Journal of Functional Biomaterials

17 pages, 9790 KB

Open AccessEditor’s ChoiceReview

Vein Graft Preservation During Coronary Artery Bypass Graft Surgery: Operative Techniques, Biomaterials and Advances from Tissue Engineering

by Benedetto Ferraresi, Antonio Nenna, Mohamad Jawabra, Diletta Corrado, Filippo Barberi, Carmelo Dominici, Giovanni Casali, Lucia Barbieri, Gabriele Tumminello, Stefano Carugo, Massimo Chello and Mario Lusini

J. Funct. Biomater. 2026, 17(6), 305; https://doi.org/10.3390/jfb17060305 - 20 Jun 2026

Viewed by 1340

Abstract

The failure of saphenous vein grafts following coronary artery bypass grafting (CABG) remains a significant issue, as it limits the durability of vein-based surgical revascularisation compared to arterial conduits. Venous graft disease is a dynamic process that begins early in the perioperative period [...] Read more.

The failure of saphenous vein grafts following coronary artery bypass grafting (CABG) remains a significant issue, as it limits the durability of vein-based surgical revascularisation compared to arterial conduits. Venous graft disease is a dynamic process that begins early in the perioperative period as a consequence of harvesting trauma, ex vivo preservation, and the sudden exposure of the conduit to the arterial haemodynamic environment. This narrative review summarises the available evidence on local graft protection strategies, focusing on intraoperative and perioperative approaches aimed at preserving endothelial integrity, attenuating initial inflammation, and limiting maladaptive remodelling. Specifically, the review analyses the role of endothelium-protective preservation solutions, external support devices, biodegradable drug-eluting biomaterials, and locally targeted RNA therapies. Preclinical and early clinical evidence suggests that local graft protection is biologically plausible and may reduce intimal hyperplasia, luminal irregularity and adverse graft remodelling. However, its impact on long-term clinical outcomes remains uncertain. An integrated approach combining harvest optimisation, conduit preservation, mechanical support, and local delivery of drugs or regulatory molecules may represent a promising framework for improving vein graft biology; however, its ability to translate into durable patency gains and improved clinical outcomes after CABG requires further clinical validation. Full article

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

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21 pages, 967 KB

Open AccessEditor’s ChoiceReview

Vitreous Substitutes in Vitreoretinal Surgery: From Native Vitreous Physiology to Bioengineered Experimental Replacements

by Alessandro Avitabile, Ludovica Cannizzaro and Dario Rusciano

J. Funct. Biomater. 2026, 17(6), 301; https://doi.org/10.3390/jfb17060301 - 17 Jun 2026

Viewed by 1131

Abstract

The vitreous body is not only a transparent filling material of the posterior segment; it is a soft, hydrated, and biologically active matrix that supports structural, optical, and biochemical homeostasis. Vitrectomy therefore leaves a functional deficit that current substitutes only partly address. Intraocular [...] Read more.

The vitreous body is not only a transparent filling material of the posterior segment; it is a soft, hydrated, and biologically active matrix that supports structural, optical, and biochemical homeostasis. Vitrectomy therefore leaves a functional deficit that current substitutes only partly address. Intraocular gases, silicone oils, and perfluorocarbon liquids remain essential surgical tools, but they mainly provide mechanical tamponade and do not reproduce native viscoelasticity, diffusion control, or protection against oxidative and inflammatory stress. This review considers vitreous replacement as a functional biomaterials challenge. We discuss native vitreous physiology, the limitations of present tamponade agents, and emerging bioengineered substitutes designed to create a more physiological intravitreal environment. Particular attention is given to hydrogel and polymer-based systems, especially hyaluronic acid-based and in situ crosslinked platforms, which are being developed to combine optical clarity, injectability, soft mechanical support, controlled degradation, and favorable tissue interaction. We also emphasize the need for standardized preclinical testing of swelling, enzymatic stability, drug diffusion, rheology, and long-term biocompatibility. Although next-generation materials may move the field beyond passive space filling, manufacturing reproducibility, regulatory validation, chronic safety, and cautious early-phase trials remain major translational barriers. Full article

(This article belongs to the Special Issue Biomedical Applications of Hydrogels: Current Status and Advances)

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17 pages, 5676 KB

Open AccessEditor’s ChoiceArticle

Development of a Scaffold from the Cob of Zea mays L. “Choclo” to Obtain an In Vitro Bone Tissue Model

by Rafael Carbajal-Valverde, Luz Pérez-Tulich, Franco Huaccha-Cáceres, Giulianna Travi-Antonio and Julio Valdivia-Silva

J. Funct. Biomater. 2026, 17(6), 267; https://doi.org/10.3390/jfb17060267 - 1 Jun 2026

Viewed by 1796

Abstract

The lack of accessible in vitro 3D bone tissue models puts developing countries at a disadvantage in terms of research capacity and healthcare access. In this study, a decellularized corn cob scaffold was functionalized with GTMAC by adding quaternary ammonium groups and coating [...] Read more.

The lack of accessible in vitro 3D bone tissue models puts developing countries at a disadvantage in terms of research capacity and healthcare access. In this study, a decellularized corn cob scaffold was functionalized with GTMAC by adding quaternary ammonium groups and coating it with an alginate–gelatin hydrogel to promote mesenchymal stem cell adhesion, offering a low-cost platform for bone disease modeling. Systematic characterization of the scaffold demonstrated that decellularization reduced DNA content by over 80%. Chemical treatment affected the mechanical properties of the matrix, while the hydrogel coating and the functionalized surface of the scaffold promoted cell adhesion and morphology comparable to that observed in 3D cell cultures. MTT analysis showed a subtle reduction in metabolic signal in functionalized scaffolds, which may reflect changes in cell distribution and adhesion within the 3D matrix rather than cytotoxic effects. Full article

(This article belongs to the Section Bone Biomaterials)

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16 pages, 680 KB

Open AccessEditor’s ChoiceSystematic Review

Clinical Outcomes of Immediate and Delayed Composite Restorations After Pulp Capping with Biodentine: A Systematic Literature Review

by Margarita Aleksiuk, Ana Kostenkova and Saulius Drukteinis

J. Funct. Biomater. 2026, 17(5), 241; https://doi.org/10.3390/jfb17050241 - 10 May 2026

Viewed by 1704

Abstract

Background: Biodentine is widely used in vital pulp therapy due to its bioactivity and biocompatibility. However, treatment success depends not only on the material but also on the restorative approach. Clinically, Biodentine may be used as a temporary bulk restoration before delayed placement [...] Read more.

Background: Biodentine is widely used in vital pulp therapy due to its bioactivity and biocompatibility. However, treatment success depends not only on the material but also on the restorative approach. Clinically, Biodentine may be used as a temporary bulk restoration before delayed placement of a composite or immediately covered with a definitive composite. Aim: To evaluate clinical outcomes reported for delayed composite placement after temporary Biodentine restoration and immediate composite restoration following Biodentine pulp capping in permanent teeth. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD420261325248). Searches were performed in multiple databases. Clinical studies on Biodentine pulp capping reporting outcomes for either delayed or immediate composite restoration were included. Study selection, data extraction, and quality assessment were performed by two reviewers using Joanna Briggs Institute tools. Fourteen studies (8 randomized controlled trials and 6 cohort studies) were included. Results: Considerable heterogeneity was observed in study design and clinical protocols. Most included studies evaluated one of the two strategies separately, so the review results could not be interpreted as a direct comparison. In direct pulp capping, success rates ranged from 74–100% (delayed) and 79–100% (immediate). In indirect pulp capping, success rates ranged from 77.8–88% (delayed) and 80–95.2% (immediate). Meta-analysis was not feasible. Conclusion: Based on low certainty of evidence, both strategies show favorable outcomes, but current evidence does not support the superiority of either approach. Further well-designed comparative studies are needed. Full article

(This article belongs to the Special Issue Advanced Materials for Clinical Endodontic Applications (3rd Edition))

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33 pages, 19233 KB

Open AccessEditor’s ChoiceArticle

Multifunctional Y₂O₃-Modified Borotellurite Bioactive Glasses for Bone Tissue Engineering Applications

by Esmanur Oruc Ulas, Bulent Aktas, Abuzer Acikgoz, Serife Yalcin, Hatice Gumushan Aktas, Ebru Uyar and Zeynep Celik

J. Funct. Biomater. 2026, 17(5), 240; https://doi.org/10.3390/jfb17050240 - 9 May 2026

Cited by 1 | Viewed by 1483

Abstract

Developing bioactive glasses that simultaneously provide mechanical reliability, cytocompatibility, controlled ion release, and antibacterial functionality remains a major challenge in bone tissue engineering. In this study, borotellurite-based bioactive glasses with the composition (45 − x)TeO₂–20Na₂O–10CaO–15P₂O₅–10B [...] Read more.

