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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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17 pages, 7531 KB  
Article
L-Serine–Incorporated Collagen Scaffolds for Modulating In Vivo Degradation Behavior
by Su-Young Kim, Ji-Hyeon Oh, Min-Ho Hong, Joon Ha Lee, You-Young Jo and Seong-Gon Kim
J. Funct. Biomater. 2025, 16(12), 466; https://doi.org/10.3390/jfb16120466 - 18 Dec 2025
Viewed by 655
Abstract
Collagen-based biomaterials are widely used, but their relatively rapid biodegradation can limit functional duration. Such collagen constructs are widely used as barrier membranes in guided tissue and bone regeneration, where controlled degradation is essential for maintaining function. Although conventional crosslinking methods extend stability, [...] Read more.
Collagen-based biomaterials are widely used, but their relatively rapid biodegradation can limit functional duration. Such collagen constructs are widely used as barrier membranes in guided tissue and bone regeneration, where controlled degradation is essential for maintaining function. Although conventional crosslinking methods extend stability, they may introduce cytotoxicity, alter mechanical behavior, or hinder tissue integration. This study evaluated whether incorporating L-serine, a polar amino acid capable of hydrogen bonding, could modulate collagen structure and slow degradation without chemical crosslinking. L-Serine was selected because its hydroxyl-containing side chain can engage in biocompatible, hydrogen-bond–mediated interactions that offer a mild, non-crosslinking means of stabilizing collagen. Collagen scaffolds, prepared by incorporating L-serine into a collagen hydrogel followed by drying, were produced with 0–40 wt% L-serine and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, circular dichroism, and scanning electron microscopy. In vivo degradation was assessed in a subcutaneous mouse model comparing unmodified collagen, collagen containing 40 wt% L-serine, and a commercially available bilayer porcine collagen membrane (Bio-Gide®, composed of type I and III collagen), with residual area quantified by serial sonography and histological evaluation. Low-to-moderate L-serine incorporation preserved triple-helical features, while 40 wt% led to crystalline domain formation and β-sheet enrichment. L-serine–treated collagen exhibited significantly greater residual area (2.70 ± 1.45 mm2) than unmodified collagen (0.37 ± 0.22 mm2, p < 0.05), although Bio-Gide® remained the most persistent (5.64 ± 2.76 mm2). These findings demonstrate that L-serine incorporation can modulate collagen structure and degradation kinetics through a simple, aqueous, and non-crosslinking approach. The results provide preliminary feasibility data supporting amino acid–assisted tuning of collagen resorption properties and justify further evaluation using membrane-specific fabrication and application-relevant testing. Full article
(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)
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15 pages, 2354 KB  
Article
3D-Printed Multifunctional Multicompartment Polymer-Based Capsules for Tunable and Spatially Controlled Drug Release
by Antonio Minopoli, Giordano Perini, Davide Evangelista, Matteo Marras, Alberto Augello, Valentina Palmieri, Marco De Spirito and Massimiliano Papi
J. Funct. Biomater. 2025, 16(12), 456; https://doi.org/10.3390/jfb16120456 - 8 Dec 2025
Viewed by 774
Abstract
The development of polymer-based systems is central to the design of next-generation drug delivery carriers, as polymers enable versatile tuning of physicochemical properties and responsiveness. In this work, we introduce a 3D printing-based strategy for the fabrication of multicompartment capsules that integrate multiple [...] Read more.
The development of polymer-based systems is central to the design of next-generation drug delivery carriers, as polymers enable versatile tuning of physicochemical properties and responsiveness. In this work, we introduce a 3D printing-based strategy for the fabrication of multicompartment capsules that integrate multiple polymers within a unique one-step process. This approach allows precise spatial organization and structural complexity, yielding capsules with customizable features such as compartmentalization, polymer-specific responsiveness, and localized release control. In particular, pH-triggered release can be programmed across distinct polymeric regions of the capsules, enabling site-specific delivery along different intestinal segments, including the small intestine and colon. The use of 3D printing thus provides a scalable and adaptable platform to generate multifunctional polymer-based carriers with finely tunable drug release profiles, paving the way for new directions in polymer-enabled controlled delivery technologies. Full article
(This article belongs to the Special Issue Polymer-Based Materials in Biomedical Applications)
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16 pages, 1608 KB  
Article
Injectable Piezoelectric Hydrogel for Vital Pulp Therapy
by Varun Solanki, Carolina Montoya, Prasanna Neelakantan, Maobin Yang and Santiago Orrego
J. Funct. Biomater. 2025, 16(12), 452; https://doi.org/10.3390/jfb16120452 - 5 Dec 2025
Viewed by 1148
Abstract
Vital pulp therapy (VPT) seeks to preserve pulp vitality by using biocompatible with regenerative potential. This study tested the hypothesis that an injectable gelatin methacryloyl (GelMA) hydrogel containing piezoelectric barium titanate promotes odontogenic differentiation of dental pulp stem cells (DPSC) significantly better than [...] Read more.
