angle analysis. In vitro bioactivity was assessed by hydroxyapatite (HA) formation in twofold-concentrated simulated body fluid (2× SBF). Osteoblast responses were evaluated through cell adhesion, viability, alkaline phosphatase activity, gene expression, and mineralization. The coating produced hierarchical multi-globular microstructures decorated with faceted anatase nanocrystals. Ti-SLA’s initial hydrophobicity converted to a superhydrophilic, high-energy surface with increased polar SFE. Homogeneous HA crystallites deposited exclusively on SLA-anatase in 2× SBF. SAOS-2 cells showed enhanced metabolic activity, ALP activity, osteogenic gene upregulation, and improved mineralized matrix, while primary human osteoblasts exhibited increased metabolic activity and calcium deposition. The anatase coating produced a superhydrophilic, high-energy micro-nano surface that accelerates HA formation and enhances osteoblast function in vitro, warranting in vivo validation for early osseointegration. Full article

(This article belongs to the Special Issue Spotlight on Biomedical Coating Materials)

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17 pages, 3186 KB

Open AccessEditor’s ChoiceArticle

Tooth Root-Derived Graft Promotes Complete Bone Replacement in Alveolar Ridge Preservation: Comparative Study with a Collagenic Xenograft in Dogs

by Yasushi Nakajima, Takahisa Iida, Elio Minetti, Maria Permuy, Giuliano Roberto, Ermenegildo Federico De Rossi, Giovanna Iezzi and Daniele Botticelli

J. Funct. Biomater. 2026, 17(2), 77; https://doi.org/10.3390/jfb17020077 - 5 Feb 2026

Cited by 3 | Viewed by 859

Abstract

Background: Autogenous tooth-derived grafts have been proposed as an alternative to xenografts for alveolar ridge preservation, offering biological similarity to bone and potentially more favorable remodeling. This study compared the healing outcomes of a collagenated xenograft, and a tooth-derived graft prepared with an [...] Read more.

Background: Autogenous tooth-derived grafts have been proposed as an alternative to xenografts for alveolar ridge preservation, offering biological similarity to bone and potentially more favorable remodeling. This study compared the healing outcomes of a collagenated xenograft, and a tooth-derived graft prepared with an automated processing device. Methods: Six Beagle dogs underwent bilateral extraction of the third and fourth mandibular premolars. Each animal contributed two sockets grafted with root-derived particulate prepared using an automated device for tooth cleaning, grinding, and demineralization, and two sockets grafted with a collagenated xenograft, all covered by a collagen membrane. After 3 months, histological sections were analyzed to assess crestal dimensions and the relative proportions of mature (lamellar) and immature bone (woven/parallel fibered), residual graft material, and soft tissues. Results: Lingual crest height did not differ between groups, whereas the buccal crest was slightly higher at xenograft sites compared with the tooth-graft sites. The tooth-graft group exhibited significantly fewer residual particles (0.5 ± 1.1%) and a higher proportion of total bone (65.6 ± 9.1%) compared with the xenograft group, which showed 19.7 ± 16.0% graft remnants (p = 0.032). Corticalization at the socket entrance was observed predominantly in the tooth-graft sites. No inflammatory infiltrates were detected in the examined section. Conclusions: Tooth-derived grafts promoted an almost complete replacement by vital bone with minimal residual material, whereas xenografts provided slightly better buccal contour preservation but resulted in regenerated tissues containing persistent graft particles. The biological differences observed may have implications for subsequent implant placement. Full article

(This article belongs to the Section Bone Biomaterials)

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23 pages, 4189 KB

Open AccessEditor’s ChoiceArticle

Comparative Effects of Cellulose- and Gelatin-Based Hemostatic Biomaterials on the Early Stage of Wound Healing—An In Vivo Study

by Helena Hae In Ströthoff, Polina Shabes, Katharina Henrika Beckamp, Markus Udo Wagenhäuser, Wiebke Ibing, Julian-Dario Rembe, Hubert Schelzig and Waseem Garabet

J. Funct. Biomater. 2026, 17(2), 64; https://doi.org/10.3390/jfb17020064 - 27 Jan 2026

Cited by 1 | Viewed by 1289

Abstract

Hemostatic biomaterials are widely used in surgical and trauma settings, yet their influence on early wound healing remains incompletely understood. This in vivo study investigated the effects of cellulose- and gelatin-based hemostatic biomaterials on early wound healing using a murine skin wound model. [...] Read more.

Hemostatic biomaterials are widely used in surgical and trauma settings, yet their influence on early wound healing remains incompletely understood. This in vivo study investigated the effects of cellulose- and gelatin-based hemostatic biomaterials on early wound healing using a murine skin wound model. Oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a porcine gelatin-based matrix (GELA) were left in situ following standardized subcutaneous implantation and compared with sham-treated controls. Tissue responses were analyzed at postoperative days 3 and 7 using histology, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR). Cellulose-based materials persisted as eosinophilic remnants, whereas fibrous matrix structures and enhanced extracellular matrix deposition were observed in the GELA group. Immunohistochemical analysis revealed increased cluster of differentiation 68 (CD68)–positive macrophage presence in the ORC group at day 3 and in the GELA group at day 7, indicating biomaterial-dependent modulation of macrophage involvement during early wound healing. Expression of Kiel 67 (Ki-67), a marker of cellular proliferation, was significantly elevated in the epidermis of the GELA group at day 7, suggesting enhanced proliferative activity during the reparative phase. In contrast, no significant differences were detected in the expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), or cluster of differentiation 14 (CD14) between groups. Overall, none of the investigated biomaterials impaired early wound healing, while the gelatin-based material demonstrated features consistent with enhanced reparative cellular responses without excessive inflammation. Full article

(This article belongs to the Special Issue Biomaterials for Hemostasis and Wound Healing Applications)

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22 pages, 3970 KB

Open AccessEditor’s ChoiceArticle

Electrospun Phage-Loaded Bilayer Nanofibrous Scaffolds for Wound Dressing Applications: A Comparative Study of Different Bacteriophages

by Siavash Aghili, Muhammed Awad, Md Hasib Adnan, George Bouras, Tran Thanh Tung, Sarah Vreugde and Dusan Losic

J. Funct. Biomater. 2026, 17(2), 60; https://doi.org/10.3390/jfb17020060 - 26 Jan 2026

Cited by 1 | Viewed by 1387

Abstract

Antimicrobial resistance is a growing global health threat, necessitating alternatives to conventional antibiotics. Bacteriophages, viruses that specifically target bacteria, represent a promising option, and phage-loaded electrospun fibers have recently gained attention as wound dressings for localized phage therapy. However, the influence of phage [...] Read more.

Antimicrobial resistance is a growing global health threat, necessitating alternatives to conventional antibiotics. Bacteriophages, viruses that specifically target bacteria, represent a promising option, and phage-loaded electrospun fibers have recently gained attention as wound dressings for localized phage therapy. However, the influence of phage morphology and scaffold design has been largely overlooked. This study investigates how phage morphology and structure, in conjunction with scaffold design and processing conditions, may influence the biological performance of electrospun scaffolds. A bilayer scaffold was developed comprising a supportive polycaprolactone (PCL)/gelatin (70:30) layer and a polyvinyl alcohol (PVA) top layer loaded with bacteriophages. Two phage types, short-tailed podovirus APTC-SL.1 and long-tailed myovirus APTC-Efa.20, were incorporated into PVA fibers to evaluate their antibacterial activity against Staphylococcus lugdunensis and Enterococcus faecalis, respectively. The fibers were characterized using XRD, FTIR, TGA, optical microscopy, SEM, TEM, wettability analysis, and in vitro degradation tests. Biological assessments included antimicrobial testing, phage viability, and phage release. The bilayer scaffold containing short-tailed phages preserved phage viability and produced clear zones of lysis against S. lugdunensis, with ≈8.15% viability retained after electrospinning and relatively controlled release, whereas long-tailed phages showed no antibacterial activity. These results suggest that phage structure and morphology, together with electrospinning conditions and scaffold architecture, may play an important role in maintaining phage functionality in wound dressing applications, while acknowledging that host–phage interactions may also contribute to the observed differences. Full article

(This article belongs to the Section Antibacterial Biomaterials)

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19 pages, 2602 KB

Open AccessEditor’s ChoiceArticle

Laser-Enhanced Biomorphic Scaffolds Support Multipotent Stem Cell Differentiation and Angiogenesis for Vascularised Bone Regeneration

by Sandeep Kumar, Neelam Iqbal, Yahui Pan, Evangelos Daskalakis, Heather Elizabeth Owston, El Mostafa Raif, Payal Ganguly, Sarathkumar Loganathan, Peter V. Giannoudis and Animesh Jha

J. Funct. Biomater. 2026, 17(2), 62; https://doi.org/10.3390/jfb17020062 - 26 Jan 2026

Viewed by 1075

Abstract

Biomorphic hydroxyapatite scaffolds derived from rattan wood (GreenBone) show significant promise in bone tissue engineering due to their inherent structural similarity to natural bone. Laser-drilled GreenBone scaffolds were studied for enhanced porosity, nutrient diffusion, cellular infiltration, and vascularisation. Patient-derived bone marrow mesenchymal stromal/stem [...] Read more.

Biomorphic hydroxyapatite scaffolds derived from rattan wood (GreenBone) show significant promise in bone tissue engineering due to their inherent structural similarity to natural bone. Laser-drilled GreenBone scaffolds were studied for enhanced porosity, nutrient diffusion, cellular infiltration, and vascularisation. Patient-derived bone marrow mesenchymal stromal/stem cells (BMMSCs) and culture-expanded mesenchymal stem cells (cMSCs) demonstrated high cell viability (>90%), considerable adhesion, and extensive cytoskeletal organisation. Trilineage differentiation confirmed the multipotency of BMMSCs, with osteogenic, adipogenic, and chondrogenic markers being successfully expressed. BMMSCs and cMSCs exhibited enhanced differentiation and gene expression profiles. At week 4, key osteogenic and angiogenic genes such as BMP2, VEGFC, RUNX2, and COL1A1 showed elevated expression, indicating improved bone formation and vascularisation activity. Markers associated with extracellular matrix (ECM) remodelling, including MMP9 and TIMP1, were also upregulated, suggesting active tissue remodelling. ELISA analysis for VEGF further demonstrated increased VEGF secretion, highlighting the scaffold’s angiogenic potential. The improved cellular response and vascular signalling emphasise the translational relevance of laser-modified GreenBone scaffolds for bone tissue engineering, particularly for critical-sized defect repair requiring rapid vascularised bone regeneration. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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15 pages, 3247 KB

Open AccessEditor’s ChoiceArticle

RNA-Seq of Gingival Fibroblasts Grown on Collagen Membranes and Hyaluronic Acid

by Layla Panahipour, Xiaoyu Huang and Reinhard Gruber

J. Funct. Biomater. 2026, 17(2), 57; https://doi.org/10.3390/jfb17020057 - 23 Jan 2026

Viewed by 1428

Abstract

Purpose: Collagen membranes are widely used biomaterials in periodontal and implant dentistry and can be combined with hyaluronic acid (HA). Although collagen membranes are expected to exhibit bioactive properties and support fibroblast infiltration, their specific impact on fibroblast behavior remains unclear. Methods: To [...] Read more.