Developing bioactive glasses that simultaneously provide mechanical reliability, cytocompatibility, controlled ion release, and antibacterial functionality remains a major challenge in bone tissue engineering. In this study, borotellurite-based bioactive glasses with the composition (45 − x)TeO₂–20Na₂O–10CaO–15P₂O₅–10B₂O₃–xY₂O₃ (x = 0–7 mol.%) were designed to elucidate the role of Y₂O₃ in governing composition–structure–property relationships. Structural, thermal, mechanical, ion-release, bioactivity, cytocompatibility, cell-adhesion, and antibacterial properties were systematically evaluated, and the most promising composition was further modified by silver surface coating. Y₂O₃ incorporation markedly enhanced thermal stability, hardness, and fracture resistance, with hardness reaching 4.317 GPa at 7 mol.%, while the highest compressive strength was achieved at 1 mol.% Y₂O₃ (67.97 MPa). Importantly, Y₂O₃ regulated dissolution behavior and mitigated the severe long-term cytotoxicity of the undoped glass, maintaining all doped compositions above the ISO 10993-5 threshold after 30 days. Higher Y₂O₃ contents also promoted osteoblast adhesion and facilitated bioactive surface layer formation following SBF immersion. No detectable E. coli adhesion was observed, whereas the TBY3 composition exhibited the lowest S. aureus adhesion, further improved by silver coating. These results demonstrate Y₂O₃ as an effective multifunctional modifier for engineering mechanically robust, biologically favorable, and antibacterial borotellurite bioactive glasses for bone repair. Full article

(This article belongs to the Section Bone Biomaterials)

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23 pages, 1081 KB

Open AccessEditor’s ChoiceReview

Advanced Grafting Biomaterials and Technologies in Chronic Wound Care: Mechanisms, Clinical Outcomes, and Therapeutic Integration

by Albert D. Luong, Moorthy Maruthapandi and John H. T. Luong

J. Funct. Biomater. 2026, 17(5), 239; https://doi.org/10.3390/jfb17050239 - 9 May 2026

Viewed by 2027

Abstract

Chronic wounds remain a major clinical and economic burden due to persistent inflammation, impaired perfusion, microbial biofilms, and dysregulated immune responses that collectively stall epithelialization. Polymicrobial bacterial–fungal biofilms, including Candida species, further delay healing by sustaining inflammation and promoting treatment-resistant infection. Recent advances [...] Read more.

Chronic wounds remain a major clinical and economic burden due to persistent inflammation, impaired perfusion, microbial biofilms, and dysregulated immune responses that collectively stall epithelialization. Polymicrobial bacterial–fungal biofilms, including Candida species, further delay healing by sustaining inflammation and promoting treatment-resistant infection. Recent advances have accelerated the development of bioengineered skin substitutes, collagen matrices, and placental-derived grafts that modulate macrophage polarization, reactive oxygen species signaling, and extracellular matrix remodeling to restore tissue architecture and promote neovascularization. Their effectiveness, however, depends on integration within structured care pathways that emphasize debridement, moisture balance, and infection control. Artificial intelligence, three-dimensional bioprinting, flexible microelectronic sensors for real-time wound monitoring, and bioactive compounds derived from traditional Chinese medicine, are expanding the therapeutic landscape. Together, these innovations support a shift toward predictive, personalized, and regenerative wound-care strategies. This review aims to provide a mechanistic and clinically contextualized overview of advanced grafting biomaterials, highlighting current applications, limitations, and future directions in chronic wound care. Full article

(This article belongs to the Special Issue Biomaterials, Bioconjugated Materials, and Biomaterial Composites with Antimicrobial Properties)

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16 pages, 3087 KB

Open AccessEditor’s ChoiceArticle

The Potential of a Graphene Monolayer in Macrophage Polarization Using RAW 264.7 Cells

by Iwona Lasocka, Karolina Gregorczyk-Zboroch, Aleksandra Krajewska, Ewa Skibniewska, Michał Skibniewski and Lidia Szulc-Dąbrowska

J. Funct. Biomater. 2026, 17(5), 232; https://doi.org/10.3390/jfb17050232 - 7 May 2026

Viewed by 1886

Abstract

Maintaining an appropriate balance of macrophage subpopulations throughout the wound healing process, using a graphene monolayer as a substrate, may represent a promising therapeutic strategy. In this study, the effect of a graphene monolayer on the polarization of RAW 264.7 macrophages was investigated [...] Read more.

Maintaining an appropriate balance of macrophage subpopulations throughout the wound healing process, using a graphene monolayer as a substrate, may represent a promising therapeutic strategy. In this study, the effect of a graphene monolayer on the polarization of RAW 264.7 macrophages was investigated using flow cytometry, fluorescence microscopy, and ELISA. Analysis of surface M1 (MHC II, CD80, CD86) and M2 (CD163, CD200R, CD206) markers demonstrated generally higher expression of M1 markers in M1-polarized groups (control, CM1; and graphene monolayer, GM1) compared to M2-polarized groups (CM2 and GM2), likely as a result of LPS and IFN-γ stimulation. Culturing macrophages on a graphene monolayer as a substrate for LPS- and IFN-γ-stimulated cells was associated with a trend toward reduced expression of all analyzed M1-associated markers compared with the control M1 group; however, this effect did not reach statistical significance. TNF-α secretion was higher in GM1 compared to CM0, GM0, and CM2. In contrast, surface markers alone were less conclusive for identifying M2 polarization, whereas intracellular markers such as ARG1 provided a more robust indication of the M2 phenotype. ARG1 expression was significantly elevated in CM2 and GM2 groups, with GM2 showing a significant increase relative to the control groups (CM0, CM1) and GM0 and GM1. These findings further support ARG1 and NOS2 as reliable markers of M2 and M1 polarization, respectively. The graphene monolayer did not induce spontaneous macrophage polarization. Only under M1 (LPS and IFN-γ) and M2 (IL-4 and IL-13) stimulation did it show a consistent trend toward modest modulation of macrophage polarization, possibly creating conditions conducive to tissue healing. Full article

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

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22 pages, 15964 KB

Open AccessEditor’s ChoiceArticle

Cryogenic Foaming of Silk Fibroin Composite for Scaffolds in Bone and Periodontal Regeneration

by Giuseppe De Giorgio, Barbara Medagli, Biagio Matera, Katia Rupel, Giuseppe Tarabella, Gianluca Turco, Maddalena Manfredi, Benedetta Ghezzi and Pasquale D’Angelo

J. Funct. Biomater. 2026, 17(5), 230; https://doi.org/10.3390/jfb17050230 - 6 May 2026

Viewed by 1966

Abstract

Bone tissue has a remarkable regenerative capacity; however, advanced strategies are needed to support the repair process for critical-sized defects. While autografts and allografts remain the gold standard, their limitations have stimulated alternative approaches in bone tissue engineering, in search of scaffolds capable [...] Read more.

Bone tissue has a remarkable regenerative capacity; however, advanced strategies are needed to support the repair process for critical-sized defects. While autografts and allografts remain the gold standard, their limitations have stimulated alternative approaches in bone tissue engineering, in search of scaffolds capable of mimicking native bone properties to promote effective regeneration. In this study, silk fibroin (SF)-based composite scaffolds incorporating β-tricalcium phosphate (β-TCP) and poly-ε-caprolactone (PCL) were synthesized using a simple and innovative cryogenic foaming method. The proposed fabrication technique overcomes many limitations of current synthesis methods, such as long processing times, the use of solvents, and reliance on complex, energy-intensive equipment. The composites were characterized using infrared spectroscopy to confirm the incorporation of all three components and their chemical bond arrangements. µ-CT, SEM, and ESEM analyses revealed that SF/β-TCP/PCL scaffolds exhibited great porosity and dynamic interaction with water while preserving pore morphology in wet environments. Swelling behavior, indirect cytotoxicity, and cell proliferation tests recognized the greater performance of SF/β-TCP/PCL scaffolds in promoting long-term cell proliferation, maintaining superior mechanical properties. These findings indicate that the proposed original, simple, and relatively low-cost manufacturing approach enabled the fabrication of scaffolds with excellent mechanical performances, controlled and stable porosity under both dry and physiological-like conditions, and high biocompatibility. The resulting constructs demonstrated promising results for cell proliferation and osteoconductive behavior, supporting their potential suitability as artificial bone substitutes. Full article

(This article belongs to the Special Issue Silk Protein-Based Functional and Innovative Materials for Biomedical Applications)

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17 pages, 5658 KB

Open AccessEditor’s ChoiceArticle

Therapeutic Efficacy of Dual-Targeting Nanoparticles with Low Immunogenicity in the Treatment of Rheumatoid Arthritis

by Renjie Miao, Haoyu Wang, Yitian Jin, Changsheng Liu and Hongyan He

J. Funct. Biomater. 2026, 17(5), 228; https://doi.org/10.3390/jfb17050228 - 6 May 2026

Cited by 1 | Viewed by 1653

Abstract

Rheumatoid arthritis (RA) treatment is severely hindered by the systemic toxicity and limited joint accumulation of conventional therapeutics. To overcome these critical clinical challenges, we engineered a biomimetic dual-targeted nanoplatform (MTX@HSA@M@HA NPs) to precisely deliver methotrexate (MTX) to inflamed synovia. The rationally designed [...] Read more.

Rheumatoid arthritis (RA) treatment is severely hindered by the systemic toxicity and limited joint accumulation of conventional therapeutics. To overcome these critical clinical challenges, we engineered a biomimetic dual-targeted nanoplatform (MTX@HSA@M@HA NPs) to precisely deliver methotrexate (MTX) to inflamed synovia. The rationally designed system encapsulates MTX within human serum albumin (HSA) nanoparticles, which are subsequently cloaked in red blood cell membranes (RBCMs) for robust immune evasion and prolonged systemic circulation. To achieve active targeting, the nanoparticle surface was functionalized with hyaluronic acid (HA) to selectively bind CD44 receptors, which are heavily overexpressed on RA-driving macrophages and fibroblast-like synoviocytes (FLSs). In vitro evaluations demonstrated significantly enhanced cellular internalization by activating RAW264.7 macrophages and FLS, resulting in the potent suppression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) with minimal baseline cytotoxicity. Furthermore, comprehensive in vivo studies using a collagen-induced arthritis (CIA) murine model confirmed that MTX@HSA@M@HA NPs significantly ameliorated joint inflammation, attenuated paw swelling, and rapidly improved functional outcomes compared to free MTX. By synergizing RBCM camouflage with HA-directed active targeting, this nanoplatform maximizes localized therapeutic efficacy while minimizing systemic toxicity, thereby presenting a highly promising and translatable strategy for targeted RA treatment. Full article

(This article belongs to the Section Bone Biomaterials)

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51 pages, 8528 KB

Open AccessEditor’s ChoiceArticle

Biomimetic Deposition of Zn-Doped Calcium Phosphate Coatings on Surface-Activated Ti6Al4V for Multifunctional Implant Interfaces

by Yaimi Martín-Santana, Yadira González-Carranza, Leonel Díaz-Tato, Arturo Juárez-Hernández, Edgar Omar García-Sánchez, Myriam Angélica De La Garza-Ramos, Edén Amaral Rodríguez-Castellanos and Marco Antonio Loudovic Hernández-Rodríguez

J. Funct. Biomater. 2026, 17(5), 225; https://doi.org/10.3390/jfb17050225 - 2 May 2026

Cited by 1 | Viewed by 2188

Abstract

The design of implant surfaces that support bone integration while limiting bacterial colonization remains a central challenge in biomaterials science and engineering. In this work, zinc-doped biomimetic calcium phosphate (CaP-Zn) coatings were fabricated on Ti6Al4V through surface activation followed by deposition in supersaturated [...] Read more.