Vital pulp therapy (VPT) seeks to preserve pulp vitality by using biocompatible with regenerative potential. This study tested the hypothesis that an injectable gelatin methacryloyl (GelMA) hydrogel containing piezoelectric barium titanate promotes odontogenic differentiation of dental pulp stem cells (DPSC) significantly better than a commercially available tricalcium silicate material used for vital pulp therapy. First, the light-curable, injectable piezoelectric hydrogel was engineered and characterized for its physicomechanical, piezoelectric properties and biocompatibility to DPSCs. The effect of this gel on the odontogenic differentiation of DPSCs was determined by measuring the expression level of key genes, compared to Biodentine XP. The hydrogel exhibited excellent injectability (<1 kgf of force), mechanical stability, and generated physiologically relevant voltages under cyclic loading mimicking mastication. MTT and ROS assays show no cytotoxic or damaging oxidative stress effects. When DPSCs were cultured over the materials under cyclic loading, the piezoelectric hydrogel significantly enhanced cell viability and upregulated COL1A1, DSPP, and DMP1 expression compared to Biodentine XP and non-piezoelectric hydrogel controls. These findings establish piezoelectric hydrogel as a self-powered, bioactive platform that converts physiological forces into regenerative bioelectric cues, offering a promising next-generation material for vital pulp therapy. Full article
(This article belongs to the Special Issue Advanced Biomaterials and Engineered Systems in Endodontics)
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12 pages, 1447 KB  
Article
Three-Dimensional Bioprinting of Regenerative Cartilage Constructs with Directional Ionically Derived Stiffness Gradients
by Maryam Hosseini, Angeliki Dimaraki, Gerjo. J. V. M. van Osch, Lidy E. Fratila-Apachitei, Pedro J. Díaz-Payno and Amir A. Zadpoor
J. Funct. Biomater. 2025, 16(12), 451; https://doi.org/10.3390/jfb16120451 - 3 Dec 2025
Cited by 1 | Viewed by 2468
Abstract
Tissue engineering approaches for cartilage tissue regeneration are expanding to include the complex features of the tissue, such as the biological and mechanical gradients. Many of these approaches are, however, based on the use of multiple biomaterials or concentrations, and crosslinking methods that [...] Read more.
Tissue engineering approaches for cartilage tissue regeneration are expanding to include the complex features of the tissue, such as the biological and mechanical gradients. Many of these approaches are, however, based on the use of multiple biomaterials or concentrations, and crosslinking methods that make it difficult to integrate and control the properties of the resulting scaffolds. In this study, a 3D bioprinted scaffold with a stiffness gradient was fabricated by using a single biomaterial type and concentration combined with a directional ionic crosslinking method. The scaffolds revealed a gradient in stiffness from 39.8 ± 6.6 kPa at the top to 60.6 ± 10.9 kPa at the bottom of the scaffolds. Live/dead analysis of human chondrocytes embedded in the scaffolds showed no negative effects of the stiffness gradient on cell viability over 28 days. The induced stiffness gradient led to a gradient in cell density and sulfated glycosaminoglycan deposition in the bioprinted tissue constructs with enhanced values in the softer top region of the scaffolds as compared to the stiffer bottom part. This study showed a novel method to generate scaffolds with stiffness gradients from a single biomaterial and indicates that such scaffolds could be used to spatially regulate the behavior of chondrocytes and the associated deposition of the cartilage matrix. Full article
(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)
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28 pages, 18645 KB  
Article
Biomimetic Glycosaminoglycan-Enriched Electrospun Polymeric Scaffolds for Enhanced Early Tissue Regeneration
by Morgane Meyer, Rana Smaida, Henri Favreau, Cristina Yus, Hervé Gegout, Manuel Arruebo, Nadia Bahlouli, Guy Ladam, Guillaume Conzatti, Stephan Lemmens, Guoqiang Hua, Florence Fioretti and Nadia Benkirane-Jessel
J. Funct. Biomater. 2025, 16(12), 447; https://doi.org/10.3390/jfb16120447 - 29 Nov 2025
Viewed by 904
Abstract
Implantable scaffolds are increasingly recognized as transformative tools in regenerative medicine, offering the potential to prevent or mitigate tissue degeneration. Osteoarthritis is a widespread degenerative joint disease that often progresses from early focal lesions to severe joint damage, creating substantial clinical and socioeconomic [...] Read more.