Purpose: Collagen membranes are widely used biomaterials in periodontal and implant dentistry and can be combined with hyaluronic acid (HA). Although collagen membranes are expected to exhibit bioactive properties and support fibroblast infiltration, their specific impact on fibroblast behavior remains unclear. Methods: To investigate this, human gingival fibroblasts were seeded on collagen matrices—mucoderm^®, a collagen fleece derived from dermis, and Jason^® membrane derived from pericardium—with or without lyophilized HA. Subsequent bulk RNA sequencing was used to assess transcriptional responses. Results: Both mucoderm^® and the collagen fleece caused significant transcriptional changes compared with fibroblasts grown on standard tissue culture surfaces and Jason^® membrane. These changes included upregulation of CEMIP, STC1, and TM4SF1, and downregulation of ADM2, PSAT1, and GPR1. Notably, the collagen fleece increased expression of extracellular matrix-related genes including CCN1, CCN2, COL1A1, POSTN, SPARC, TAGLN, FBN2, CCDC80, and CREB3L1 relative to mucoderm^®. Additionally, the expression of proteases MMP3 and MMP10, along with detoxification-related genes MT1E, MT2A, HMOX1, and NQO1, was relatively decreased. HA coating elevated IL24 expression in mucoderm^®, but no similar effect was observed in the collagen fleece. Conclusions: These findings demonstrate that collagen membranes can influence the transcriptome of gingival fibroblasts and suggest that collagen fleece has a stronger effect on extracellular matrix formation than mucoderm^®. Furthermore, HA coating does not consistently alter fibroblast responses. Full article

(This article belongs to the Special Issue Role of Dental Biomaterials in Promoting Oral Health)

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23 pages, 3161 KB

Open AccessEditor’s ChoiceArticle

Antimicrobial Activity of Acidifying Hyaluronic Acid–Starch Microfiber Dressings Against Clinical Isolates from Chronic Wounds

by Ivana Stará, Petra Moťková, Markéta Vydržalová, Marcela Pejchalová, Ladislav Burgert, Radim Hrdina, Marek Bouška, Martin Adam, Karel Královec and Iveta Brožková

J. Funct. Biomater. 2026, 17(2), 58; https://doi.org/10.3390/jfb17020058 - 23 Jan 2026

Viewed by 902

Abstract

Hyaluronic acid (HA) is a natural biopolymer widely used in wound dressings for its supportive role in the healing process. In this study, we investigated the occurrence of microorganisms in chronic wounds and evaluated the antimicrobial activity of newly synthesized HA–Starch-based materials enriched [...] Read more.

Hyaluronic acid (HA) is a natural biopolymer widely used in wound dressings for its supportive role in the healing process. In this study, we investigated the occurrence of microorganisms in chronic wounds and evaluated the antimicrobial activity of newly synthesized HA–Starch-based materials enriched with acidifying agents. Microbial isolates obtained from chronic wounds were tested for susceptibility using the agar diffusion method. The prepared materials exhibited significant antimicrobial activity against both reference strains and multidrug-resistant clinical isolates. Further characterization by scanning electron microscopy and elemental analysis confirmed uniform microfiber morphology and the expected elemental composition of the fibers. Cytotoxicity assessments performed using the xCELLigence system demonstrated the potential safety of developed materials. Overall, the results indicate that HA–Starch-based materials containing acidifying compounds exhibit strong in vitro antimicrobial activity against chronic-wound isolates, supporting their potential for further evaluation in wound care applications. Full article

(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)

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38 pages, 4278 KB

Open AccessEditor’s ChoiceReview

Fibrous Biomaterial Scaffold for Tympanic Membrane Repair: Microarchitectural Engineering and Structure Function Performance

by Lea Jiang, Chokri Cherif and Michael Wöltje

J. Funct. Biomater. 2026, 17(1), 53; https://doi.org/10.3390/jfb17010053 - 21 Jan 2026

Cited by 2 | Viewed by 1554

Abstract

Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they [...] Read more.

Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they come with well-known limitations. Beyond the need for additional harvesting procedures, these grafts rarely reproduce the intricate, fibrous layering of the native TM, which can compromise sound transmission after healing. In search of alternatives, fibre-based scaffolds have attracted considerable interest. The primary advantage of this material is the level of structural control it affords. The fibre orientation, porosity, and overall microarchitecture can be adjusted to replicate the organisation and mechanical behaviour of the natural membrane. A range of biocompatible polymers—among them silk fibroin, poly(ε-caprolactone), poly(lactic acid), and poly(vinyl alcohol) and their composites—provide options for tuning stiffness, degradation rates, and interactions with cells, making them suitable building blocks for TM repair constructs. This review provides a comprehensive overview of contemporary fabrication methodologies, namely electrospinning, additive manufacturing, melt electrowriting, and hybrid strategies. In addition, it offers a detailed discussion of the evaluation procedures employed for these scaffolds and discusses how scaffold structure affects later performance. Mechanical testing, microstructural imaging, and in vitro biocompatibility assays help to determine how closely a construct can approach the performance of the native tissue. Bringing these elements together may support the gradual translation of fibre-based TM scaffolds into clinical practice. Full article

(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)

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17 pages, 7685 KB

Open AccessEditor’s ChoiceArticle

Biomechanical Stimulation of Mesenchymal Stem Cells in 3D Peptide Nanofibers for Bone Differentiation

by Faye Fouladgar, Robert Powell, Emily Carney, Andrea Escobar Martinez, Amir Jafari and Neda Habibi

J. Funct. Biomater. 2026, 17(1), 52; https://doi.org/10.3390/jfb17010052 - 19 Jan 2026

Cited by 1 | Viewed by 1226

Abstract

Mechanical stimulation critically regulates mesenchymal stem cell (MSC) differentiation, yet its effects in three-dimensional (3D) environments remain poorly defined. Here, we developed a custom dynamic stretcher integrating poly(dimethylsiloxane) (PDMS) chambers to apply cyclic strain to human MSCs encapsulated in Fmoc-diphenylalanine (Fmoc-FF) peptide hydrogels—a [...] Read more.

Mechanical stimulation critically regulates mesenchymal stem cell (MSC) differentiation, yet its effects in three-dimensional (3D) environments remain poorly defined. Here, we developed a custom dynamic stretcher integrating poly(dimethylsiloxane) (PDMS) chambers to apply cyclic strain to human MSCs encapsulated in Fmoc-diphenylalanine (Fmoc-FF) peptide hydrogels—a fully synthetic, tunable extracellular matrix mimic. Finite element modeling verified uniform strain transmission across the hydrogel. Dynamic stretching at 0.5 Hz and 10% strain induced pronounced cytoskeletal alignment, enhanced actin stress fiber formation (coherency index

\approx 0.85

), and significantly increased proliferation compared to static or high-frequency (2.5 Hz, 1%) conditions (coherency index

\approx 0.6

). Quantitative image analysis confirmed strain-dependent increases in coherency index and F-actin intensity, indicating enhanced mechanotransductive remodeling. Biochemical assays and qRT–PCR revealed 2–3-fold upregulation of osteogenic markers—RUNX2, ALP, COL1A1, OSX, BMP, ON, and IBSP—under optimal strain. These results demonstrate that low-frequency, high-strain mechanical loading in 3D peptide hydrogels activates RhoA/ROCK and YAP/TAZ pathways, driving osteogenic differentiation. The integrated experimental–computational approach provides a robust platform for studying mechanobiological regulation and advancing mechanically tunable biomaterials for bone tissue engineering. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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24 pages, 3309 KB

Open AccessEditor’s ChoiceReview

Biomaterials for Improving Skin Penetration in Treatment of Skin Cancer

by Davide Secci, Andrew Urquhart, Vasileios Bekiaris and Katrine Qvortrup

J. Funct. Biomater. 2026, 17(1), 39; https://doi.org/10.3390/jfb17010039 - 15 Jan 2026

Cited by 3 | Viewed by 1928

Abstract

Skin cancer is among the most common malignancies worldwide, posing a significant societal burden due to its increasing incidence and its limited responsiveness to conventional topical therapies. Treatment is challenged by the presence of the skin barrier which restricts drug penetration. This review [...] Read more.

Skin cancer is among the most common malignancies worldwide, posing a significant societal burden due to its increasing incidence and its limited responsiveness to conventional topical therapies. Treatment is challenged by the presence of the skin barrier which restricts drug penetration. This review discusses the structural and physiological challenges of topical delivery and summarizes efforts to develop functional biomaterials to enhance skin drug penetration. Important aspects to consider when developing formulation strategies, such as drug properties and release mechanisms, are discussed alongside current limitations and future perspectives. Full article

(This article belongs to the Special Issue Review Papers in Biomaterials for Cancer Therapies)

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28 pages, 1711 KB

Open AccessEditor’s ChoiceReview

Advanced Biomaterials for Craniofacial Tissue Regeneration: From Fundamental Mechanism to Translational Applications—A Scoping Review

by Żaneta Anna Mierzejewska, Valentina Veselinović, Nataša Trtić, Saša Marin, Jan Borys and Bożena Antonowicz

J. Funct. Biomater. 2026, 17(1), 44; https://doi.org/10.3390/jfb17010044 - 15 Jan 2026

Cited by 9 | Viewed by 1974

Abstract

Recent advances in biomaterials, immunomodulation, stem cell therapy, and biofabrication are reshaping maxillofacial surgery, shifting reconstruction paradigms toward biologically integrated and patient-specific tissue regeneration. This review provides a comprehensive synthesis of current and emerging strategies for bone and soft-tissue regeneration in the craniofacial [...] Read more.

Recent advances in biomaterials, immunomodulation, stem cell therapy, and biofabrication are reshaping maxillofacial surgery, shifting reconstruction paradigms toward biologically integrated and patient-specific tissue regeneration. This review provides a comprehensive synthesis of current and emerging strategies for bone and soft-tissue regeneration in the craniofacial region, with particular emphasis on bioactive ceramics, biodegradable polymers, hybrid composites, and stimuli-responsive smart materials. We further examine translational technologies such as extracellular vesicles, decellularized extracellular matrices, organoids, and 3D bioprinting, highlighting key challenges such as bioink standardization, perfusion limitations, and regulatory classification. Maxillofacial surgery is positioned for a paradigm shift toward personalized, biologically active, and clinically scalable regenerative solutions. Full article

(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration (2nd Edition))

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37 pages, 2140 KB

Open AccessEditor’s ChoiceReview

Functional Peptide-Based Biomaterials for Pharmaceutical Application: Sequences, Mechanisms, and Optimization Strategies

by Dedong Yu, Nari Han, Hyejeong Son, Sun Jo Kim and Seho Kweon

J. Funct. Biomater. 2026, 17(1), 37; https://doi.org/10.3390/jfb17010037 - 13 Jan 2026

Cited by 7 | Viewed by 2985

Abstract

Peptide-based biomaterials have emerged as versatile tools for pharmaceutical drug delivery due to their biocompatibility and tunable sequences, yet a comprehensive overview of their categories, mechanisms, and optimization strategies remains lacking to guide clinical translation. This review systematically collates advances in peptide-based biomaterials, [...] Read more.