The design of implant surfaces that support bone integration while limiting bacterial colonization remains a central challenge in biomaterials science and engineering. In this work, zinc-doped biomimetic calcium phosphate (CaP-Zn) coatings were fabricated on Ti6Al4V through surface activation followed by deposition in supersaturated simulated body fluid (SBF). Acid and alkali–calcium treatments produced a porous, calcium-rich interface that enabled the uniform formation of apatite-like CaP layers. Zinc incorporation was achieved without suppressing the formation of CaP phases and led to systematic changes in coating microstructure and surface chemistry. Spectroscopic and structural analyses indicated Zn incorporation within the CaP matrix, consistent with partial Ca²⁺ substitution and its association with poorly crystalline domains. These features promoted controlled ionic release and localized dissolution–reprecipitation behavior. Antibacterial testing against Streptococcus mutans revealed a clear Zn-dependent reduction in bacterial viability, while cytocompatibility remained within acceptable limits at moderate Zn levels. Finally, the coatings combine intrinsic bioactivity with ion-mediated antibacterial functionality, offering a multifunctional surface strategy for advanced titanium-based implants. Full article

(This article belongs to the Special Issue Biomaterials Applied in Dental Sciences)

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17 pages, 3590 KB

Open AccessEditor’s ChoiceArticle

Does Aging Affect PolyJet™ 3D-Printed Teeth for Endodontics? A Micro-CT Evaluation

by Cláudia Barbosa, Tiago Reis, José B. Reis, Margarida Franco, Catarina Batista, Rui B. Ruben, Benjamín Martín-Biedma and José Martín-Cruces

J. Funct. Biomater. 2026, 17(5), 224; https://doi.org/10.3390/jfb17050224 - 2 May 2026

Cited by 1 | Viewed by 1497

Abstract

This study aimed to evaluate the aging effect (6 and 12 months), relative to baseline (0 months), on the dimensional accuracy, morphological stability, and shaping behavior of PolyJet™ 3D-printed teeth (3DPT) produced in two printing orientations (X and Y axes). Specimens (XA0, [...] Read more.

This study aimed to evaluate the aging effect (6 and 12 months), relative to baseline (0 months), on the dimensional accuracy, morphological stability, and shaping behavior of PolyJet™ 3D-printed teeth (3DPT) produced in two printing orientations (X and Y axes). Specimens (XA0, XA6, XA12, YA0, YA6, YA12) were analyzed using microcomputed tomography before and after root canal preparation with the ProTaper Gold^® system. Preoperative analysis included canal volume, centroid, total tooth volume, and total tooth area. Aging-related changes were observed, with significant differences between XA0 and XA12 (p < 0.05), whereas no differences were detected among Y-axis groups (p > 0.05). These findings indicate that X-axis specimens are not comparable over time, while Y-axis specimens maintain baseline consistency. Postoperative evaluation revealed significant differences across aging conditions for most endodontic preparation parameters. Within the limitations of this study, aging had a limited effect on dimensional accuracy but influenced the shaping behavior of 3DPT. Based on these findings, future studies using PolyJet™ 3DPT should report the printing batch and the storage time between fabrication and experimental use, as these factors may influence the comparability and reliability of the results. Full article

(This article belongs to the Special Issue Three-Dimensional Printing and Biomaterials for Medical Applications)

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14 pages, 9703 KB

Open AccessEditor’s ChoiceArticle

Interface-Enhanced Mg/PLA Composite with Superior Mechanical, Biodegradable and Biocompatible Properties for Orthopedic Implants

by Wenchen Teng, Zhuoyi Wang, Ziyue Xu, Jie Xin, Chao Sun, Yi Shao, Cheng Wang, Chenglin Chu, Feng Xue and Jing Bai

J. Funct. Biomater. 2026, 17(5), 210; https://doi.org/10.3390/jfb17050210 - 1 May 2026

Cited by 1 | Viewed by 1050

Abstract

Magnesium (Mg) reinforced polylactic acid (PLA) composites have attracted increasing interest for orthopedic implants to solve the insufficient strength of PLA and to utilize the bioactive advantages of Mg ions in promoting bone formation. However, the weak interfacial adhesion between the Mg and [...] Read more.

Magnesium (Mg) reinforced polylactic acid (PLA) composites have attracted increasing interest for orthopedic implants to solve the insufficient strength of PLA and to utilize the bioactive advantages of Mg ions in promoting bone formation. However, the weak interfacial adhesion between the Mg and PLA limits the applications of the composite. In this study, a dual interfacial enhancement approach was designed to combine surface fluorination with perforation. During hot pressing, molten PLA infiltrates the pores to form a ‘rivet-like’ mechanical interlocking. This structure significantly alters the load transfer and degradation behaviors of the composite. Compared to pure PLA, the dual treatment significantly elevated the bending strength by 49%, alongside an increase in the bending strain from 15% to 25%. Moreover, in vitro degradation tests revealed that this strategy suppresses H₂-induced delamination, and stabilizes both pH and Mg²⁺ release. Consequently, the bending strength remained at 86% after six weeks of in vitro degradation. In addition, the composite exhibits excellent biocompatibility, with MC3T3-E1 cell viability exceeding 90% in 100% extract. These results demonstrate that the reinforced Mg/PLA composite exhibits excellent mechanical properties, degradation stability, and biocompatibility, showing high potential for load-bearing orthopedic fixation applications. Full article

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

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18 pages, 899 KB

Open AccessEditor’s ChoiceSystematic Review

Biogenic Selenium Nanoparticles Functionalized with Natural Polymers or Phytochemicals for Targeted Disruption of Candida spp. Biofilms on Denture Materials: A Systematic Review

by Zofia Stefanik, Paweł Ścierski, Maciej Dobrzyński, Natalia Stefanik, Magdalena Antonowicz-Hüpsch and Rafał Wiench

J. Funct. Biomater. 2026, 17(5), 216; https://doi.org/10.3390/jfb17050216 - 1 May 2026

Viewed by 1548

Abstract

Background: Denture stomatitis is strongly associated with Candida biofilms on prosthetic surfaces and remains difficult to manage due to biofilm persistence and antifungal resistance. Selenium-based nanomaterials, particularly biogenic selenium nanoparticles (SeNPs) functionalized with natural polymers or phytochemicals, have emerged as potential material-centered strategies [...] Read more.

Background: Denture stomatitis is strongly associated with Candida biofilms on prosthetic surfaces and remains difficult to manage due to biofilm persistence and antifungal resistance. Selenium-based nanomaterials, particularly biogenic selenium nanoparticles (SeNPs) functionalized with natural polymers or phytochemicals, have emerged as potential material-centered strategies for biofilm control. Objective: To systematically evaluate the antifungal and antibiofilm effects of selenium-based nanomaterials on Candida biofilms in the context of denture materials. Methods: A systematic review was conducted in accordance with the PRISMA guidelines and registered in PROSPERO. Multiple databases were searched from inception without language restrictions. Eligible studies included experimental investigations of biogenic or functionalized SeNPs or organoselenium compounds targeting Candida biofilms on denture materials or in relevant in vitro models. A qualitative synthesis was performed due to anticipated heterogeneity. Results: Eleven studies met the inclusion criteria. Of these, four studies directly evaluated selenium-based interventions on denture materials, while seven provided supporting mechanistic evidence using in vitro models on non-denture substrates. Across denture-related studies, selenium-based modifications reduced fungal adhesion, biofilm biomass, and colony-forming units, without detrimental effects on material properties. Functionalization with polymers or phytochemicals was associated with enhanced antifungal activity and nanoparticle stability. Mechanistic studies suggested multimodal antifungal effects, including membrane disruption, inhibition of virulence factors, and modulation of biofilm-related pathways. Methodological quality was moderate, with common limitations in reporting and experimental standardization. Conclusions: Functionalized biogenic SeNPs show promising antifungal and antibiofilm activity against Candida in preclinical denture-related models. However, all available evidence is in vitro, with no in vivo or clinical studies identified. Substantial heterogeneity and limited long-term safety data preclude clinical recommendations. Further research should focus on standardized methodologies, clinically relevant in vivo models, and controlled clinical trials to assess translational potential. Full article

(This article belongs to the Section Dental Biomaterials)

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64 pages, 9900 KB

Open AccessEditor’s ChoiceReview

Biomaterials’ Role in Improving Patient Care from Drug Testing and Delivery to Theragnostics and Regenerative Medicine

by Sabina Cristiana Badulescu, Emma Adriana Ozon, Adina Magdalena Musuc, Manuela Diana Ene and Rica Boscencu

J. Funct. Biomater. 2026, 17(5), 214; https://doi.org/10.3390/jfb17050214 - 1 May 2026

Viewed by 1470

Abstract

Over the past 200 years (1820–2020), global life expectancy has nearly tripled, increasing from 26 to 72.91 years, due to factors such as poverty reduction and public health initiatives. Today, society faces different challenges than it did centuries ago. In patient care and [...] Read more.