Implantable scaffolds are increasingly recognized as transformative tools in regenerative medicine, offering the potential to prevent or mitigate tissue degeneration. Osteoarthritis is a widespread degenerative joint disease that often progresses from early focal lesions to severe joint damage, creating substantial clinical and socioeconomic burdens. Preventive strategies for early-stage lesions remain limited. This study reports the design and development of a functional polymeric scaffold intended to support early tissue regeneration and potentially prevent lesion progression. The scaffold consists of an electrospun poly (ε-caprolactone) nanofibrous membrane enriched with glycosaminoglycans, including hyaluronic acid and chondroitin sulfate, to mimic essential features of the cartilage extracellular matrix and provide a supportive microenvironment. Complete structural, physicochemical, and mechanical characterization was performed to assess the scaffold architecture, stability, hydration properties, and suitability for tissue environments. In vitro investigations were conducted to evaluate cytocompatibility and the interaction of the scaffold with relevant cell types. The scaffold is designed as a potential future preventive strategy to support cartilage integrity and limit disease progression. This approach represents a promising strategy to preserve joint integrity and function, addressing a critical unmet clinical need and enabling translation toward clinical application. Full article
(This article belongs to the Special Issue Materials and Techniques for Bone Tissue Engineering: From Scaffolds to Complex Matrices)
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29 pages, 5971 KB  
Review
The Ballet of Natural-Product: Carrier-Free “Triadic” Drug Delivery Platforms for Enhanced Tumor Treatment
by Liyan Yang and Zhonglei Wang
J. Funct. Biomater. 2025, 16(12), 433; https://doi.org/10.3390/jfb16120433 - 25 Nov 2025
Cited by 1 | Viewed by 1279
Abstract
Cancer poses a considerable challenge to global public health and stands as the second leading cause of mortality worldwide. Chemotherapy provides limited benefits for advanced-stage cancer, mainly due to high systemic toxicity and drug resistance. Optimal cancer treatment requires a sophisticated, multidisciplinary collaboration [...] Read more.
Cancer poses a considerable challenge to global public health and stands as the second leading cause of mortality worldwide. Chemotherapy provides limited benefits for advanced-stage cancer, mainly due to high systemic toxicity and drug resistance. Optimal cancer treatment requires a sophisticated, multidisciplinary collaboration aimed at extending survival, enhancing quality of life, and reducing toxicity. Natural products present advantages, including a wide array of structural diversity, reduced toxicity, improved immune modulation, and the ability to act on multiple targets. Nanomedicine design shows promise in tumor treatment and diagnosis by improving efficacy and minimizing side effects. Due to the heterogeneity of tumors in genetics, metabolism, and microenvironment, natural product-based carrier-free drug delivery platforms have been actively investigated and demonstrated considerable potential for enhanced tumor treatment. “Triadic” strategies can simultaneously perform various functions on a carrier-free intelligent nanoplatform. These include combinational chemotherapy, photodynamic therapy (PDT) with bioimaging and chemotherapy, PDT combined with photothermal therapy (PTT) and chemotherapy, chemo-radio-theranostics, as well as gene therapy (GT) in conjunction with PTT and chemotherapy. This multifaceted approach enhances therapeutic efficacy, reduces multidrug resistance, and minimizes systemic toxicity. This review encompasses recent advancements in cancer therapy using carrier-free “triadic” nanomedicines based on natural products (between 2024 and 2025) and evaluates this evolving field, emphasizing the pivotal role of natural products—berberine, camptothecin, hypericin, erianin, curcumin, lactose, paclitaxel, gambogic acid, and glycyrrhizic acid—in drug delivery platforms. Furthermore, it addresses the challenges and bottlenecks encountered by carrier-free drug delivery platforms, offering valuable insights into their development trajectories. Full article
(This article belongs to the Special Issue 15th Anniversary of JFB—Advanced Biomaterials for Drug Delivery)
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24 pages, 1622 KB  
Review
An Overview of 3D Bioprinting Impact on Cell Viability: From Damage Assessment to Protection Solutions
by Sara Manzoli, Elena Merotto, Martina Piccoli, Pierangelo Gobbo, Silvia Todros and Piero G. Pavan
J. Funct. Biomater. 2025, 16(12), 436; https://doi.org/10.3390/jfb16120436 - 25 Nov 2025
Cited by 4 | Viewed by 1810
Abstract
Three-dimensional (3D) bioprinting has become a widely exploited tissue engineering technique for producing functional constructs that can mimic and replace native tissues. To this end, different printing strategies can be adopted, including inkjet-based, light-assisted, and extrusion-based bioprinting. Despite the great improvements that these [...] Read more.