Peptide-based biomaterials have emerged as versatile tools for pharmaceutical drug delivery due to their biocompatibility and tunable sequences, yet a comprehensive overview of their categories, mechanisms, and optimization strategies remains lacking to guide clinical translation. This review systematically collates advances in peptide-based biomaterials, covering peptide excipients (cell penetrating peptides, tight junction modulating peptides, and peptide surfactants/stabilizers), self-assembling peptides (peptide-based nanospheres, cyclic peptide nanotubes, nanovesicles and micelles, peptide-based hydrogels and depots), and peptide linkers (for antibody drug-conjugates, peptide drug-conjugates, and prodrugs). We also dissect sequence-based optimization strategies, including rational design and biophysical optimization (cyclization, stapling, D-amino acid incorporation), functional motif integration, and combinatorial discovery with AI assistance, with examples spanning marketed drugs and research-stage candidates. The review reveals that cell-penetrating peptides enable efficient intracellular payload delivery via direct penetration or endocytosis; self-assembling peptides form diverse nanostructures for controlled release; and peptide linkers achieve site-specific drug release by responding to tumor-associated enzymes or pH cues, while sequence optimization enhances stability and targeting. Peptide-based biomaterials offer precise, biocompatible and tunable solutions for drug delivery, future advancements relying on AI-driven design and multi-functional modification will accelerate their transition from basic research to clinical application. Full article

(This article belongs to the Special Issue Peptides with a Rationale: Smart Biomaterials for Biomedical Innovation)

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18 pages, 2377 KB

Open AccessEditor’s ChoiceArticle

Photo Crosslinkable Hybrid Hydrogels for High Fidelity Direct Write 3D Printing: Rheology, Curing Kinetics, and Bio-Scaffold Fabrication

by Riley Rohauer, Kory Schimmelpfennig, Perrin Woods, Rokeya Sarah, Ahasan Habib and Christopher L. Lewis

J. Funct. Biomater. 2026, 17(1), 30; https://doi.org/10.3390/jfb17010030 - 4 Jan 2026

Cited by 2 | Viewed by 1567

Abstract

This work characterizes hybrid hydrogels prepared via the combination of natural and synthetic polymers. By incorporating a biocompatible compound, poly(ethylene glycol) diacrylate (PEGDA, M_n = 400), into alginate and carboxymethyl cellulose (CMC)-based hydrogels, the in situ UV crosslinking of these materials was [...] Read more.

This work characterizes hybrid hydrogels prepared via the combination of natural and synthetic polymers. By incorporating a biocompatible compound, poly(ethylene glycol) diacrylate (PEGDA, M_n = 400), into alginate and carboxymethyl cellulose (CMC)-based hydrogels, the in situ UV crosslinking of these materials was assessed. A custom direct-write (DW) 3D bioprinter was utilized to prepare hybrid hydrogel constructs and scaffolds. A control sample, which consisted of 4% w/v alginate and 4% w/v CMC, was prepared and evaluated in addition to three PEGDA (4.5, 6.5, and 10% w/v)-containing hybrid hydrogels. Rotational rheology was utilized to evaluate the thixotropic behavior of these materials. Filament fusion tests were employed to generate bilayer constructs of various pore sizes, providing metrics for the printability and diffusion rate of hydrogels post-extrusion. Printability indicates the shape fidelity of pore geometry, whereas diffusion rate represents material spreading after deposition. Curing kinetics of PEGDA-containing hydrogels were evaluated using photo-Differential Scanning Calorimetry (DSC) and photorheology. The Kamal model was fitted to photo-DSC results, enabling an assessment and comparison of the curing kinetics for PEGDA-containing hydrogels. Photorheological results highlight the increase in hydrogel stiffness concomitant with PEGDA content. The range of obtained complex moduli (G*) provides utility for the development of brain, kidney, and heart tissue (620–4600 Pa). The in situ UV irradiation of PEGDA-containing hydrogels improved the shape fidelity of printed bilayers and decreased filament diffusion rates. In situ UV irradiation enabled 10-layer scaffolds with 1 × 1 mm pore sizes to be printed. Ultimately, this study highlights the utility of PEGDA-containing hybrid hydrogels for high-resolution DW 3D bioprinting and potential application toward customizable tissue analogs. Full article

(This article belongs to the Special Issue 3D Bioprinting for Tissue Engineering and Regenerative Medicine)

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17 pages, 4506 KB

Open AccessEditor’s ChoiceArticle

3D Printing of Oxygen-Sensing ECM-Based Skin Graft for Personalized Treatment of Chronic Wounds—A Technological Proof of Concept

by Yehonatan Zur, Rotem Hayam, Nir Almog, Inna Kovrigina, Limor Baruch, Aharon Blank and Marcelle Machluf

J. Funct. Biomater. 2026, 17(1), 28; https://doi.org/10.3390/jfb17010028 - 1 Jan 2026

Viewed by 1674

Abstract

Chronic diabetic wounds are often characterized by persistent hypoxia and poor healing outcomes, highlighting the need for regenerative grafts that not only promote tissue repair but also provide insights into the wound microenvironment. In this study, we introduce a novel strategy for diabetic [...] Read more.

Chronic diabetic wounds are often characterized by persistent hypoxia and poor healing outcomes, highlighting the need for regenerative grafts that not only promote tissue repair but also provide insights into the wound microenvironment. In this study, we introduce a novel strategy for diabetic ulcer treatment through the development of a structurally personalized skin graft. The graft is fabricated via 3D bioprinting of natural porcine skin extracellular matrix (psECM) and integrated with microsensors for oxygen monitoring. We established a porcine skin decellularization protocol that efficiently removed cellular components, while preserving the integrity of the ECM, as verified by DNA quantification and scanning electron microscopy. The resulting psECM bioink demonstrated rheological properties suitable for 3D printing, which depended on psECM concentration and exhibited temperature-responsive gelation behavior. Incorporation of LiNC-BuO oxygen microsensors into the bioink enabled real-time, non-invasive oxygen level monitoring within the printed constructs. Both in vitro and in vivo studies confirmed the cytocompatibility and low immunogenicity of the psECM-based grafts with embedded microsensors. Moreover, the 3D bioprinting technology enabled the manufacturing of grafts tailored to match individual wound geometries. The technological proof of concept presented herein for this multifunctional platform, which integrates the regenerative benefits of ECM scaffolds with advanced biosensing capabilities, represents a promising approach for enhancing future therapeutic outcomes in the management of diabetic ulcers. Full article

(This article belongs to the Special Issue Biomaterials: Functionalization, Diagnostics, and Modeling for Advanced Therapeutic and Regenerative Applications)

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18 pages, 3870 KB

Open AccessEditor’s ChoiceArticle

Nanotherapy Targeting miR-10b Improves Survival in Orthotopic Glioblastoma Models

by Bryan D. Kim, Ming Chen, Sujan K. Mondal, Elizabeth Kenyon, Christiane L. Mallett, Ana deCarvalho, Zdravka Medarova and Anna Moore

J. Funct. Biomater. 2026, 17(1), 15; https://doi.org/10.3390/jfb17010015 - 26 Dec 2025

Cited by 2 | Viewed by 1381

Abstract

Glioblastoma (GBM) is the most aggressive primary cancer with poor survival. In the absence of an effective treatment and a high probability of recurrence, new therapeutic approaches are urgently needed. This study focused on targeting microRNA-10b (miR-10b) highly expressed in GBM cells that [...] Read more.

Glioblastoma (GBM) is the most aggressive primary cancer with poor survival. In the absence of an effective treatment and a high probability of recurrence, new therapeutic approaches are urgently needed. This study focused on targeting microRNA-10b (miR-10b) highly expressed in GBM cells that has been identified as one of the key drivers of GBM progression. Inhibiting miR-10b using antisense oligonucleotides (ASOs) has shown promise, but its delivery is challenging due to short circulation half-life, degradation by nucleases, and limited blood–brain barrier (BBB) permeability. To overcome these barriers, we employed a magnetic nanoparticle (MN) platform to deliver anti-miR-10b ASOs (MN-anti-miR10b). In addition to serving as a delivery vehicle, these nanoparticles can be used for monitoring delivery using magnetic resonance imaging (MRI). In therapeutic studies in orthotopic models of GBM presented here we used MN-anti-miR10b as well as TTX-MC138, a clinically tested anti-miR10b nanotherapeutic now in Phase I trials in patients with solid (non-GBM) cancers. Both formulations showed efficient delivery, as demonstrated by imaging and improved survival, leading to target inhibition and increased apoptosis. This approach may offer a novel strategy for delivering therapeutics to GBM and improving patient outcomes in one of the most aggressive and treatment-resistant forms of brain cancer. Full article

(This article belongs to the Special Issue Functional Nanomaterials for Gene Therapy)

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36 pages, 7024 KB

Open AccessEditor’s ChoiceArticle

Multilayer Ti–Cu Oxide Coatings on Ti6Al4V: Balancing Antibacterial Activity, Mechanical Strength, Corrosion Resistance, and Cytocompatibility

by Stefan Valkov, Maria P. Nikolova, Tanya V. Dimitrova, Maria Elena Stancheva, Dimitar Dechev, Nikolay Ivanov, Yordan Handzhiyski, Andreana Andreeva, Maria Ormanova, Angel Anchev and Margarita D. Apostolova

J. Funct. Biomater. 2026, 17(1), 16; https://doi.org/10.3390/jfb17010016 - 26 Dec 2025

Cited by 1 | Viewed by 1790

Abstract

Titanium alloys are widely used for biomedical implants, but their performance is limited by wear, corrosion, and susceptibility to bacterial colonisation. To overcome these drawbacks, multilayer Ti–Cu oxide coatings were deposited on Ti6Al4V substrates using direct current magnetron sputtering. Two multilayer architectures (6 [...] Read more.