Over the past 200 years (1820–2020), global life expectancy has nearly tripled, increasing from 26 to 72.91 years, due to factors such as poverty reduction and public health initiatives. Today, society faces different challenges than it did centuries ago. In patient care and healthcare system priorities, the goal is to develop smart, feasible, long-lasting, cost-effective, readily available, adverse-reaction-free, adaptable, and personalized solutions that minimize patient discomfort, reduce caregiver effort, and decrease hospitalization duration and costs. In this context, biomaterials serve as versatile tools capable of performing a wide range of diagnostic, therapeutic, and theragnostic functions. Thanks to their biocompatibility, biodegradability, surface chemistry, and responsiveness, biomaterials are currently addressing issues such as patient compliance (through controlled drug-delivery systems and smart wound dressings), long transplant waiting lists, transplant rejection, non-adaptable prosthetics (artificial organs), oncology treatment efficacy (nano-formulations for theragnostics and multiple tumor targeting), and inconsistent in vitro drug-testing models (organs-on-a-chip). In this review, we focus on biomaterials’ smartness, then explore databases for efficient product design, and finally highlight their applications in the biomedical field, especially in drug delivery, tissue engineering, and regenerative medicine. Full article

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

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29 pages, 2781 KB

Open AccessEditor’s ChoiceReview

Tumor-Targeted Delivery Therapy Based on PLGA Nanoparticles

by Fang Wu, Yuan Gao, Yongjie Chi, Danyang Wang, Siqi Zhang, Ocean Cheung, Kai Zhao, Hongsheng Lu, Qi Chen, Yu Chen, Lianyan Wang and Yanhua Zhu

J. Funct. Biomater. 2026, 17(5), 207; https://doi.org/10.3390/jfb17050207 - 22 Apr 2026

Viewed by 3902

Abstract

Poly(lactic acid-lactic acid) (PLGA) has demonstrated significant application potential in tumor-targeted drug delivery systems due to its excellent biocompatibility, degradability, and multifunctionality for loading various therapeutic agents. PLGA nanoparticles (NPs) can achieve targeted delivery to tumor cells through specific surface modifications and stimulus-responsive [...] Read more.

Poly(lactic acid-lactic acid) (PLGA) has demonstrated significant application potential in tumor-targeted drug delivery systems due to its excellent biocompatibility, degradability, and multifunctionality for loading various therapeutic agents. PLGA nanoparticles (NPs) can achieve targeted delivery to tumor cells through specific surface modifications and stimulus-responsive release mechanisms, significantly enhancing drug accumulation efficiency at tumor sites while reducing toxic side effects on normal tissues. This review systematically summarizes the fundamental physicochemical properties of PLGA materials and recent advances in tumor-targeting strategies for PLGA NPs. It comprehensively elucidates research breakthroughs in PLGA-based delivery systems regarding stimulus-response mechanisms, passive targeting, active targeting, and tumor combination immunotherapy, while revealing the intrinsic logic of synergistic strategies for enhancing targeting efficiency. Finally, from the perspective of clinical translation and individualized oncology, this review conducts an in-depth assessment of the current challenges and looks forward to future research directions, aiming to provide forward-looking guidance for the development of precision nanomedicine. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Drug Delivery (2nd Edition))

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21 pages, 5460 KB

Open AccessEditor’s ChoiceArticle

ZrO₂ Ceramic without and with Fullerene C₆₀ Films: In Vitro Direct-Contact Model Using E. coli and S. aureus Bacteria

by Annett Dorner-Reisel, Jialin Li, Marta Trzaskowska, Vladyslav Vivcharenko, Jiacheng Chu, Emma Freiberger, Uwe Ritter, Agata Przekora, Aneta Zima, Tao Wang and Jens Moje

J. Funct. Biomater. 2026, 17(4), 206; https://doi.org/10.3390/jfb17040206 - 21 Apr 2026

Viewed by 3228

Abstract

Zirconia is known as a strong and bioinert load-bearing material for dental implants. It typically exhibits no antibacterial activity. Inflammation is a crucial problem for dental implant surgery: about 3–5% of all dental implants experience inflammation. This study demonstrates that either fullerene C [...] Read more.

Zirconia is known as a strong and bioinert load-bearing material for dental implants. It typically exhibits no antibacterial activity. Inflammation is a crucial problem for dental implant surgery: about 3–5% of all dental implants experience inflammation. This study demonstrates that either fullerene C₆₀ films or a tribomechanical loading of zirconia without the fullerene C₆₀ coating can cause an improvement in antibacterial activity against Gram-positive Staphylococcus aureus. This moderate antibacterial activity is especially important, because a strong antibacterial effect could disturb the sensitive and beneficial oral bacterial biota. In the present study, different fullerene C₆₀ films were examined. In addition to fullerene C₆₀ film in an “as deposited” condition, treatment with nitrogen plasma as well as tribomechanical produced surface patterns with and without plasma post-treatment were tested. An 85.8% (log reduction 0.85) reduction in Gram-positive Staphylococcus aureus bacterial formation was observed on the zirconia with fullerene C₆₀ film. Plasma treatment of the C₆₀ film increases the antibacterial impact to 72.2% (log reduction 0.56) in comparison to zirconia without fullerene C₆₀ film. Also, tribomechanical loaded fullerene C₆₀ films suppress the growth of Gram-positive Staphylococcus aureus. The tribomechanical loading seems to compensate for the effect of the plasma treatment. ZrO₂ samples with fullerene C₆₀ film and tribomechanical loading achieve an increase in antibacterial impact of 83.36% (log reduction 0.78). Furthermore, surprisingly yttria-stabilized zirconia bioceramic without fullerene C₆₀ film also shows an improved antibacterial efficacy after a tribomechanical patterning procedure. The addition of surface patterning on the ZrO₂ by scratching microgroove arrangements with a diamond tip, increased the antibacterial effect against Gram-positive Staphylococcus aureus by 70.46% (log reduction 0.53). Full article

(This article belongs to the Special Issue Antibacterial Biomaterials for Medical Applications)

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24 pages, 5670 KB

Open AccessEditor’s ChoiceReview

4D Printing in Biomedical Implants and Functional Healthcare Devices

by Muhammad Shafiq and Liaqat Zeb

J. Funct. Biomater. 2026, 17(4), 203; https://doi.org/10.3390/jfb17040203 - 20 Apr 2026

Cited by 2 | Viewed by 2897

Abstract

Four-dimensional (4D) printing integrates additive manufacturing with stimuli-responsive materials to fabricate biomedical implants and functional healthcare devices that undergo programmed, time-dependent changes in shape or function. Unlike static 3D-printed constructs, 4D-printed systems can respond to clinically relevant stimuli such as temperature, hydration, pH, [...] Read more.

Four-dimensional (4D) printing integrates additive manufacturing with stimuli-responsive materials to fabricate biomedical implants and functional healthcare devices that undergo programmed, time-dependent changes in shape or function. Unlike static 3D-printed constructs, 4D-printed systems can respond to clinically relevant stimuli such as temperature, hydration, pH, light (including near-infrared), magnetic fields, or electrical inputs. These triggers drive defined actuation mechanisms, most commonly thermomechanical shape-memory recovery, swelling-induced morphing, and magnetothermal activation. This review synthesizes the principal material platforms used for biomedical 4D printing, including shape-memory polymers and alloys, hydrogels, liquid-crystal elastomers, and responsive composites, and links material choice to device behavior and translational feasibility. Applications are discussed across self-expanding stents, cardiac occluders, tissue-engineered constructs, implantable drug delivery systems, and adaptive wearables. Key translational challenges include sterilization compatibility, manufacturing reproducibility and quality control, safe stimulus delivery, predictable biodegradation and long-term biocompatibility, and regulatory pathway definition. Full article

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

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14 pages, 14338 KB

Open AccessEditor’s ChoiceArticle

Recombinant Human SLPI Surface Functionalization Enhances Early Osseointegration and Biomechanical Stability of Titanium Implants in Rat Model

by Wannapat Chouyratchakarn, Burin Boonsri, Surasak Tangkamonsri, Watchara Thepsupa, Chayarop Supanchart and Sarawut Kumphune

J. Funct. Biomater. 2026, 17(4), 205; https://doi.org/10.3390/jfb17040205 - 20 Apr 2026

Cited by 1 | Viewed by 2305

Abstract

Titanium and its alloys are used in dental and orthopedic implants. However, long-term stability remains a clinical challenge. To overcome this limitation, surface modification has been investigated to improve surface properties. Our previous study demonstrated that the immobilization of secretory leukocyte protease inhibitor [...] Read more.

Titanium and its alloys are used in dental and orthopedic implants. However, long-term stability remains a clinical challenge. To overcome this limitation, surface modification has been investigated to improve surface properties. Our previous study demonstrated that the immobilization of secretory leukocyte protease inhibitor (SLPI) on the titanium surface promotes osteoblast adhesion, proliferation, and differentiation in vitro. The current study demonstrated the first in vivo evaluation of SLPI as a bioactive coating for medical implants. Grade 5 titanium screws were coated with 10 µg/mL of recombinant human SLPI (rhSLPI) for 24 h via simple physical adsorption, and the results were preliminarily validated via FE-SEM and ELISA. These SLPI-coated titanium screws (TiSs) were then placed in the tibia of Sprague–Dawley rats for 4 and 8 weeks. The hematological and biochemical parameters (BUN, Creatinine, AST, and Troponin I) demonstrated no acute systemic alterations within the 8-week period across all groups. Moreover, micro-computed tomography (micro-CT) and histological analysis revealed significantly higher bone volume fraction (%BV/TV) at 4 weeks compared to uncoated controls (20.64% ± 2.452% vs. 11.73% ± 0.524%). Finally, the biomechanical stability of implants, assessed using the removal torque test, showed that TiSs showed higher strength compared to Ti at both 4 and 8 weeks. In conclusion, this study represents a novel approach to transitioning rhSLPI-coated titanium evaluation from in vitro models to an in vivo rat model. rhSLPI surface functionalization enhances early-stage osseointegration and improves implant mechanical stability without acute hematological and biochemical alterations. These proof-of-concept findings suggest the potential of SLPI as a bioactive coating strategy. Full article

(This article belongs to the Section Bone Biomaterials)

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23 pages, 3916 KB

Open AccessEditor’s ChoiceArticle

How Bioactive Glass S53P4 Kills Bacteria

by Deeksha Rajkumar, Adrian Stiller, Jurian Wijnheijmer, Ireen M. Schimmel, Leendert W. Hamoen, Leena Hupa, Nicole N. van der Wel, Payal P. S. Balraadjsing and Sebastian A. J. Zaat

J. Funct. Biomater. 2026, 17(4), 201; https://doi.org/10.3390/jfb17040201 - 19 Apr 2026

Cited by 1 | Viewed by 2553

Abstract

Bioactive glass (BAG) S53P4 is a clinically approved bone substitute with antibacterial, osteoconductive and osteostimulatory properties. Its antibacterial effect is associated with ion release, local pH elevation and osmolality, but the precise biochemical and biophysical mode-of-action is unclear. This study investigates the antibacterial [...] Read more.