Three-dimensional (3D) bioprinting has become a widely exploited tissue engineering technique for producing functional constructs that can mimic and replace native tissues. To this end, different printing strategies can be adopted, including inkjet-based, light-assisted, and extrusion-based bioprinting. Despite the great improvements that these innovative techniques introduce, cell viability maintenance during and after the bioprinting process remains a challenging open question. Indeed, the reduction in cell viability is generally related to several crucial conditions during printing, such as high shear stresses and a nutrient-deficient environment of printed constructs. In this work, the current literature on 3D bioprinting technologies is reviewed, focusing on the level of cell damage that can be imparted during biomaterial printing. In particular, extrusion bioprinting, extrusion-associated shear stress and its impact on cell viability are described in detail. The simulation of the bioprinting process through computational fluid dynamics is proposed as an appropriate method to analyze the parameters involved during bioprinting. Moreover, the viability of cells encapsulated into bioink is discussed, as well as literature techniques aimed at enhancing it by both biomaterial modifications and cell micro-encapsulation. Full article
(This article belongs to the Special Issue 3D Bioprinting for Tissue Engineering and Regenerative Medicine)
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19 pages, 7795 KB  
Article
Endothelial Cells Differentiated from Human Induced Pluripotent Stem Cells Form Aligned Network Structures in Engineered Neural Tissue
by Poppy O. Smith, Parmjit Jat and James B. Phillips
J. Funct. Biomater. 2025, 16(11), 425; https://doi.org/10.3390/jfb16110425 - 20 Nov 2025
Viewed by 1224
Abstract
Background/Objectives: Endothelial cells play a key role in peripheral nerve regeneration, forming aligned vasculature which bridges the gap in the injured nerve tissue and guides the regrowing tissue. This work aimed to mimic key features of this aligned vasculature by differentiating endothelial cells [...] Read more.
Background/Objectives: Endothelial cells play a key role in peripheral nerve regeneration, forming aligned vasculature which bridges the gap in the injured nerve tissue and guides the regrowing tissue. This work aimed to mimic key features of this aligned vasculature by differentiating endothelial cells from human induced pluripotent stem cells (hiPSCs) and incorporating them into engineered neural tissue (EngNT). Methods: hiPSCs were differentiated into endothelial cells with the temporal addition of growth factors and biomolecules. These hiPSC-derived endothelial cells (hiPSC-ECs) were incorporated into EngNT fabricated from collagen hydrogels using the gel aspiration-ejection (GAE) technique and maintained in vitro to allow endothelial network formation. Results: At the mRNA and protein level, pluripotency marker expression decreased and endothelial cell marker expression increased over the course of hiPSC differentiation to endothelial cells. The derived endothelial cells expressed CD31, CD144, ENG, VEGFR2, and VWF, and formed network structures in the matrix tubulogenesis assay. hiPSC-ECs incorporated into EngNT were viable and aligned. They formed highly aligned tube-like structures containing lumens after four days in culture and the EngNT constructs supported neurite growth in vitro when co-cultured with rat dorsal root ganglion (DRG) neurons. Conclusions: This work rapidly generated engineered nerve tissue containing highly aligned endothelial tube-like structures, resembling key features of the early nerve regeneration bridge. Therefore, this 3D engineered tissue provides a platform to study the effects of endothelial cell structures in nerve repair treatment and translational development. Full article
(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)
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32 pages, 19195 KB  
Article
Suitability of Mg-Nd and Mg-Zn Alloys to Obtain Biodegradable Structures for Bone Defects
by Veronica Manescu (Paltanea), Aurora Antoniac, Maria Cristina Moraru, Iulian Antoniac, Cosmin Mihai Cotrut, Sebastian Gradinaru, Alexandra Iulia Dreanca, Bogdan Sevastre, Romelia Pop, Flaviu Alexandru Tabaran, George Mihail Vlasceanu, Mariana Ionita and Marius Manole
J. Funct. Biomater. 2025, 16(11), 423; https://doi.org/10.3390/jfb16110423 - 12 Nov 2025
Cited by 1 | Viewed by 1529
Abstract
Mg-based alloys are one of the most promising materials used in regenerative medicine for bone tissue engineering. Considering the increasing prevalence of a continuously aging population, as well as the high incidence of accidents and bone cancers, it is crucial to explore biomaterials [...] Read more.