Titanium alloys are widely used for biomedical implants, but their performance is limited by wear, corrosion, and susceptibility to bacterial colonisation. To overcome these drawbacks, multilayer Ti–Cu oxide coatings were deposited on Ti6Al4V substrates using direct current magnetron sputtering. Two multilayer architectures (6 × 2 and 12 × 2 TiO₂/CuO bilayers) were fabricated and evaluated for their structural, mechanical, electrochemical, and biological properties. SEM/EDS and XRD confirmed well-adhered crystalline coatings consisting of rutile/anatase TiO₂ and monoclinic CuO with uniform elemental distribution. The coatings increased surface roughness, improved adhesion, and enhanced hardness by up to ~180% compared to uncoated Ti6Al4V alloy. Compared to the bare substrate, electrochemical testing in simulated body fluid showed higher corrosion resistance of both coated samples, but particularly for the 12 × 2 multilayers. Both architectures provided sustained Cu²⁺ release over seven days without a burst effect. In vitro biological testing showed that both multilayer coatings achieved over 96% inhibition of Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis, while exhibiting moderate antibacterial effects against Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa). Despite the presence of copper, MG-63 osteoblast-like cells demonstrated sustained viability and successful extracellular matrix mineralisation, indicating excellent cytocompatibility of the coatings with bone-forming cells. These results demonstrate that multilayer Ti–Cu oxide coatings can effectively balance antibacterial performance, corrosion resistance, mechanical strength, and support bone cell integration, making them a promising strategy for the surface modification of titanium-based biomedical implants. Full article

(This article belongs to the Special Issue Design and Synthesis Composites for Biomedical Application)

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14 pages, 551 KB

Open AccessEditor’s ChoiceSystematic Review

Mechanistic Advancements and Translational Progress in Hyaluronic Acid-Based Scaffolds and Conduits for Peripheral Nerve Regeneration

by Caroline J. Cushman, Naveen A. Sakthiyendran, Maryam Salimi, Evan J. Hernandez, Ruthvik Allala, Tammam Hanna, Anceslo Idicula and Brendan J. MacKay

J. Funct. Biomater. 2026, 17(1), 14; https://doi.org/10.3390/jfb17010014 - 25 Dec 2025

Viewed by 1538

Abstract

Peripheral nerve injuries often recover poorly. Hyaluronic acid (HA) biomaterials, with regenerative and anti-fibrotic properties, may augment repair. We performed a PRISMA-guided systematic review of PubMed, Scopus, Web of Science, and Embase (January 2000–August 2024), capturing in vitro, in vivo, and clinical investigations [...] Read more.

Peripheral nerve injuries often recover poorly. Hyaluronic acid (HA) biomaterials, with regenerative and anti-fibrotic properties, may augment repair. We performed a PRISMA-guided systematic review of PubMed, Scopus, Web of Science, and Embase (January 2000–August 2024), capturing in vitro, in vivo, and clinical investigations of HA in peripheral nerve repair; data on study context, interventions, and outcomes were extracted. Screening and extraction were performed in duplicate. Forty-eight studies met inclusion criteria. Across in vitro and in vivo models, HA-based biomaterials consistently reduced perineural fibrosis, enhanced axonal regeneration, and improved SFI, CMAP, and NCV compared with conventional repair. Several HA hydrogels and composite conduits achieved functional outcomes approaching autografts, particularly when combined with exosomes, neurotrophic factors, or mechanobiologically tuned scaffolds. Early clinical studies demonstrated safety but remain limited by size and short follow-up. Overall, HA-containing biomaterials appear anti-fibrotic, neuroprotective, and pro-regenerative, supporting their promise as adjuncts for peripheral nerve reconstruction. For this to translate into clinical practice, future work should standardize formulations and dosing, employ rigorous, clinically relevant animal models with long-term endpoints, and advance well-powered, controlled trials to test effectiveness and durability in patients. Clinically, HA platforms show promise as anti-adhesion barriers after neurolysis and as biofunctional fillers/coatings for nerve conduits, but standardized formulations and adequately powered trials are needed to define indications and dosing. Full article

(This article belongs to the Special Issue Biomaterials for Nerve Repair and Regeneration: Spearheading Translational Impacts in Nerve Injury)

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49 pages, 5540 KB

Open AccessEditor’s ChoiceReview

Recent Advances in Silk Fibroin Derived from Bombyx mori for Regenerative Medicine

by Yuhao Zhang and Iman Roohani

J. Funct. Biomater. 2026, 17(1), 12; https://doi.org/10.3390/jfb17010012 - 24 Dec 2025

Cited by 6 | Viewed by 3379

Abstract

Bombyx mori silk fibroin (BMSF) has developed from a textile fibre into a mature biomaterial with broad utility in regenerative medicine, owing to its unique hierarchical molecular structure. Its excellent biocompatibility, tuneable mechanical properties, optical property, and controllable biodegradability arise from its protein [...] Read more.

Bombyx mori silk fibroin (BMSF) has developed from a textile fibre into a mature biomaterial with broad utility in regenerative medicine, owing to its unique hierarchical molecular structure. Its excellent biocompatibility, tuneable mechanical properties, optical property, and controllable biodegradability arise from its protein conformation, which can be precisely regulated through processing and fabrication strategies. Recent advances in bioengineering have further expanded the capabilities of BMSF, enabling the development of biomaterials with engineered architectures, tailored microtopographies, and enhanced bioactivity. These technological developments have facilitated the design of scaffolds that more effectively guide tissue regeneration and enhance functional outcomes. Such constructs have demonstrated promising outcomes in the regeneration of bone, cartilage, vascular, neural, corneal, and skin tissues. This review summarises current progress while emphasising emerging trends that couple BMSF’s unique molecular features with immune-responsive design, instructive microarchitectures that guide cell behaviour, composite scaffold design, and functionalisation with bioactive molecules. BMSF has been positioned as a structurally adaptable and biologically instructive platform whose continued progression will depend on integrating advanced fabrication, mechanistic understanding, and translational standardisation. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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18 pages, 920 KB

Open AccessEditor’s ChoiceReview

Application of Amorphous Nanomaterials in Dentistry: A Comprehensive Review

by Iris Xiaoxue Yin, John Yun Niu, Veena Wenqing Xu, Ollie Yiru Yu, Irene Shuping Zhao and Chun Hung Chu

J. Funct. Biomater. 2026, 17(1), 11; https://doi.org/10.3390/jfb17010011 - 23 Dec 2025

Cited by 1 | Viewed by 1351

Abstract

Conventional dental materials with organised crystal structures exhibit limitations in corrosion resistance, bioactivity, and drug delivery capability. In contrast, amorphous nanomaterials offer potential advantages in overcoming these limitations due to their unique structural properties. They are characterised by a non-crystalline, disordered atomic structure [...] Read more.

Conventional dental materials with organised crystal structures exhibit limitations in corrosion resistance, bioactivity, and drug delivery capability. In contrast, amorphous nanomaterials offer potential advantages in overcoming these limitations due to their unique structural properties. They are characterised by a non-crystalline, disordered atomic structure and are similar to a solidified liquid at the nanoscale. Among the amorphous nanomaterials used in dentistry, there are five major categories: calcium-, silicon-, magnesium-, zirconia-, and polymer-based systems. This study reviewed these amorphous nanomaterials by investigating their synthesis, properties, applications, limitations, and future directions in dentistry. These amorphous nanomaterials are synthesised primarily through low-temperature methods, including sol–gel processes, rapid precipitation, and electrochemical etching, which prevent atomic arrangements into crystalline structures. The resulting disordered atomic configuration confers exceptional properties, including enhanced solubility, superior drug-loading capacity, high surface reactivity, and controlled biodegradability. These characteristics enable diverse dental applications. Calcium-based amorphous nanomaterials, particularly amorphous calcium phosphate, demonstrate the ability to remineralise tooth enamel. Silicon-based amorphous nanomaterials function as carriers that can release antibacterial agents in response to stimuli. Magnesium-based amorphous nanomaterials are antibacterial and support natural bone regeneration. Zirconia-based amorphous nanomaterials strengthen the mechanical properties of restorative materials. Polymer-based amorphous nanomaterials enable controlled release of medications over extended periods. Despite the advances in these amorphous nanomaterials, there are limitations regarding material stability over time, precise control of degradation rates in the oral environment, and the development of reliable large-scale manufacturing processes. Researchers are creating smart materials that respond to specific oral conditions and developing hybrid systems that combine the strengths of different nanomaterials. In summary, amorphous nanomaterials hold great promise for advancing dental treatments through their unique properties and versatile applications. Clinically, these materials could improve the durability, bioactivity, and targeted drug delivery in dental restorations and therapies, leading to better patient outcomes. Full article

(This article belongs to the Special Issue Biomaterials in Dentistry: Current Status and Advances)

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17 pages, 7531 KB

Open AccessEditor’s ChoiceArticle

L-Serine–Incorporated Collagen Scaffolds for Modulating In Vivo Degradation Behavior

by Su-Young Kim, Ji-Hyeon Oh, Min-Ho Hong, Joon Ha Lee, You-Young Jo and Seong-Gon Kim

J. Funct. Biomater. 2025, 16(12), 466; https://doi.org/10.3390/jfb16120466 - 18 Dec 2025

Cited by 1 | Viewed by 1080

Abstract

Collagen-based biomaterials are widely used, but their relatively rapid biodegradation can limit functional duration. Such collagen constructs are widely used as barrier membranes in guided tissue and bone regeneration, where controlled degradation is essential for maintaining function. Although conventional crosslinking methods extend stability, [...] Read more.

Collagen-based biomaterials are widely used, but their relatively rapid biodegradation can limit functional duration. Such collagen constructs are widely used as barrier membranes in guided tissue and bone regeneration, where controlled degradation is essential for maintaining function. Although conventional crosslinking methods extend stability, they may introduce cytotoxicity, alter mechanical behavior, or hinder tissue integration. This study evaluated whether incorporating L-serine, a polar amino acid capable of hydrogen bonding, could modulate collagen structure and slow degradation without chemical crosslinking. L-Serine was selected because its hydroxyl-containing side chain can engage in biocompatible, hydrogen-bond–mediated interactions that offer a mild, non-crosslinking means of stabilizing collagen. Collagen scaffolds, prepared by incorporating L-serine into a collagen hydrogel followed by drying, were produced with 0–40 wt% L-serine and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, circular dichroism, and scanning electron microscopy. In vivo degradation was assessed in a subcutaneous mouse model comparing unmodified collagen, collagen containing 40 wt% L-serine, and a commercially available bilayer porcine collagen membrane (Bio-Gide^®, composed of type I and III collagen), with residual area quantified by serial sonography and histological evaluation. Low-to-moderate L-serine incorporation preserved triple-helical features, while 40 wt% led to crystalline domain formation and β-sheet enrichment. L-serine–treated collagen exhibited significantly greater residual area (2.70 ± 1.45 mm²) than unmodified collagen (0.37 ± 0.22 mm², p < 0.05), although Bio-Gide^® remained the most persistent (5.64 ± 2.76 mm²). These findings demonstrate that L-serine incorporation can modulate collagen structure and degradation kinetics through a simple, aqueous, and non-crosslinking approach. The results provide preliminary feasibility data supporting amino acid–assisted tuning of collagen resorption properties and justify further evaluation using membrane-specific fabrication and application-relevant testing. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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15 pages, 2354 KB

Open AccessEditor’s ChoiceArticle

3D-Printed Multifunctional Multicompartment Polymer-Based Capsules for Tunable and Spatially Controlled Drug Release

by Antonio Minopoli, Giordano Perini, Davide Evangelista, Matteo Marras, Alberto Augello, Valentina Palmieri, Marco De Spirito and Massimiliano Papi

J. Funct. Biomater. 2025, 16(12), 456; https://doi.org/10.3390/jfb16120456 - 8 Dec 2025

Viewed by 1450

Abstract

The development of polymer-based systems is central to the design of next-generation drug delivery carriers, as polymers enable versatile tuning of physicochemical properties and responsiveness. In this work, we introduce a 3D printing-based strategy for the fabrication of multicompartment capsules that integrate multiple [...] Read more.