Bioactive glass (BAG) S53P4 is a clinically approved bone substitute with antibacterial, osteoconductive and osteostimulatory properties. Its antibacterial effect is associated with ion release, local pH elevation and osmolality, but the precise biochemical and biophysical mode-of-action is unclear. This study investigates the antibacterial mechanism of BAG S53P4 eluates. BAG eluates, collected at 2, 4, 8, and 24 h, eradicated Staphylococcus aureus. Elemental analysis revealed an early increase in concentrations of Si and Na, a later rise in Ca, depletion of P over time and rapid loss of Mg. Membrane disturbances occurred within 5 min, evident by permeability for SYTOX, aligning with time-kill kinetics for S. aureus and Bacillus subtilis. In B. subtilis, 2h-BAG-eluate induced rapid delocalization of marker proteins for cell division and DNA repair, signaling membrane potential collapse and nucleoid condensation. Transcriptomics revealed early transcription remodeling reflecting ionic and energetic imbalance, including disruption of central metabolism, redox homeostasis, and translational stability. Scanning electron microscopy revealed severe cell surface damage and particulate deposits on S. aureus. Transmission electron microscopy showed cell envelop disruptions and cytoplasmic leakage. Energy dispersive X-ray analysis identified Si on bacterial cell surface at 4 h and intracellular accumulation in punctured, empty cells at 24 h. Overall, BAG ionic dissolution products kill bacteria through a stepwise mechanism involving membrane damage, protein delocalization and metabolic impairment, accompanied by Si deposition on bacterial surfaces and loss of Mg. This finally leads to cell wall degradation, cytoplasmic content leakage and further Si deposition on the cells and inside cell ghosts. Full article

(This article belongs to the Special Issue Antibacterial Biomaterials for Medical Applications)

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16 pages, 16204 KB

Open AccessEditor’s ChoiceArticle

ATP-Responsive Bimetallic Metal–Organic Frameworks Amplify Oxidative Stress in the Tumor Microenvironment for Synergistic Chemo-Immunotherapy

by You Li, Wenxin Zhang, Zitao Xu, Shixin Ma, Yufei Xiong, Li Yu, Huiling Gao, Yang Shu and Teng Fei

J. Funct. Biomater. 2026, 17(4), 199; https://doi.org/10.3390/jfb17040199 - 19 Apr 2026

Viewed by 2068

Abstract

Metal ion-based chemo-immunotherapy is often limited by rigid intracellular metal homeostasis, insufficient reactive oxygen species (ROS) accumulation, and an immunosuppressive tumor microenvironment (TME). To overcome these limitations, we engineered an ATP-responsive, core–shell bimetallic nanoreactor (Cu/ZIF@PDA, termed CZP) featuring a precisely controlled ~25 nm [...] Read more.

Metal ion-based chemo-immunotherapy is often limited by rigid intracellular metal homeostasis, insufficient reactive oxygen species (ROS) accumulation, and an immunosuppressive tumor microenvironment (TME). To overcome these limitations, we engineered an ATP-responsive, core–shell bimetallic nanoreactor (Cu/ZIF@PDA, termed CZP) featuring a precisely controlled ~25 nm biomimetic polydopamine (PDA) coating. Triggered by elevated tumoral ATP levels, CZP undergoes coordination-induced disassembly and promotes oxidative stress amplification. Specifically, the PDA shell acts as a superoxide dismutase (SOD) mimetic to continuously supply H₂O₂, fueling Cu²⁺-mediated Fenton-like reactions to unleash highly toxic hydroxyl radicals (•OH) while aggressively depleting the intracellular glutathione (GSH) pool. This irreversible oxidative damage, coupled with Zn²⁺-induced mitochondrial dysfunction, triggers profound mitochondrial DNA (mtDNA) leakage. Crucially, this cytosolic DNA robustly activates the cGAS-STING signaling axis, driving a massive surge in immunogenic cell death (ICD) and significantly promoting dendritic cell (DC) maturation. Furthermore, CZP markedly inhibited primary tumor growth in vivo and showed protection in a tumor re-challenge model, accompanied by enhanced dendritic cell maturation. These findings support the potential of this ATP-responsive bimetallic nanoplatform to promote antitumor immune activation. Full article

(This article belongs to the Section Biomaterials for Cancer Therapies)

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13 pages, 2720 KB

Open AccessEditor’s ChoiceArticle

Bone Compatibility of Experimental Ti–Ag and Ti–Cu Alloy Dental Implants in a Beagle Dog Model

by Yasumitsu Ohtsuka, Taichi Tenkumo, Masatoshi Takahashi, Yasuhiro Nakanishi, Hiroaki Takebe and Takashi Nezu

J. Funct. Biomater. 2026, 17(4), 198; https://doi.org/10.3390/jfb17040198 - 18 Apr 2026

Viewed by 1851

Abstract

Titanium–silver (Ti–Ag) and titanium–copper (Ti–Cu) alloys have been developed to improve the mechanical properties and machinability of titanium (Ti) for dental applications while maintaining corrosion resistance comparable to that of pure Ti. Herein, cylindrical dental implants composed of experimental Ti–20Ag, Ti–30Ag, Ti–5Cu, and [...] Read more.

Titanium–silver (Ti–Ag) and titanium–copper (Ti–Cu) alloys have been developed to improve the mechanical properties and machinability of titanium (Ti) for dental applications while maintaining corrosion resistance comparable to that of pure Ti. Herein, cylindrical dental implants composed of experimental Ti–20Ag, Ti–30Ag, Ti–5Cu, and Ti–10Cu (mass%) alloys were fabricated and implanted into the jawbones of beagle dogs to evaluate bone compatibility. Pure Ti and Ti–6Al–4V alloy implants were used as controls. Because the implant surfaces were mechanically polished, the experimental alloys, which exhibited higher hardness than Ti, showed lower surface roughness than Ti. Radiographic observations revealed no remarkable bone resorption around any implants during the experimental period. Histological evaluation demonstrated new bone formation and partial bone contact around implants at 1 and 3 months post-implantation. Although the bone–implant contact ratio was relatively low owing to the cylindrical implant design and limited initial stability, no significant differences were observed between the experimental alloys and Ti. These results indicate that Ti–Ag and Ti–Cu alloys improve mechanical properties while maintaining bone compatibility comparable to that of Ti, suggesting their potential as candidate materials for dental implant applications, particularly for narrow dental implants. Full article

(This article belongs to the Special Issue Functional Dental Materials for Orthodontics and Implants)

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20 pages, 2967 KB

Open AccessEditor’s ChoiceArticle

Using Citric-Acid-Based Anodization to Form Magnesium-Doped Carbonated Apatite-Containing Oxides on Solid and 3D-Printed Titanium Substrates

by Amisha Parekh, Arunendu Ettuthaiyil Sambasivan, Mikyle Paul, Arash Soltani, Aya Ali, John Tucker, Jonathan W. Pegues, Nima Shamsaei, Amol V. Janorkar and Michael D. Roach

J. Funct. Biomater. 2026, 17(4), 190; https://doi.org/10.3390/jfb17040190 - 14 Apr 2026

Viewed by 929

Abstract

With increasing life expectancy and an aging global population, the demand for orthopedic and dental implants is increasing. Recently developed, citric-acid-based anodization processes facilitate the production of more bioactive oxide layers by incorporating important bone minerals such as Ca, P, and Mg and [...] Read more.

With increasing life expectancy and an aging global population, the demand for orthopedic and dental implants is increasing. Recently developed, citric-acid-based anodization processes facilitate the production of more bioactive oxide layers by incorporating important bone minerals such as Ca, P, and Mg and forming bone-like crystalline compounds such as carbonated apatite on titanium implant materials. The primary goal of the present study was to evaluate the applicability of these anodization processes to solid and 3D-printed titanium alloy substrates. The anodized oxides produced on each solid or 3D-printed lattice substrate revealed multi-scaled surface roughness profiles as evidenced by scanning electron microscopy, optical microscopy, and surface roughness analyses. Additionally, each oxide group was shown to incorporate substantial amounts of Ca, P, and Mg bone-mineral dopants and form AB-type carbonated apatite, as shown using a combination of energy-dispersive spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and attenuated total reflectance–Fourier transform infrared spectroscopy analyses. Finally, each oxide group showed sustained Ca, P, and Mg ion release during an inductively coupled plasma spectroscopy dissolution assessment, and demonstrated early apatite-forming ability during simulated body fluid bioactivity testing. The findings of this study show much promise for the applicability of these novel oxide coatings to a wide variety of future titanium implant applications. Full article

(This article belongs to the Special Issue Drug- and Ion-Releasing Implants)

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20 pages, 11367 KB

Open AccessEditor’s ChoiceArticle

Design and Development of Teixobactin Analog-Loaded Magnetic Nanocomposites for Biofilm Destruction and Pathogen Elimination

by Huaxiang Lei, Ye Liang, Xuechen Li, Xiaojing Huang, Chengfei Zhang and Ting Zou

J. Funct. Biomater. 2026, 17(4), 189; https://doi.org/10.3390/jfb17040189 - 13 Apr 2026

Viewed by 569

Abstract

Although teixobactin, a promising cyclic undecadepsipeptide, exhibits efficacy against Gram-positive bacteria due to its novel mode of action and low potential for resistance, its clinical application is limited by two key shortcomings: ineffectiveness against Gram-negative bacteria and poor penetration of the protective extracellular [...] Read more.