Mg-based alloys are one of the most promising materials used in regenerative medicine for bone tissue engineering. Considering the increasing prevalence of a continuously aging population, as well as the high incidence of accidents and bone cancers, it is crucial to explore biomaterials that can serve as bone substitutes. After carefully analyzing the literature in the introduction section, we proposed two Mg-based alloys as suitable for obtaining biodegradable structures for bone defect treatment. To achieve trustworthy results, the alloys’ microstructure was investigated using microscopic techniques coupled with energy-dispersive spectroscopy and X-ray diffraction. The obtained results were comparable with those described in references on similar Mg alloys. Then, the mechanical compression properties were highlighted, and the in vitro corrosion behavior proved that Mg-Zn exhibited a reduced corrosion rate compared to the Mg-Nd alloy, as tested using electrochemical methods. However, the in vivo tests showed good biocompatibility for both magnesium alloys. In conclusion, both alloys are suitable for use as potential bone substitute applications, but it must be taken into consideration that Mg-Zn alloys present lower biodegradation and mechanical properties. For future investigations, we aim to develop bone substitutes made from these materials, specifically designed for small bone defect treatment and with patient-adapted geometry. Due to the differences mentioned above, various designs will be tested. Full article
(This article belongs to the Special Issue The 15th Anniversary of JFB—Functional Biomaterials: Bioactive Properties and Medical Applications)
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55 pages, 17120 KB  
Review
Magnetic Hydrogels as a Treatment for Oncological Pathologies
by Veronica Manescu (Paltanea), Adrian-Vasile Dumitru, Aurora Antoniac, Iulian Antoniac, Gheorghe Paltanea, Elena-Cristina Zeca (Berbecar), Mirela Gherghe, Iosif Vasile Nemoianu, Alexandru Streza, Costel Paun and Sebastian Gradinaru
J. Funct. Biomater. 2025, 16(11), 414; https://doi.org/10.3390/jfb16110414 - 5 Nov 2025
Viewed by 2008
Abstract
Cancer is considered today as a prevalent research direction due to the fact that, by 2050, more than 30 million cases will occur, followed by about 19 million deaths. It is expected that scholars will search for new, innovative, and localized therapies to [...] Read more.