The development of polymer-based systems is central to the design of next-generation drug delivery carriers, as polymers enable versatile tuning of physicochemical properties and responsiveness. In this work, we introduce a 3D printing-based strategy for the fabrication of multicompartment capsules that integrate multiple polymers within a unique one-step process. This approach allows precise spatial organization and structural complexity, yielding capsules with customizable features such as compartmentalization, polymer-specific responsiveness, and localized release control. In particular, pH-triggered release can be programmed across distinct polymeric regions of the capsules, enabling site-specific delivery along different intestinal segments, including the small intestine and colon. The use of 3D printing thus provides a scalable and adaptable platform to generate multifunctional polymer-based carriers with finely tunable drug release profiles, paving the way for new directions in polymer-enabled controlled delivery technologies. Full article

(This article belongs to the Special Issue Polymer-Based Materials in Biomedical Applications)

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16 pages, 1608 KB

Open AccessEditor’s ChoiceArticle

Injectable Piezoelectric Hydrogel for Vital Pulp Therapy

by Varun Solanki, Carolina Montoya, Prasanna Neelakantan, Maobin Yang and Santiago Orrego

J. Funct. Biomater. 2025, 16(12), 452; https://doi.org/10.3390/jfb16120452 - 5 Dec 2025

Cited by 1 | Viewed by 2182

Abstract

Vital pulp therapy (VPT) seeks to preserve pulp vitality by using biocompatible with regenerative potential. This study tested the hypothesis that an injectable gelatin methacryloyl (GelMA) hydrogel containing piezoelectric barium titanate promotes odontogenic differentiation of dental pulp stem cells (DPSC) significantly better than [...] Read more.

Vital pulp therapy (VPT) seeks to preserve pulp vitality by using biocompatible with regenerative potential. This study tested the hypothesis that an injectable gelatin methacryloyl (GelMA) hydrogel containing piezoelectric barium titanate promotes odontogenic differentiation of dental pulp stem cells (DPSC) significantly better than a commercially available tricalcium silicate material used for vital pulp therapy. First, the light-curable, injectable piezoelectric hydrogel was engineered and characterized for its physicomechanical, piezoelectric properties and biocompatibility to DPSCs. The effect of this gel on the odontogenic differentiation of DPSCs was determined by measuring the expression level of key genes, compared to Biodentine XP. The hydrogel exhibited excellent injectability (<1 kgf of force), mechanical stability, and generated physiologically relevant voltages under cyclic loading mimicking mastication. MTT and ROS assays show no cytotoxic or damaging oxidative stress effects. When DPSCs were cultured over the materials under cyclic loading, the piezoelectric hydrogel significantly enhanced cell viability and upregulated COL1A1, DSPP, and DMP1 expression compared to Biodentine XP and non-piezoelectric hydrogel controls. These findings establish piezoelectric hydrogel as a self-powered, bioactive platform that converts physiological forces into regenerative bioelectric cues, offering a promising next-generation material for vital pulp therapy. Full article

(This article belongs to the Special Issue Advanced Biomaterials and Engineered Systems in Endodontics)

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12 pages, 1447 KB

Open AccessEditor’s ChoiceArticle

Three-Dimensional Bioprinting of Regenerative Cartilage Constructs with Directional Ionically Derived Stiffness Gradients

by Maryam Hosseini, Angeliki Dimaraki, Gerjo. J. V. M. van Osch, Lidy E. Fratila-Apachitei, Pedro J. Díaz-Payno and Amir A. Zadpoor

J. Funct. Biomater. 2025, 16(12), 451; https://doi.org/10.3390/jfb16120451 - 3 Dec 2025

Cited by 3 | Viewed by 3158

Abstract

Tissue engineering approaches for cartilage tissue regeneration are expanding to include the complex features of the tissue, such as the biological and mechanical gradients. Many of these approaches are, however, based on the use of multiple biomaterials or concentrations, and crosslinking methods that [...] Read more.

Tissue engineering approaches for cartilage tissue regeneration are expanding to include the complex features of the tissue, such as the biological and mechanical gradients. Many of these approaches are, however, based on the use of multiple biomaterials or concentrations, and crosslinking methods that make it difficult to integrate and control the properties of the resulting scaffolds. In this study, a 3D bioprinted scaffold with a stiffness gradient was fabricated by using a single biomaterial type and concentration combined with a directional ionic crosslinking method. The scaffolds revealed a gradient in stiffness from 39.8 ± 6.6 kPa at the top to 60.6 ± 10.9 kPa at the bottom of the scaffolds. Live/dead analysis of human chondrocytes embedded in the scaffolds showed no negative effects of the stiffness gradient on cell viability over 28 days. The induced stiffness gradient led to a gradient in cell density and sulfated glycosaminoglycan deposition in the bioprinted tissue constructs with enhanced values in the softer top region of the scaffolds as compared to the stiffer bottom part. This study showed a novel method to generate scaffolds with stiffness gradients from a single biomaterial and indicates that such scaffolds could be used to spatially regulate the behavior of chondrocytes and the associated deposition of the cartilage matrix. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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28 pages, 18645 KB

Open AccessEditor’s ChoiceArticle

Biomimetic Glycosaminoglycan-Enriched Electrospun Polymeric Scaffolds for Enhanced Early Tissue Regeneration

by Morgane Meyer, Rana Smaida, Henri Favreau, Cristina Yus, Hervé Gegout, Manuel Arruebo, Nadia Bahlouli, Guy Ladam, Guillaume Conzatti, Stephan Lemmens, Guoqiang Hua, Florence Fioretti and Nadia Benkirane-Jessel

J. Funct. Biomater. 2025, 16(12), 447; https://doi.org/10.3390/jfb16120447 - 29 Nov 2025

Viewed by 1367

Abstract

Implantable scaffolds are increasingly recognized as transformative tools in regenerative medicine, offering the potential to prevent or mitigate tissue degeneration. Osteoarthritis is a widespread degenerative joint disease that often progresses from early focal lesions to severe joint damage, creating substantial clinical and socioeconomic [...] Read more.

Implantable scaffolds are increasingly recognized as transformative tools in regenerative medicine, offering the potential to prevent or mitigate tissue degeneration. Osteoarthritis is a widespread degenerative joint disease that often progresses from early focal lesions to severe joint damage, creating substantial clinical and socioeconomic burdens. Preventive strategies for early-stage lesions remain limited. This study reports the design and development of a functional polymeric scaffold intended to support early tissue regeneration and potentially prevent lesion progression. The scaffold consists of an electrospun poly (ε-caprolactone) nanofibrous membrane enriched with glycosaminoglycans, including hyaluronic acid and chondroitin sulfate, to mimic essential features of the cartilage extracellular matrix and provide a supportive microenvironment. Complete structural, physicochemical, and mechanical characterization was performed to assess the scaffold architecture, stability, hydration properties, and suitability for tissue environments. In vitro investigations were conducted to evaluate cytocompatibility and the interaction of the scaffold with relevant cell types. The scaffold is designed as a potential future preventive strategy to support cartilage integrity and limit disease progression. This approach represents a promising strategy to preserve joint integrity and function, addressing a critical unmet clinical need and enabling translation toward clinical application. Full article

(This article belongs to the Special Issue Materials and Techniques for Bone Tissue Engineering: From Scaffolds to Complex Matrices)

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24 pages, 1622 KB

Open AccessEditor’s ChoiceReview

An Overview of 3D Bioprinting Impact on Cell Viability: From Damage Assessment to Protection Solutions

by Sara Manzoli, Elena Merotto, Martina Piccoli, Pierangelo Gobbo, Silvia Todros and Piero G. Pavan

J. Funct. Biomater. 2025, 16(12), 436; https://doi.org/10.3390/jfb16120436 - 25 Nov 2025

Cited by 11 | Viewed by 3529

Abstract

Three-dimensional (3D) bioprinting has become a widely exploited tissue engineering technique for producing functional constructs that can mimic and replace native tissues. To this end, different printing strategies can be adopted, including inkjet-based, light-assisted, and extrusion-based bioprinting. Despite the great improvements that these [...] Read more.

Three-dimensional (3D) bioprinting has become a widely exploited tissue engineering technique for producing functional constructs that can mimic and replace native tissues. To this end, different printing strategies can be adopted, including inkjet-based, light-assisted, and extrusion-based bioprinting. Despite the great improvements that these innovative techniques introduce, cell viability maintenance during and after the bioprinting process remains a challenging open question. Indeed, the reduction in cell viability is generally related to several crucial conditions during printing, such as high shear stresses and a nutrient-deficient environment of printed constructs. In this work, the current literature on 3D bioprinting technologies is reviewed, focusing on the level of cell damage that can be imparted during biomaterial printing. In particular, extrusion bioprinting, extrusion-associated shear stress and its impact on cell viability are described in detail. The simulation of the bioprinting process through computational fluid dynamics is proposed as an appropriate method to analyze the parameters involved during bioprinting. Moreover, the viability of cells encapsulated into bioink is discussed, as well as literature techniques aimed at enhancing it by both biomaterial modifications and cell micro-encapsulation. Full article

(This article belongs to the Special Issue 3D Bioprinting for Tissue Engineering and Regenerative Medicine)

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29 pages, 5971 KB

Open AccessEditor’s ChoiceReview

The Ballet of Natural-Product: Carrier-Free “Triadic” Drug Delivery Platforms for Enhanced Tumor Treatment

by Liyan Yang and Zhonglei Wang

J. Funct. Biomater. 2025, 16(12), 433; https://doi.org/10.3390/jfb16120433 - 25 Nov 2025

Cited by 2 | Viewed by 2043

Abstract

Cancer poses a considerable challenge to global public health and stands as the second leading cause of mortality worldwide. Chemotherapy provides limited benefits for advanced-stage cancer, mainly due to high systemic toxicity and drug resistance. Optimal cancer treatment requires a sophisticated, multidisciplinary collaboration [...] Read more.