Although teixobactin, a promising cyclic undecadepsipeptide, exhibits efficacy against Gram-positive bacteria due to its novel mode of action and low potential for resistance, its clinical application is limited by two key shortcomings: ineffectiveness against Gram-negative bacteria and poor penetration of the protective extracellular polymeric substance (EPS) in biofilms. This renders it unsuitable for targeting the polymicrobial biofilms, which are the cause of periodontitis and peri-implantitis. We designed a modified teixobactin analog by integrating rhamnolipid, Ag@Fe₃O₄ nanoparticles, and _L-Chg₁₀-teixobactin to obtain a novel magnetic nanoparticle (MNP). The MNP demonstrates the ability to simultaneously degrade EPS, penetrate biofilm structures, and eliminate both G⁺ and G⁻ pathogens under a rotating magnetic field (RMF). Rhamnolipid grafting degraded 52.5% of biofilm EPS. MNPs showed broad-spectrum antimicrobial activity, with minimal inhibitory concentrations from 100 to 200 µg/mL. Combined with RMF, biofilm eradication rates reached 97.0% (E. faecalis), 97.7% (S. gordonii), 88.4% (P. gingivalis), and 74.2% (F. nucleatum). The biofilm thickness was reduced from 19.4 ± 2.9 µm to 7.4 ± 1.0 µm, and the biofilm biomass was reduced by 68.5%. This combined strategy integrates enzymatic EPS degradation, magneto-mechanical disruption, and dual antimicrobial action, offering a promising topical therapy for periodontitis and peri-implantitis. Full article

(This article belongs to the Section Antibacterial Biomaterials)

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24 pages, 4530 KB

Open AccessEditor’s ChoiceArticle

Granulate-to-Filament: An Extrusion-Mixed PLA–Human Bone Material System for 3D-Printed Bone Scaffolds

by Jonas Neijhoft, Hela Weslati, Volker Eras, Jan Brune, Maximilian Leiblein, Santiago Bianconi, Nicolas Söhling, Lewin Busse, René Verboket, Johannes Frank, Ingo Marzi and Dirk Henrich

J. Funct. Biomater. 2026, 17(4), 187; https://doi.org/10.3390/jfb17040187 - 11 Apr 2026

Viewed by 1104

Abstract

Fused filament fabrication (FFF) enables patient-specific scaffolds for critical-size bone defects, but most filaments are bioinert and difficult to functionalize at high particulate loadings due to segregation, agglomeration, clogging, and diameter instability. We developed a mechanism-guided extrusion toolkit to stabilize polylactic acid (PLA) [...] Read more.

Fused filament fabrication (FFF) enables patient-specific scaffolds for critical-size bone defects, but most filaments are bioinert and difficult to functionalize at high particulate loadings due to segregation, agglomeration, clogging, and diameter instability. We developed a mechanism-guided extrusion toolkit to stabilize polylactic acid (PLA) filaments containing human demineralized bone matrix (DBM) or cortical granulate (CG) up to 70 wt%. PLA was ground, dried, silicone pre-coated, and compounded with DBM or CG (25/40/70 wt%) using starve-fed extrusion, sequential extrusion, and post-die mixing to maintain stable diameters. FFF produced disks and tubes. MSC adhesion was assessed by SEM. qPCR (control vs. osteogenic medium) quantified RUNX2, ALP, BGLAP, COL1A, VEGF, IL-6, MAPK8. Tubes underwent three-point bending. The toolkit yielded printable, dimensionally stable filaments at 25–70 wt% with uniform dispersion and surface-exposed filler. Both composites increased early mesenchymal stromal cells (MSC) adhesion versus PLA. RUNX2 was increased on DBM40 versus PLA. VEGF was elevated on CG25 (DBM40 trend). Under osteogenic medium, IL-6 and MAPK8 were generally reduced. Mechanics were loading-dependent: CG25 exceeded CG70 and DBM25, while DBM40/70 recovered stiffness versus DBM25. A mechanism-guided extrusion toolkit enables high-loading PLA–DBM/CG filaments with excellent printability and material-specific biological and mechanical advantages over PLA. Full article

(This article belongs to the Special Issue Translational Biomedical Devices and Biomaterials: Bridging Biology, Engineering and Medicine)

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41 pages, 3003 KB

Open AccessEditor’s ChoiceReview

Advances and Challenges in Tissue Engineering: Biomaterials, Cellular Strategies, and Clinical Applications

by Rosana Farjaminejad, Samira Farjaminejad, Franklin Garcia-Godoy, Anand Marya, Ludovica Nucci and Abdolreza Jamilian

J. Funct. Biomater. 2026, 17(4), 184; https://doi.org/10.3390/jfb17040184 - 10 Apr 2026

Cited by 2 | Viewed by 2256

Abstract

Tissue engineering integrates concepts from medicine, biology, and engineering to create living constructs capable of repairing, replacing, or supporting damaged tissues. This multidisciplinary field relies on the interplay between biomaterials, cellular sources, and bioactive signaling to achieve functional tissue regeneration. This review provides [...] Read more.

Tissue engineering integrates concepts from medicine, biology, and engineering to create living constructs capable of repairing, replacing, or supporting damaged tissues. This multidisciplinary field relies on the interplay between biomaterials, cellular sources, and bioactive signaling to achieve functional tissue regeneration. This review provides a comprehensive overview of recent advances in scaffold design, highlighting natural, synthetic, and hybrid materials, as well as innovative fabrication techniques such as electrospinning, 3D bioprinting, and smart biomaterials. It discusses the role of stem cells and growth factors in directing regeneration and examines a wide range of clinical applications, including skin regeneration, cartilage repair, bone tissue engineering, dental and periodontal regeneration, nerve repair, cardiac tissue engineering, liver tissue models, and ophthalmic applications. Current challenges, such as immune responses, limited vascularization, scalability, and regulatory barriers, are addressed alongside emerging strategies aimed at improving clinical translation. By integrating diverse tissue types and engineering approaches within a unified framework, this review offers a broad yet detailed perspective on the current state and future directions of regenerative medicine. Full article

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

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20 pages, 4154 KB

Open AccessEditor’s ChoiceArticle

Potentiation of a Porous Silicon Therapeutic Vaccine in Colorectal Cancer via Oxaliplatin-Mediated Regulation of Myeloid-Driven Immunosuppression

by Yongbin Liu, Busra Akay Hacan, Junjun Zheng, Xueying Ge, Dongfang Yu, Zhe Chen, Yitian Xu, Ning Shao, Haifa Shen, Xuewu Liu, Roderic I. Pettigrew, Ping-Ying Pan, Shu-Hsia Chen and Junhua Mai

J. Funct. Biomater. 2026, 17(4), 185; https://doi.org/10.3390/jfb17040185 - 10 Apr 2026

Cited by 1 | Viewed by 1224

Abstract

Although immunotherapy has shown great promise in treating various types of cancer, advanced tumors are often refractory due to a highly immunosuppressive tumor microenvironment (TME). We previously engineered a cancer therapeutic vaccine platform, µGCVax, by co-loading tumor antigen peptides, STING and TLR9 agonists [...] Read more.

Although immunotherapy has shown great promise in treating various types of cancer, advanced tumors are often refractory due to a highly immunosuppressive tumor microenvironment (TME). We previously engineered a cancer therapeutic vaccine platform, µGCVax, by co-loading tumor antigen peptides, STING and TLR9 agonists into porous silicon microparticles. While effective in models with lower disease burden, its efficacy against advanced colorectal cancer (CRC) was less promising due to the accumulation of myeloid-derived suppressor cells (MDSCs) in TMEs. In this study, we investigated whether µGCVax-based immunotherapy in advanced CRCs could be potentiated via regulating MDSCs to reprogram the TME. In an advanced CT26 murine CRC model, we assessed µGCVax in combination with oxaliplatin, a standard CRC chemotherapeutic with established immunomodulatory effects. We demonstrated that oxaliplatin was preferentially taken up by monocytic MDSCs (M-MDSCs) and effectively reduced their abundance in the bone marrow, blood, spleen, and tumor. Relief of this immunosuppressive TME increased intratumoral infiltration of antigen-specific CD8⁺ T cells. Ultimately, the combination of oxaliplatin with µGCVax induced robust regression of established CRC tumors. These findings highlight that oxaliplatin synergizes with µGCVax by overcoming MDSC-mediated immunosuppression and enhancing antitumor immunity, representing a promising chemo-immunotherapy strategy for advanced CRC. Full article

(This article belongs to the Special Issue Functional Porous Materials for Biomedical Applications)

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17 pages, 3087 KB

Open AccessEditor’s ChoiceArticle

Bone Regeneration After Maxillary Sinus Augmentation with Allogeneic and Xenogeneic Biomaterials with Adjunctive Photobiomodulation: Histological and Radiological Secondary Outcomes of a Randomized Clinical Trial

by Sebastian Dominiak, Aleksandra Piotrowska, Marzena Dominiak, Tomasz Gedrange, Piotr Dzięgiel, Alicja Baranowska, Michał Ciszyński, Jakub Hadzik and Paweł Kubasiewicz-Ross

J. Funct. Biomater. 2026, 17(4), 186; https://doi.org/10.3390/jfb17040186 - 10 Apr 2026

Cited by 3 | Viewed by 1436

Abstract

Background: Atrophy of the alveolar ridge in the posterior maxilla often requires sinus floor elevation prior to implant placement. Photobiomodulation using low-level laser therapy (LLLT) has been suggested as a supportive approach for bone healing, although data based on histological evaluation are still [...] Read more.