Cancer poses a considerable challenge to global public health and stands as the second leading cause of mortality worldwide. Chemotherapy provides limited benefits for advanced-stage cancer, mainly due to high systemic toxicity and drug resistance. Optimal cancer treatment requires a sophisticated, multidisciplinary collaboration aimed at extending survival, enhancing quality of life, and reducing toxicity. Natural products present advantages, including a wide array of structural diversity, reduced toxicity, improved immune modulation, and the ability to act on multiple targets. Nanomedicine design shows promise in tumor treatment and diagnosis by improving efficacy and minimizing side effects. Due to the heterogeneity of tumors in genetics, metabolism, and microenvironment, natural product-based carrier-free drug delivery platforms have been actively investigated and demonstrated considerable potential for enhanced tumor treatment. “Triadic” strategies can simultaneously perform various functions on a carrier-free intelligent nanoplatform. These include combinational chemotherapy, photodynamic therapy (PDT) with bioimaging and chemotherapy, PDT combined with photothermal therapy (PTT) and chemotherapy, chemo-radio-theranostics, as well as gene therapy (GT) in conjunction with PTT and chemotherapy. This multifaceted approach enhances therapeutic efficacy, reduces multidrug resistance, and minimizes systemic toxicity. This review encompasses recent advancements in cancer therapy using carrier-free “triadic” nanomedicines based on natural products (between 2024 and 2025) and evaluates this evolving field, emphasizing the pivotal role of natural products—berberine, camptothecin, hypericin, erianin, curcumin, lactose, paclitaxel, gambogic acid, and glycyrrhizic acid—in drug delivery platforms. Furthermore, it addresses the challenges and bottlenecks encountered by carrier-free drug delivery platforms, offering valuable insights into their development trajectories. Full article

(This article belongs to the Special Issue 15th Anniversary of JFB—Advanced Biomaterials for Drug Delivery)

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19 pages, 7795 KB

Open AccessEditor’s ChoiceArticle

Endothelial Cells Differentiated from Human Induced Pluripotent Stem Cells Form Aligned Network Structures in Engineered Neural Tissue

by Poppy O. Smith, Parmjit Jat and James B. Phillips

J. Funct. Biomater. 2025, 16(11), 425; https://doi.org/10.3390/jfb16110425 - 20 Nov 2025

Viewed by 1789

Abstract

Background/Objectives: Endothelial cells play a key role in peripheral nerve regeneration, forming aligned vasculature which bridges the gap in the injured nerve tissue and guides the regrowing tissue. This work aimed to mimic key features of this aligned vasculature by differentiating endothelial cells [...] Read more.

Background/Objectives: Endothelial cells play a key role in peripheral nerve regeneration, forming aligned vasculature which bridges the gap in the injured nerve tissue and guides the regrowing tissue. This work aimed to mimic key features of this aligned vasculature by differentiating endothelial cells from human induced pluripotent stem cells (hiPSCs) and incorporating them into engineered neural tissue (EngNT). Methods: hiPSCs were differentiated into endothelial cells with the temporal addition of growth factors and biomolecules. These hiPSC-derived endothelial cells (hiPSC-ECs) were incorporated into EngNT fabricated from collagen hydrogels using the gel aspiration-ejection (GAE) technique and maintained in vitro to allow endothelial network formation. Results: At the mRNA and protein level, pluripotency marker expression decreased and endothelial cell marker expression increased over the course of hiPSC differentiation to endothelial cells. The derived endothelial cells expressed CD31, CD144, ENG, VEGFR2, and VWF, and formed network structures in the matrix tubulogenesis assay. hiPSC-ECs incorporated into EngNT were viable and aligned. They formed highly aligned tube-like structures containing lumens after four days in culture and the EngNT constructs supported neurite growth in vitro when co-cultured with rat dorsal root ganglion (DRG) neurons. Conclusions: This work rapidly generated engineered nerve tissue containing highly aligned endothelial tube-like structures, resembling key features of the early nerve regeneration bridge. Therefore, this 3D engineered tissue provides a platform to study the effects of endothelial cell structures in nerve repair treatment and translational development. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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32 pages, 19195 KB

Open AccessEditor’s ChoiceArticle

Suitability of Mg-Nd and Mg-Zn Alloys to Obtain Biodegradable Structures for Bone Defects

by Veronica Manescu (Paltanea), Aurora Antoniac, Maria Cristina Moraru, Iulian Antoniac, Cosmin Mihai Cotrut, Sebastian Gradinaru, Alexandra Iulia Dreanca, Bogdan Sevastre, Romelia Pop, Flaviu Alexandru Tabaran, George Mihail Vlasceanu, Mariana Ionita and Marius Manole

J. Funct. Biomater. 2025, 16(11), 423; https://doi.org/10.3390/jfb16110423 - 12 Nov 2025

Cited by 3 | Viewed by 2060

Abstract

Mg-based alloys are one of the most promising materials used in regenerative medicine for bone tissue engineering. Considering the increasing prevalence of a continuously aging population, as well as the high incidence of accidents and bone cancers, it is crucial to explore biomaterials [...] Read more.

Mg-based alloys are one of the most promising materials used in regenerative medicine for bone tissue engineering. Considering the increasing prevalence of a continuously aging population, as well as the high incidence of accidents and bone cancers, it is crucial to explore biomaterials that can serve as bone substitutes. After carefully analyzing the literature in the introduction section, we proposed two Mg-based alloys as suitable for obtaining biodegradable structures for bone defect treatment. To achieve trustworthy results, the alloys’ microstructure was investigated using microscopic techniques coupled with energy-dispersive spectroscopy and X-ray diffraction. The obtained results were comparable with those described in references on similar Mg alloys. Then, the mechanical compression properties were highlighted, and the in vitro corrosion behavior proved that Mg-Zn exhibited a reduced corrosion rate compared to the Mg-Nd alloy, as tested using electrochemical methods. However, the in vivo tests showed good biocompatibility for both magnesium alloys. In conclusion, both alloys are suitable for use as potential bone substitute applications, but it must be taken into consideration that Mg-Zn alloys present lower biodegradation and mechanical properties. For future investigations, we aim to develop bone substitutes made from these materials, specifically designed for small bone defect treatment and with patient-adapted geometry. Due to the differences mentioned above, various designs will be tested. Full article

(This article belongs to the Special Issue The 15th Anniversary of JFB—Functional Biomaterials: Bioactive Properties and Medical Applications)

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55 pages, 17120 KB

Open AccessEditor’s ChoiceReview

Magnetic Hydrogels as a Treatment for Oncological Pathologies

by Veronica Manescu (Paltanea), Adrian-Vasile Dumitru, Aurora Antoniac, Iulian Antoniac, Gheorghe Paltanea, Elena-Cristina Zeca (Berbecar), Mirela Gherghe, Iosif Vasile Nemoianu, Alexandru Streza, Costel Paun and Sebastian Gradinaru

J. Funct. Biomater. 2025, 16(11), 414; https://doi.org/10.3390/jfb16110414 - 5 Nov 2025

Cited by 2 | Viewed by 2765

Abstract

Cancer is considered today as a prevalent research direction due to the fact that, by 2050, more than 30 million cases will occur, followed by about 19 million deaths. It is expected that scholars will search for new, innovative, and localized therapies to [...] Read more.

Cancer is considered today as a prevalent research direction due to the fact that, by 2050, more than 30 million cases will occur, followed by about 19 million deaths. It is expected that scholars will search for new, innovative, and localized therapies to ensure a much more targeted treatment with reduced side effects. Magnetic hydrogels overcome the disadvantages of classical magnetic nanoparticles in various oncological domains, including magnetic hyperthermia, theragnostic, immunotherapy, and, notably, regenerative medicine and contrast substances. We will review the magnetic hydrogel topics that may be involved as a potential application for cancer. Firstly, we present the international context and subject importance in the framework of statistics estimated by some researchers. Then, the magnetic hydrogel synthesis method will be briefly described with examples extracted from the literature. Supplementary, we will emphasize the main attributes of an ideal magnetic hydrogel, and last but not least, we will review some of the latest in vitro and in vivo studies in a direct relationship with magnetic hyperthermia, chemotherapeutic drug release dynamics, and immunotherapy used as single strategies or in combination, by underling the magnetic properties of the hydrogels and importance of application of magnetic fields. We will conclude our review paper by discussing toxicity issues, future trends, limitations, and proposed new approaches to address them. Full article

(This article belongs to the Special Issue Advances in Multifunctional Hydrogels for Biomedical Application (2nd Edition))

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16 pages, 10746 KB

Open AccessEditor’s ChoiceArticle

Pre-Vascularized 3-Dimensional Skin Substitutes Promote Angiogenesis and Tissue Repair in a Murine Model of Refractory Skin Ulcers

by Shota Tojo, Hiromi Miyazaki, Takami Saiki, Yasuyuki Tsunoi, Shingo Nakamura and Ryuichi Azuma

J. Funct. Biomater. 2025, 16(11), 409; https://doi.org/10.3390/jfb16110409 - 3 Nov 2025

Cited by 2 | Viewed by 1741

Abstract

Restoring blood flow is crucial for treating refractory ulcers. Despite advancements in various biomaterials, none incorporating pre-formed blood vessels have been commercialized. To address this, we developed a pre-vascularized three-dimensional (3D) skin substitute (PV-3D skin) designed to enhance healing when treating refractory ulcers. [...] Read more.

Restoring blood flow is crucial for treating refractory ulcers. Despite advancements in various biomaterials, none incorporating pre-formed blood vessels have been commercialized. To address this, we developed a pre-vascularized three-dimensional (3D) skin substitute (PV-3D skin) designed to enhance healing when treating refractory ulcers. This study aimed to evaluate the therapeutic role of PV-3D skin transplantation in refractory ulcer models, induced by applying mitomycin C to wounds in severe immunodeficient mice. The wounds were then treated with PV-3D skin, non-vascularized 3D skin, skin grafts, or wound dressings. The PV-3D skin group demonstrated healing dynamics comparable to those of the skin graft group, with similar tissue morphology and wound temperature changes. Furthermore, at day 7 post-transplantation, the PV-3D skin group demonstrated significantly higher hypoxia-inducible factor 1-alpha expression levels compared to the 3D skin group. By day 14, the PV-3D skin group exhibited a significantly larger vascular area compared to the 3D skin group. Notably, PV-3D skin treatment stimulated host-derived angiogenesis, thereby enhancing wound healing and reducing the recurrence of refractory ulcers. These results suggest that PV-3D skin transplantation offers a promising therapeutic approach for refractory ulcers, especially in terms of angiogenesis. Full article

(This article belongs to the Special Issue The 15th Anniversary of JFB—Functional Biomaterials: Bioactive Properties and Medical Applications)

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23 pages, 7319 KB

Open AccessEditor’s ChoiceArticle

Corrosion-Modulating Effect of Pharmaceutical Agents in a Hybrid Coating System on Pure Magnesium

by Lara Moreno, Adrián Belarra-Rodriguez, Marta Mohedano, Laura Castro, Margarita Chevalier, Raul Arrabal and Endzhe Matykina

J. Funct. Biomater. 2025, 16(11), 406; https://doi.org/10.3390/jfb16110406 - 30 Oct 2025

Cited by 1 | Viewed by 1576

Abstract

There is a knowledge gap about the effect of pharmaceutical agents on the biodegradation of Mg-based resorbable implants. The present work investigates how three common antibiotics and three anti-inflammatory drugs affect the corrosion of high-purity Mg, with and without ceramic and hybrid ceramic/polymeric [...] Read more.

There is a knowledge gap about the effect of pharmaceutical agents on the biodegradation of Mg-based resorbable implants. The present work investigates how three common antibiotics and three anti-inflammatory drugs affect the corrosion of high-purity Mg, with and without ceramic and hybrid ceramic/polymeric coatings, using electrochemical impedance spectroscopy and hydrogen evolution tests. A Ca-P-Si-based ceramic coating is developed using plasma electrolytic oxidation (PEO), after the AC voltage and frequency parameters are optimized. A hybrid coating included a PEO and a poly(ε-caprolactone) (PCL) top layer formed by dip coating. High-purity Mg exhibited an instantaneous onset of corrosion with a corrosion rate of 90 μm/year after 24 h of immersion in a modified α-MEM. A hybrid PEO/PCL coating prevents the onset of corrosion for at least 5 h and reduces the H₂ evolution during the following 90 h by two times by the precipitation of 5–40 μm thick Ca-P surface deposits. Gentamicin, naproxen, streptomycin, ciprofloxacin and paracetamol were found to be corrosion accelerators with respect to bare h.p. Mg, whereas aspirin was found to be an inhibitor. Streptomycin-functionalized PEO/PCL system exhibited an active protection mechanism, triggered upon the release of the coating and substrate cations, associated with the coating defect-blocking action of the insoluble Me(II)-streptomycin chelates. Full article

(This article belongs to the Section Biomaterials for Drug Delivery)

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25 pages, 7146 KB

Open AccessEditor’s ChoiceArticle

Biopolymer Fibers of High Strength and Enhanced Orientation by the Synergy of High/Low Molecular Weight Chitosans in Hybrid Biomaterials Processed by Gel Spinning

by Tuan Anh Tran, Ingo Doench, Arnaud Kamdem Tamo, Shaghayegh Jahangir, Sofia Marquez-Bravo, Pamela Molina, Martin Helmstaedter, Aliuska Morales Helguera, Christian Gorzelanny and Anayancy Osorio-Madrazo

J. Funct. Biomater. 2025, 16(11), 405; https://doi.org/10.3390/jfb16110405 - 29 Oct 2025

Viewed by 1808

Abstract

High-performance spun bionanocomposite fibers, composed of high-molecular-weight chitosan (HMW), low-molecular-weight chitosan “oligomers” (LMW), and cellulose nanofibers (CNFs), were successfully fabricated via gel spinning of viscous aqueous chitosan (CHI) based formulations into a NaOH coagulation bath. The X-ray diffraction (XRD) analysis revealed that the [...] Read more.

High-performance spun bionanocomposite fibers, composed of high-molecular-weight chitosan (HMW), low-molecular-weight chitosan “oligomers” (LMW), and cellulose nanofibers (CNFs), were successfully fabricated via gel spinning of viscous aqueous chitosan (CHI) based formulations into a NaOH coagulation bath. The X-ray diffraction (XRD) analysis revealed that the incorporation of cellulose nanofibers contributed to enhance crystallinity of chitosan in spun fibers. The spinning process, which comprised sequential acidic solubilization, basic neutralization, stretching, and drying steps, produced chitosan/CNF composite fibers with high crystallinity, further enhanced by the incorporation of low molecular weight chitosan. The cellulose nanofibers seem to promote CHI crystallization, by acting as nucleation sites for the nucleation and growth of chitosan crystals, with those latter of LMW further enhancing crystallization and orientation due to higher mobility of shorter polymer chains. Two-dimensional XRD patterns demonstrated the preferential alignment of both CNFs and chitosan crystals along the fiber axis. Increasing the proportion of short-chain chitosan led to a reduction of the viscosity of collodion, facilitating the spinning of solutions with higher polymer concentrations. The X-ray diffraction (XRD) analysis revealed that the addition of low-molecular-weight chitosan (LMW), with an intermediate molecular weight Mw of ~4.4 × 10⁴ g/mol, produced the most significant improvements in the crystallinity index (CrI) and orientation. This structural enhancement corresponded to superior mechanical properties like Young’s modulus, yield stress σ_y, and stress-at-break σ_b of the processed composite fibers. By incorporating that intermediate molecular weight chitosan, a Young’s modulus as high as 20 GPa was achieved for the spun composite fibers, which was twice higher than the modulus of around 10 GPa obtained by adding the lowest molecular weight chitosan of Mw ~ 2.9 × 10⁴ g/mol in the composite, and largely above the modulus of around 5 GPa obtained for fiber just spun with chitosan without incorporation of cellulose nanofibers. Full article

(This article belongs to the Section Synthesis of Biomaterials via Advanced Technologies)

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31 pages, 3096 KB

Open AccessEditor’s ChoiceReview

Implications of Tissue Engineering for Tendon Repair and Regeneration

by Dana Ivanisova, Katarina Bevizova, Sara Vach Agocsova, Lubos Danisovic and Martina Culenova

J. Funct. Biomater. 2025, 16(11), 403; https://doi.org/10.3390/jfb16110403 - 28 Oct 2025

Cited by 4 | Viewed by 6563

Abstract

Tendon injuries affect millions of people globally and are among the most prevalent musculoskeletal conditions, frequently resulting in chronic pain, reduced mobility, and functional impairment. While conservative and surgical treatments are available, limitations such as low healing capacity, scar formation, and reduced biomechanics [...] Read more.

Tendon injuries affect millions of people globally and are among the most prevalent musculoskeletal conditions, frequently resulting in chronic pain, reduced mobility, and functional impairment. While conservative and surgical treatments are available, limitations such as low healing capacity, scar formation, and reduced biomechanics necessitate alternative approaches. Tissue engineering offers a promising solution by combining cells, scaffolds, and bioactive molecules to regenerate tendon tissue. This review presents key concepts and emerging trends, highlighting the cellular components, scaffold materials, and manufacturing processes. Tenocytes and mesenchymal stem cells are fundamental for tissue regeneration, as they synthesize extracellular matrix components and regulate inflammatory responses. Various natural and synthetic polymers have been fabricated into scaffolds that mimic the structure and biomechanics of natural tendons. Composite and hybrid scaffolds are utilized to improve the biocompatibility of natural materials with the mechanical stability of synthetic materials. Advanced technologies, such as electrospinning, freeze-drying, and 3D bioprinting, enable the creation of scaffolds with defined architecture and functional gradients, improving cell alignment, differentiation, and tendon–bone integration. Although promising preclinical data exists, major challenges remain in translating these strategies clinically, particularly vascularization, immune rejection, and mechanical stability. Continued interdisciplinary attempts in biomaterials science, cellular biology, and engineering are crucial to advancing clinically viable tendon tissue engineering. Full article

(This article belongs to the Special Issue Materials and Techniques for Bone Tissue Engineering: From Scaffolds to Complex Matrices)

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31 pages, 12238 KB

Open AccessEditor’s ChoiceArticle

Micropatterning and Nanodropletting of Titanium by Shifted Surface Laser Texturing Significantly Enhances In Vitro Osteogenesis of Healthy and Osteoporotic Mesenchymal Stromal Cells

by Theresia Stich, Francisca Alagboso, Girish Pattappa, Jin Chu, Denys Moskal, Michal Povolný, Maximilian Saller, Veronika Schönitzer, Konstantin J. Scholz, Fabian Cieplik, Volker Alt, Maximilian Rudert, Tomáš Kovářík, Tomáš Křenek and Denitsa Docheva

J. Funct. Biomater. 2025, 16(11), 401; https://doi.org/10.3390/jfb16110401 - 27 Oct 2025

Cited by 2 | Viewed by 2325

Abstract

The key to proper implant integration in bone replacement is to orchestrate the complex interactions between materials and tissues. Moreover, due to the rapid demographic shift towards aging societies and the increase in elderly and osteoporotic patients, it is of great importance that [...] Read more.

The key to proper implant integration in bone replacement is to orchestrate the complex interactions between materials and tissues. Moreover, due to the rapid demographic shift towards aging societies and the increase in elderly and osteoporotic patients, it is of great importance that implant materials are osteointegrative in not only healthy but also compromised bone tissues. Here, titanium (Ti) scaffolds were subjected to shifted laser surface texturing (sLST) using a nanosecond pulsed laser to create an open pore macrotopography with micro-and nano-Ti droplets. In contrast to conventional laser texturing, which leads to high heat accumulation; in sLST, the frequency of laser pulses is low, allowing for resolidification, thereby creating a surface with abundant coverage micro-/nanodroplets. The main objective was to compare the cellular responses of human mesenchymal stromal cells (hMSCs) on sLST-textured Ti surfaces (LT-Ti) for the first time with standard sand-blasted, acid-etched surfaces (SLA-Ti). In-depth analyses of cell survival, proliferation, shape, mineralization, and gene expression were performed. Cell survival/proliferation was found to be similar on both surfaces; however, SEM imaging revealed differences in hMSC morphology. On LT-Ti, cells adopted well-rounded shapes, whereas on SLA-Ti they assumed more planar shapes. Bulk RNA sequencing performed after short-term culture on both surfaces disclosed expression changes in genes such as DUSP6, TNFSF12-TNFSF13 and SULT1A4. Remarkably, the osteogenic differentiation capacity of hMSCs was significantly enhanced on LT-Ti compared to SLA-Ti. Furthermore, aged/osteoporotic donor cohorts showed significantly enhanced matrix mineralization on LT-Ti. In conclusion, our novel results demonstrate that sLST-Ti surfaces are safe, highly biocompatible, can rescue patient-cohort-specific mineralization behavior, and therefore hold great potential for the development into next-generation implants, which are suitable for both the elderly and bone-compromised populations. Full article

(This article belongs to the Section Bone Biomaterials)

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21 pages, 3350 KB

Open AccessEditor’s ChoiceArticle

Multifunctional Peptide-Based Biohybrid for Targeted Reduction of Metastatic Breast Carcinoma-Associated Osteolysis

by Nicole Stadler, Bingjie Gao, Maria Jose Silva, Joscha Borho, Eva Haunschild, Kaloian Koynov, Melanie Haffner-Luntzer, Anita Ignatius, Gilbert Weidinger, Seah Ling Kuan, Tanja Weil and Holger Barth

J. Funct. Biomater. 2025, 16(11), 399; https://doi.org/10.3390/jfb16110399 - 25 Oct 2025

Viewed by 3956

Abstract

Metastatic breast carcinoma (BC) cells are prone to spreading in the bone microenvironment, leading to a vicious cycle between local osteoclast-mediated osteolysis and tumor progression. Therefore, the targeted pharmacological down-modulation of BC cell proliferation as well as osteoclast differentiation and hyperactivity might represent [...] Read more.