Background: Atrophy of the alveolar ridge in the posterior maxilla often requires sinus floor elevation prior to implant placement. Photobiomodulation using low-level laser therapy (LLLT) has been suggested as a supportive approach for bone healing, although data based on histological evaluation are still limited. Methods: This study presents histological and radiological secondary outcomes of a randomized clinical trial on bone regeneration after lateral window sinus augmentation. Twenty patients were allocated according to grafting material (allogeneic or xenogeneic) and the use of adjunctive LLLT. After 6 months, bone core biopsies were obtained at the time of implant placement and processed for histological analysis. Radiological bone gain was assessed using CBCT. Results: Bone gain was achieved in all groups, allowing implant placement in every case. Mean bone gain reached 7.53 ± 3.32 mm in LLLT-treated sites and 7.02 ± 2.00 mm in controls, with no statistically significant differences. Histological analysis confirmed trabecular bone formation across all groups. Mild inflammatory cell infiltrates were observed more frequently in LLLT-treated sites (p = 0.029), although this finding was not associated with impaired tissue organization or compromised healing. Conclusions: Both allogeneic and xenogeneic grafts showed good biocompatibility and supported effective bone regeneration after sinus augmentation. The addition of photobiomodulation did not demonstrate statistically significant clinical or radiological benefits within this exploratory cohort, but it may be associated with subtle differences in tissue remodeling. Full article

(This article belongs to the Special Issue New Biomaterials in Periodontology and Implantology)

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27 pages, 8951 KB

Open AccessEditor’s ChoiceArticle

Comparative Late Effects of Hemostatic Biomaterials on Wound Healing at 14 and 30 Days: An In Vivo Animal Study

by Polina Shabes, Julian-Dario Rembe, Arzu Mammadova, Katharina Henrika Beckamp, Markus Udo Wagenhäuser, Wiebke Ibing, Hubert Schelzig and Waseem Garabet

J. Funct. Biomater. 2026, 17(4), 183; https://doi.org/10.3390/jfb17040183 - 9 Apr 2026

Viewed by 1103

Abstract

Hemostatic biomaterial agents are widely used during surgery and trauma care to control bleeding, yet their effects on wound healing remain incompletely understood. This study evaluated the impact of oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a gelatin-based hemostat (GELA) on [...] Read more.

Hemostatic biomaterial agents are widely used during surgery and trauma care to control bleeding, yet their effects on wound healing remain incompletely understood. This study evaluated the impact of oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a gelatin-based hemostat (GELA) on wound healing at 14 and 30 days in a mouse model. Full-thickness wounds were created in C57BL/6J mice (n = 192) and compared to sham controls. Tissue samples were analyzed histologically, supported by immunohistochemistry for Ki-67 and α-SMA and qPCR for VEGF, TGF-β, and FGF-2. Histology demonstrated preserved tissue architecture across groups with progressive resorption of cellulose-based materials, whereas GELA showed localized fibrous structures and enhanced extracellular matrix formation. At day 14, no significant differences were observed in proliferation, contraction, VEGF, or FGF-2 expression; however, TGF-β was significantly reduced in the ORC group. By day 30, GELA significantly increased epidermal proliferation, while contraction markers were elevated in both GELA and ORC. VEGF expression was reduced in GELA and ORC, whereas ONRC showed increased TGF-β expression. FGF-2 remained unchanged across groups. All investigated hemostatic materials were well tolerated during the early postoperative phase (up to day 14), indicating short-term biocompatibility within the scope of this model. In contrast, material-specific differences in cellular activity and growth factor expression became apparent during the later remodeling phase (day 30). These findings suggest differential effects on cellular and molecular aspects of tissue remodeling; however, no conclusions can be drawn regarding overall healing quality or clinical safety, as no quantitative macroscopic or functional outcome measures were assessed. Full article

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

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17 pages, 14168 KB

Open AccessEditor’s ChoiceArticle

Structure and Mechanical Properties of Ti-38Zr-(8-10)Nb (at. %) Alloys for Medical Use

by Konstantin V. Sergienko, Sergei V. Konushkin, Yaroslava A. Morozova, Maria A. Sudarchikova, Mikhail A. Kaplan, Vadim K. Zhidkov, Tatyana M. Sevostyanova, Aleksander V. Simakin, Ilya V. Baimler, Mikhail A. Sevostyanov and Alexey G. Kolmakov

J. Funct. Biomater. 2026, 17(4), 179; https://doi.org/10.3390/jfb17040179 - 3 Apr 2026

Cited by 1 | Viewed by 669

Abstract

The research described in this article is a continuation of a series of studies on biocompatible materials, focused on finding the optimal alloy composition and heat treatment regimes. The use of materials with a low Young’s modulus ensures the long-term safety of the [...] Read more.

The research described in this article is a continuation of a series of studies on biocompatible materials, focused on finding the optimal alloy composition and heat treatment regimes. The use of materials with a low Young’s modulus ensures the long-term safety of the implant by reducing the stress shielding effect, which causes bone resorption. This work investigates the effect of alloying with niobium in the range of (8–10) at. % on the Ti-38Zr alloy, specifically its structure, mechanical properties, Young’s modulus, and superelasticity. In this study, plates of the Ti-38Zr-(8-10)Nb (at. %) alloy were investigated after quenching and subsequent annealing. In Ti-38Zr-(8-10)Nb alloys, quenching from 600 °C fixes the β-phase of Ti. In alloys with (8-9)Nb, this is a metastable β-phase, as evidenced by its superelastic behavior under cyclic tension. Annealing at 400 °C leads to a clear decomposition of the quenched high-temperature β-phase in Ti-38Zr-(8-9)Nb alloys into β- and α′-phases. Based on the mechanical test results, it can be inferred that the precipitation of the brittle ω-phase and the α′-phase occur concurrently, since annealing at 400 °C causes a pronounced embrittlement of the Ti-38Zr-(8–9)Nb alloys (with elongation dropping from ~15% to 0.7–2.5%, respectively) alongside a substantial increase in strength (from 500 MPa to 1010 MPa). For the Ti-38Zr-10Nb alloy, the ductility also declines but remains within acceptable limits (from ~14% to ~10%), while the strength rises from 520 MPa to 630 MPa. The Young’s modulus of the Ti-38Zr-(8-10)Nb alloy after quenching is ~80 GPa. After annealing, it increases to 95 GPa for alloys with (8-9)Nb, while for 10Nb it remains at approximately 80 GPa. Full article

(This article belongs to the Section Bone Biomaterials)

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22 pages, 10104 KB

Open AccessEditor’s ChoiceArticle

Biomimetic Chitosan/Polyvinyl Alcohol–Glycerol Scaffolds Inspired by Porcupine Quills for Segmental Bone Defect Repair

by Jingwen Yang, Zihao Zhao, Zengtao Song, Lei Cao, Xifan Mei and Xing Zhang

J. Funct. Biomater. 2026, 17(4), 177; https://doi.org/10.3390/jfb17040177 - 3 Apr 2026

Viewed by 697

Abstract

Segmental bone defects are large, non-healing injuries characterized by insufficient structural support and limited bioactivity, posing a significant clinical challenge. In this study, we developed biomimetic chitosan/polyvinyl alcohol–glycerol (CS/PG) scaffolds inspired by porcupine quills, which were fabricated via fused deposition modeling and unidirectional [...] Read more.

Segmental bone defects are large, non-healing injuries characterized by insufficient structural support and limited bioactivity, posing a significant clinical challenge. In this study, we developed biomimetic chitosan/polyvinyl alcohol–glycerol (CS/PG) scaffolds inspired by porcupine quills, which were fabricated via fused deposition modeling and unidirectional freeze casting. The as-prepared scaffold featured a dense outer layer of polyvinyl alcohol–glycerol (PG) with high compressive strength (24.21 ± 0.11 MPa at 25% strain) and an oriented inner foam of chitosan (CS). The CS foam was further incorporated with poly (3,4-ethylenedioxythiophene) polystyrene sulfonic acid (PEDOT:PSS, denoted as PP) and amorphous zinc phosphate (AZP) to form PP-AZP-CS/PG, aimed at enhancing neural conductivity and stimulating blood vessel formation, respectively. The in vitro results indicated that the biomimetic scaffolds exhibited excellent biocompatibility while significantly enhancing angiogenesis and osteogenesis capabilities. In a rabbit radial segmental defect model, PP-AZP-CS/PG achieved robust bone regeneration, attaining a bone volume/total volume of approximately 26.22% after implantation for 8 weeks. Overall, this biomimetic scaffold demonstrated that integrating hierarchical design with additional bioactive components enhanced mechanical support while promoting new bone regeneration, addressing critical challenges in segmental bone defect repair. Full article

(This article belongs to the Section Bone Biomaterials)

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19 pages, 695 KB

Open AccessEditor’s ChoiceReview

Bone Substitutes in Alveolar Ridge Augmentation: A Narrative Literature Review

by Marija Bubalo, Sanja Dugonjic, Dejan Dubovina, Zdenka Stojanovic, Milka Gardasevic, Jelena Mijatovic, Boban Milovanovic, Milovan Stevic, Milos Stepovic, Dejan Jeremic and Zlata Rajkovic Pavlovic

J. Funct. Biomater. 2026, 17(4), 176; https://doi.org/10.3390/jfb17040176 - 1 Apr 2026

Cited by 1 | Viewed by 1624

Abstract

Adequate alveolar bone volume is a prerequisite for predictable and long-term success in dental implant therapy. Physiological post-extraction remodeling frequently results in horizontal and vertical ridge deficiencies, which may compromise optimal implant placement. Guided bone regeneration (GBR) has become a cornerstone procedure in [...] Read more.

Adequate alveolar bone volume is a prerequisite for predictable and long-term success in dental implant therapy. Physiological post-extraction remodeling frequently results in horizontal and vertical ridge deficiencies, which may compromise optimal implant placement. Guided bone regeneration (GBR) has become a cornerstone procedure in implant dentistry, with clinical outcomes largely influenced by the biological and mechanical characteristics of grafting materials. Different bone grafts and their combinations are currently clinically applicable, each exhibiting distinct osteogenic, osteoinductive, and osteoconductive properties, as well as varying resorption profiles and volumetric stability. This narrative review aims to analyze the biological principles of alveolar ridge augmentation, compare the properties of commonly used graft materials, evaluate clinical outcomes, and discuss emerging regenerative strategies. Literature published between 2000 and 2025 was assessed to synthesize current evidence regarding graft integration, bone formation, desorption dynamics, and clinical indications. Autogenous bone remains the gold standard due to its combined osteogenic, osteoinductive, and osteoconductive potential; however, its limitations have driven the development of alternative materials, including allografts, xenografts, alloplastic substitutes, demineralized tooth matrices, platelet concentrates, and customized scaffolds. While no single material is universally ideal, appropriate selection based on defect characteristics and clinical objectives is essential for predictable outcomes. Future research should prioritize long-term comparative trials, biomaterial standardization, and biologically enhanced regenerative approaches. 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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22 pages, 728 KB

Open AccessEditor’s ChoiceReview

Protein-Encoding Chemically Modified mRNAs for Musculoskeletal Tissue Regeneration and Repair

by Britney S. Force, Xueqin Gao and Johnny Huard

J. Funct. Biomater. 2026, 17(4), 167; https://doi.org/10.3390/jfb17040167 - 1 Apr 2026

Cited by 1 | Viewed by 1197

Abstract

Musculoskeletal disorders and injuries are highly prevalent and encompass a broad range of conditions, including bone fractures and segmental defects, tendinopathies and tendon injury, and cartilage disorders such as osteoarthritis, cartilage defects, and intervertebral disc disease. These conditions can arise from diverse causes [...] Read more.

Musculoskeletal disorders and injuries are highly prevalent and encompass a broad range of conditions, including bone fractures and segmental defects, tendinopathies and tendon injury, and cartilage disorders such as osteoarthritis, cartilage defects, and intervertebral disc disease. These conditions can arise from diverse causes including trauma and injury, tumor resection, congenital abnormalities, and age-related degeneration. In the past decades, administration of chemically modified mRNA (cmRNA) encoding growth factors and transcriptional regulators has demonstrated effectiveness in repairing musculoskeletal tissues in preclinical studies. This review summarizes recent advancements in bone, tendon, cartilage, intervertebral disc, and muscle regeneration achieved through the localized delivery of protein-encoding mRNAs to express therapeutic target proteins. Delivery of cmRNA encoding growth factors such as BMP-2, BMP-9, VEGF, FGF-18, and IGF-1, or transcriptional regulators including Runx1, to various animal models has shown beneficial effects on bone, tendon, cartilage, and muscle injury repair in preclinical models. Alongside these progresses, the advantages and disadvantages of applying chemically modified mRNA for musculoskeletal tissue regeneration are also discussed. While studies show the promise of cmRNA for therapeutic applications in orthopedic tissue regeneration, more research is required to optimize growth factors and delivery methods, as well as validate long-term safety and efficacy prior to successful translation into new therapies to benefit patients. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Bone Tissue Engineering)

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21 pages, 3832 KB

Open AccessEditor’s ChoiceArticle

Characterization of Argopecten purpuratus Shells as Marine-Derived Bioceramics: Microstructural and Biological Insights for Tissue Engineering Applications

by Carola Millán, Isabel Benjumeda-Wijnhoven, José I. Contreras Raggio, Astrid Muñoz, Ignacia Muñoz-Brautigam, María F. Álamos, Marco A. Lardies, Juan F. Santibañez, Nelson A. Lagos and Juan F. Vivanco

J. Funct. Biomater. 2026, 17(4), 164; https://doi.org/10.3390/jfb17040164 - 1 Apr 2026

Viewed by 1134

Abstract

This study presents a comprehensive characterization of Argopecten purpuratus (AP) shells—a marine-derived natural bioceramic composed predominantly of calcium carbonate (CaCO₃)—to evaluate their potential as biomaterials for regenerative medicine. Structural and compositional analyses were performed using micro-computed tomography (MicroCT), scanning [...] Read more.

This study presents a comprehensive characterization of Argopecten purpuratus (AP) shells—a marine-derived natural bioceramic composed predominantly of calcium carbonate (CaCO₃)—to evaluate their potential as biomaterials for regenerative medicine. Structural and compositional analyses were performed using micro-computed tomography (MicroCT), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). These techniques confirmed a high CaCO₃ content (>96 wt%) and revealed distinct microstructural features: the outer surface showed irregular grooves and rough textures, while the inner surface exhibited smoother, foliated morphologies with mixed calcite and aragonite phases. To assess biocompatibility, human gingival mesenchymal stem cells (hGMSCs) were cultured on both shell surfaces. Viability and adhesion were evaluated via MTS assays and fluorescence microscopy at time points ranging from 30 min to four weeks. Both surfaces supported robust early metabolic activity and long-term proliferation, with cells covering the entire surface area after four weeks. Morphometric analysis indicated time-dependent changes in cell shape, transitioning from rounded to elongated morphologies, with minor differences linked to surface topography. The integration of structural, compositional, and biological data demonstrates that AP shells provide a cytocompatible and sustainable natural material platform capable of supporting cell adhesion and proliferation. Their inherent micro- and nanoscale surface features may facilitate protein adsorption and cell–material interactions. These findings highlight the importance of correlating microstructural material properties with cellular responses and support the future exploration of marine-derived bioceramics for regenerative medicine applications. Full article

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

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21 pages, 6900 KB

Open AccessEditor’s ChoiceArticle

Nerve Guidance Conduit Prepared from Decellularized Small Intestine for Nerve Repair

by Xiang-Ting Huang, Ying-Chih Lin, Ling-Yun Cheng, Yi-Dan Chang and Wen-Yu Su

J. Funct. Biomater. 2026, 17(4), 170; https://doi.org/10.3390/jfb17040170 - 1 Apr 2026

Cited by 1 | Viewed by 951

Abstract

Braided nerve guidance conduits (NGCs) composed of decellularized porcine small intestinal submucosa (SIS) were developed to achieve an appropriate balance between mechanical performance and biological compatibility for peripheral nerve repair. This study aimed to compare four SIS-braided conduits with silicone tubes in terms [...] Read more.

Braided nerve guidance conduits (NGCs) composed of decellularized porcine small intestinal submucosa (SIS) were developed to achieve an appropriate balance between mechanical performance and biological compatibility for peripheral nerve repair. This study aimed to compare four SIS-braided conduits with silicone tubes in terms of bending compliance, tensile strength, swelling behavior, and cytocompatibility. SIS-braided conduit exhibited a favorable combination of flexibility, tensile strength, and dimensional stability. In vitro evaluations using PC12 and SW10 cells demonstrated that SIS-braided conduit supported neurite outgrowth and Schwann cell adhesion, confirming its favorable cytocompatibility. Based on these findings, SIS-braided conduits and silicone tubes were subsequently evaluated in a rat sciatic nerve defect model. Functional recovery assessed using the Sciatic Functional Index suggested preliminary functional recovery in the SIS-braided conduit, and histological analyses revealed evidence of axonal regeneration and myelin formation within the conduit. Overall, the results indicate that the integration of mechanical robustness with biological activity is essential for the design of nerve graft substitutes. The conduit braided from decellularized small intestinal submucosa represents a promising biodegradable alternative, a considerable biodegradable alternative to conventional non-degradable silicone conduits for peripheral nerve repair. Full article

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

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14 pages, 1969 KB

Open AccessEditor’s ChoiceArticle

Biological Impact of Extrusion Bioprinting Nasoseptal Chondrocytes for Tissue Engineering Applications

by Thomas Harry Jovic, Josh Roberts, Feihu Zhao, Shareen Heather Doak and Iain Stuart Whitaker

J. Funct. Biomater. 2026, 17(4), 163; https://doi.org/10.3390/jfb17040163 - 1 Apr 2026

Cited by 1 | Viewed by 650

Abstract

Shear stress is a significant consideration in 3D bioprinting systems, with implications for cell viability and behaviour. This study hypothesised that relevant levels of shear stress would be generated during the process of 3D bioprinting human nasoseptal chondrocytes in a nanocellulose alginate bioink, [...] Read more.

Shear stress is a significant consideration in 3D bioprinting systems, with implications for cell viability and behaviour. This study hypothesised that relevant levels of shear stress would be generated during the process of 3D bioprinting human nasoseptal chondrocytes in a nanocellulose alginate bioink, with implications for cell viability and chondrogenic gene expression. Through a combined approach of in silico modelling and in vitro testing, we assessed chondrocyte viability and gene expression immediately within the first 72 h post-printing. Cell viability was determined using live–dead, alamarBlue and lactate dehydrogenase assays immediately and 24 h post-printing compared to cell-only and unprinted cell–biomaterial controls. Gene expression analysis of Type 2 collagen, SOX9, aggrecan and alkaline phosphatase gene expression was performed 4 h and 72 h post-printing. Computational fluid dynamics predicted a shear stress of 292 Pa and maximum fluid velocity of 19 mm/s during the bioprinting process. No statistically significant cell death or cell lysis was detected between groups immediately post-printing; however, statistically significant chondrocyte cell death was observed at 24 h in the printed group (p = 0.047). Moreover, the bioprinting process evoked a transient initial rise in both chondrogenic (SOX9, aggrecan) and osteogenic gene expression (ALP) with a marked suppression in type 2 collagen expression at 72 h (0.05, p = 0.0005), indicating biological effects evoked by shear stress during printing. This study highlights the importance of optimising the bioprinting process to facilitate low shear stress conditions for durable cartilage tissue engineering. Full article

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

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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 1521

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 1818

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

Cited by 1 | Viewed by 1469

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

Viewed by 1159

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 1418

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

Cited by 1 | Viewed by 1382

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

Cited by 1 | Viewed by 1353

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 1716

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 1129

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 1931

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 1141

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 4 | Viewed by 954

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 3 | Viewed by 1508

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 1634

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

Cited by 1 | Viewed by 1275

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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