Metastatic breast carcinoma (BC) cells are prone to spreading in the bone microenvironment, leading to a vicious cycle between local osteoclast-mediated osteolysis and tumor progression. Therefore, the targeted pharmacological down-modulation of BC cell proliferation as well as osteoclast differentiation and hyperactivity might represent a promising treatment option. We developed a multifunctional peptide nanocarrier combining bioactive EPI-X4 peptides and the Rho-inhibiting C3bot enzyme from Clostridium botulinum. C3bot is preferentially internalized into the cytosol of monocytic cells, including osteoclasts, where it inhibits Rho-mediated signal transduction. However, Rho-mediated cellular processes like migration and cell division can also be inhibited in non-monocytic cells if C3bot is delivered into their cytosol by a nanocarrier. To accomplish this, we designed a supramolecular transporter where one molecule of biotinylated C3bot and three biotinylated entities of the human EPI-X4 peptide-derived CXCR4 antagonist JM173 are assembled on avidin as a central platform. This modular transport system (JM173)₃-Avi-C3 down-modulated osteoclast formation and hyperactivity and delivered the therapeutic cargo C3bot successfully into the cytosol of breast cancer cells, where it inhibited Rho. Full article

(This article belongs to the Special Issue Advanced Biomaterials in Cancer Therapeutics and Diagnosis)

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24 pages, 4267 KB

Open AccessEditor’s ChoiceArticle

“Attractive” Treatment for Abdominal Aortic Aneurysm Repair: Magnetic Localization of Silk-Iron Packaged Extracellular Vesicles

by Ande X. Marini, Kiran J. McLoughlin, Amanda R. Pellegrino, Golnaz N. Tomaraei, Bo Li, John A. Curci, Mostafa Bedewy, Justin S. Weinbaum and David A. Vorp

J. Funct. Biomater. 2025, 16(11), 395; https://doi.org/10.3390/jfb16110395 - 22 Oct 2025

Cited by 2 | Viewed by 2194

Abstract

Abdominal aortic aneurysm (AAA) is a dilatation of the distal aorta to a diameter of 50% or more of its normal size of about 2 cm. Risk of aortic rupture can be nearly eliminated with either open surgery or endovascular repair. Procedural risks [...] Read more.

Abdominal aortic aneurysm (AAA) is a dilatation of the distal aorta to a diameter of 50% or more of its normal size of about 2 cm. Risk of aortic rupture can be nearly eliminated with either open surgery or endovascular repair. Procedural risks limit the value of these interventions unless the diameter of the aneurysm has reached a critical threshold (established as 5.5 cm in men or 5.0 cm in women). Thus, patients are monitored until this threshold is reached. Approximately 80% of small AAA will grow and exceed the threshold, providing a therapeutic window for altering this natural history and reducing the risk of rupture. Previous work in our lab has utilized adipose-derived mesenchymal stem cells (ASCs) to treat AAA in vivo, preserving elastic fibers and slowing aneurysm expansion. This work sought to create a delivery system for therapeutic extracellular vesicles (ASC-EVs) secreted by ASCs. Our delivery system incorporated the biocompatibility of regenerated silk fibroin (RSF), the magnetic moveability of iron oxide nanoparticles (IONPs), and the regenerative nature of ASC-EVs to create silk-iron packaged extracellular vesicles (SIPEs). Using this system, we tested the ability to magnetically localize the SIPEs and release their encapsulated ASC-EVs to exert their regenerative effects in vitro. We were successful in magnetically localizing the SIPEs in vitro and silk-iron microparticles (SIMPs) in vivo and in detecting their releasates via flow cytometry and cellular uptake assays. However, while their releasates were detected, their biological effects were diminished compared to unencapsulated controls. Thus, additional optimization related to loading efficiency is needed. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering: Current Status and Advances)

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14 pages, 2210 KB

Open AccessEditor’s ChoiceArticle

Antibacterial PEEK-Ag Surfaces: Development and In Vitro Evaluation Against Staphylococcus aureus and Pseudomonas aeruginosa

by Flávio Rodrigues, Mariana Fernandes, Filipe Samuel Silva, Óscar Carvalho and Sara Madeira

J. Funct. Biomater. 2025, 16(10), 388; https://doi.org/10.3390/jfb16100388 - 16 Oct 2025

Viewed by 1422

Abstract

In the pursuit of addressing the persistent challenge of bacterial adhesion and biofilm formation in dental care, this study investigates the efficacy of electric current as an alternative strategy, specifically focusing on its application in dental contexts. Polyether ether ketone (PEEK), known for [...] Read more.

In the pursuit of addressing the persistent challenge of bacterial adhesion and biofilm formation in dental care, this study investigates the efficacy of electric current as an alternative strategy, specifically focusing on its application in dental contexts. Polyether ether ketone (PEEK), known for its excellent biocompatibility and resistance to bacterial plaque, was enhanced with conductive properties by incorporating silver (Ag), a well-known antibacterial material. Through systematic in vitro experiments, the effectiveness of alternating current (AC) and direct current (DC) in reducing bacterial proliferation was evaluated. The tests were conducted using two bacterial strains: the Gram-positive Staphylococcus aureus and the Gram-negative Pseudomonas aeruginosa. Various configurations, current parameters, and two different electrode configurations were assessed to determine their impact on bacterial reduction. A notable finding from this study is that alternating current (AC) demonstrates superior efficacy compared to direct current (DC). The more significant decrease in CFUs/mL for P. aeruginosa with AC was recorded at the current levels of 5 mA and 500 nA. In opposition, S. aureus exhibited the greatest reduction at 5 mA and 1 mA. This study highlights the potential of using electric current within specific intensity ranges as an alternative strategy to effectively mitigate bacterial challenges in dental care. Full article

(This article belongs to the Section Antibacterial Biomaterials)

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16 pages, 3494 KB

Open AccessEditor’s ChoiceArticle

Fibronectin- and Bioactive Glass-Modified Alginate Scaffolds Support Limited Primary Cell Proliferation In Vitro yet Demonstrate Effective Host Integration In Vivo

by Benedetta Guagnini, Andrea Mazzoleni, Adrien Moya, Arnaud Scherberich, Barbara Medagli, Ivan Martin, Davide Porrelli, Manuele G. Muraro and Gianluca Turco

J. Funct. Biomater. 2025, 16(10), 386; https://doi.org/10.3390/jfb16100386 - 15 Oct 2025

Cited by 3 | Viewed by 1714

Abstract

Alginate-hydroxyapatite (AL) scaffolds modified with fibronectin (FN) or bioactive glass (BGMS10) have recently been characterized for their physicochemical properties and proposed as promising candidates for bone regeneration. Here, we present their first systematic biological evaluation, focusing on adhesion, proliferation, osteogenic differentiation, and in [...] Read more.

Alginate-hydroxyapatite (AL) scaffolds modified with fibronectin (FN) or bioactive glass (BGMS10) have recently been characterized for their physicochemical properties and proposed as promising candidates for bone regeneration. Here, we present their first systematic biological evaluation, focusing on adhesion, proliferation, osteogenic differentiation, and in vivo host response. We compared FN-, BG-, and unmodified AL scaffolds using an immortalized mesenchymal stromal cell line (M-SOD) and primary human bone marrow-derived (BM-MSCs) and adipose-derived stromal cells (ASCs). FN scaffolds enhanced initial adhesion across all cell types and supported proliferation in M-SODs, but primary BM-MSCs and ASCs showed minimal expansion, regardless of scaffold type. BG scaffolds promoted expression of late-stage osteogenic markers in BM-MSCs, consistent with their ion release profile, but had limited impact on ASCs. In vivo subcutaneous implantation of acellular scaffolds in nude mice revealed robust host cell infiltration and extracellular matrix deposition across all scaffold types, confirming biocompatibility and integration. However, vascularization remained limited and did not differ substantially between formulations. Together, these findings highlight a critical discrepancy between immortalized and primary stromal cell responses to scaffold cues, underscoring the choice of cell source when evaluating the biocompatibility of a novel scaffold. At the same time, the effective in vivo integration observed across scaffold types emphasizes the importance of host tissue responses for translational evaluation of functional biomaterials. Full article

(This article belongs to the Special Issue Bone Tissue Engineering: Recent Advances and Translation to Clinical Application)

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29 pages, 2552 KB

Open AccessEditor’s ChoiceReview

Acellular Extracellular Matrix Scaffolds in Regenerative Medicine: Advances in Decellularization and Clinical Applications

by Caijun Jin, Xinrui Zhang, Yongxun Jin, Pham Ngoc Chien and Chan Yeong Heo

J. Funct. Biomater. 2025, 16(10), 383; https://doi.org/10.3390/jfb16100383 - 12 Oct 2025

Cited by 19 | Viewed by 6462

Abstract

Decellularized extracellular matrix (dECM) scaffolds preserve native tissue structure and biochemical cues while minimizing immune responses, creating biomimetic templates that promote cell integration and tissue remodeling. This review examines the current state of dECM research, encompassing decellularization methods, scaffold quality evaluation assays, and [...] Read more.

Decellularized extracellular matrix (dECM) scaffolds preserve native tissue structure and biochemical cues while minimizing immune responses, creating biomimetic templates that promote cell integration and tissue remodeling. This review examines the current state of dECM research, encompassing decellularization methods, scaffold quality evaluation assays, and tissue-specific applications across dermis, nerve, heart, lung, adipose, and placental ECMs. We analyze commercially available dECM products and ongoing clinical trials, while highlighting recent advances including 3D bioprinting and the integration of dECM with stem cells and growth factors. Despite these promising developments, several challenges continue to limit broader clinical translation: protocol standardization, residual immunogenicity, mechanical durability, and regulatory, manufacturing, and cost barriers. To address these limitations, we outline future directions focusing on patient-specific scaffolds, scalable bioprocessing, and integrated biofabrication strategies that will enable the development of safe and effective dECM-based therapies. Full article

(This article belongs to the Special Issue Advanced Functional Biomaterials in Regenerative Medicine)

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30 pages, 2277 KB

Open AccessEditor’s ChoiceReview

Bioengineered In Situ-Forming Hydrogels as Smart Drug Delivery Systems for Postoperative Breast Cancer Immunotherapy: From Material Innovation to Clinical Translation

by Yan Yan, Yiling Chen, Litao Huang, Menghan Cai, Xia Yin, Yi Zhun Zhu and Li Ye

J. Funct. Biomater. 2025, 16(10), 381; https://doi.org/10.3390/jfb16100381 - 10 Oct 2025

Cited by 9 | Viewed by 4554

Abstract

Local recurrence after breast cancer surgery presents a critical challenge, demanding novel local immunotherapies capable of eliminating residual disease while avoiding systemic toxicity. In situ-forming hydrogels, functionalized with bioactive cargoes, represent a promising platform for precise spatiotemporal drug delivery directly into the post-resection [...] Read more.

Local recurrence after breast cancer surgery presents a critical challenge, demanding novel local immunotherapies capable of eliminating residual disease while avoiding systemic toxicity. In situ-forming hydrogels, functionalized with bioactive cargoes, represent a promising platform for precise spatiotemporal drug delivery directly into the post-resection tumor microenvironment. This review comprehensively examines the core design principles governing these advanced materials, highlighting their biocompatibility, stimuli-responsive behavior, tunable mechanics for conforming to surgical cavity, and capacity for multifunctional integration. A key mechanism discussed is how this controlled release profile orchestrates a temporal progression from innate immune activation to robust adaptive immunity. Despite significant promise, translational success faces substantial hurdles, including efficacy validation, scalable manufacturing, regulatory pathway definition, and the lack of predictive biomarkers. Future research priorities include optimizing drug/antigen release kinetics, establishing standardized characterization methods for complex biohybrid systems, and designing adaptive clinical trials incorporating detailed immunomonitoring. By integrating functional biomaterials with immuno-oncology, in situ-forming hydrogels offer a paradigm-shifting approach for postoperative cancer treatment. This review provides a strategic roadmap to accelerate their translation from bench to bedside. Full article

(This article belongs to the Special Issue Biomaterials for Drug Delivery and Cancer Therapy)

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