Cancer is considered today as a prevalent research direction due to the fact that, by 2050, more than 30 million cases will occur, followed by about 19 million deaths. It is expected that scholars will search for new, innovative, and localized therapies to ensure a much more targeted treatment with reduced side effects. Magnetic hydrogels overcome the disadvantages of classical magnetic nanoparticles in various oncological domains, including magnetic hyperthermia, theragnostic, immunotherapy, and, notably, regenerative medicine and contrast substances. We will review the magnetic hydrogel topics that may be involved as a potential application for cancer. Firstly, we present the international context and subject importance in the framework of statistics estimated by some researchers. Then, the magnetic hydrogel synthesis method will be briefly described with examples extracted from the literature. Supplementary, we will emphasize the main attributes of an ideal magnetic hydrogel, and last but not least, we will review some of the latest in vitro and in vivo studies in a direct relationship with magnetic hyperthermia, chemotherapeutic drug release dynamics, and immunotherapy used as single strategies or in combination, by underling the magnetic properties of the hydrogels and importance of application of magnetic fields. We will conclude our review paper by discussing toxicity issues, future trends, limitations, and proposed new approaches to address them. Full article
(This article belongs to the Special Issue Advances in Multifunctional Hydrogels for Biomedical Application (2nd Edition))
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16 pages, 10746 KB  
Article
Pre-Vascularized 3-Dimensional Skin Substitutes Promote Angiogenesis and Tissue Repair in a Murine Model of Refractory Skin Ulcers
by Shota Tojo, Hiromi Miyazaki, Takami Saiki, Yasuyuki Tsunoi, Shingo Nakamura and Ryuichi Azuma
J. Funct. Biomater. 2025, 16(11), 409; https://doi.org/10.3390/jfb16110409 - 3 Nov 2025
Cited by 1 | Viewed by 1184
Abstract
Restoring blood flow is crucial for treating refractory ulcers. Despite advancements in various biomaterials, none incorporating pre-formed blood vessels have been commercialized. To address this, we developed a pre-vascularized three-dimensional (3D) skin substitute (PV-3D skin) designed to enhance healing when treating refractory ulcers. [...] Read more.
Restoring blood flow is crucial for treating refractory ulcers. Despite advancements in various biomaterials, none incorporating pre-formed blood vessels have been commercialized. To address this, we developed a pre-vascularized three-dimensional (3D) skin substitute (PV-3D skin) designed to enhance healing when treating refractory ulcers. This study aimed to evaluate the therapeutic role of PV-3D skin transplantation in refractory ulcer models, induced by applying mitomycin C to wounds in severe immunodeficient mice. The wounds were then treated with PV-3D skin, non-vascularized 3D skin, skin grafts, or wound dressings. The PV-3D skin group demonstrated healing dynamics comparable to those of the skin graft group, with similar tissue morphology and wound temperature changes. Furthermore, at day 7 post-transplantation, the PV-3D skin group demonstrated significantly higher hypoxia-inducible factor 1-alpha expression levels compared to the 3D skin group. By day 14, the PV-3D skin group exhibited a significantly larger vascular area compared to the 3D skin group. Notably, PV-3D skin treatment stimulated host-derived angiogenesis, thereby enhancing wound healing and reducing the recurrence of refractory ulcers. These results suggest that PV-3D skin transplantation offers a promising therapeutic approach for refractory ulcers, especially in terms of angiogenesis. Full article
(This article belongs to the Special Issue The 15th Anniversary of JFB—Functional Biomaterials: Bioactive Properties and Medical Applications)
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23 pages, 7319 KB  
Article
Corrosion-Modulating Effect of Pharmaceutical Agents in a Hybrid Coating System on Pure Magnesium
by Lara Moreno, Adrián Belarra-Rodriguez, Marta Mohedano, Laura Castro, Margarita Chevalier, Raul Arrabal and Endzhe Matykina
J. Funct. Biomater. 2025, 16(11), 406; https://doi.org/10.3390/jfb16110406 - 30 Oct 2025
Cited by 1 | Viewed by 1236
Abstract
There is a knowledge gap about the effect of pharmaceutical agents on the biodegradation of Mg-based resorbable implants. The present work investigates how three common antibiotics and three anti-inflammatory drugs affect the corrosion of high-purity Mg, with and without ceramic and hybrid ceramic/polymeric [...] Read more.
There is a knowledge gap about the effect of pharmaceutical agents on the biodegradation of Mg-based resorbable implants. The present work investigates how three common antibiotics and three anti-inflammatory drugs affect the corrosion of high-purity Mg, with and without ceramic and hybrid ceramic/polymeric coatings, using electrochemical impedance spectroscopy and hydrogen evolution tests. A Ca-P-Si-based ceramic coating is developed using plasma electrolytic oxidation (PEO), after the AC voltage and frequency parameters are optimized. A hybrid coating included a PEO and a poly(ε-caprolactone) (PCL) top layer formed by dip coating. High-purity Mg exhibited an instantaneous onset of corrosion with a corrosion rate of 90 μm/year after 24 h of immersion in a modified α-MEM. A hybrid PEO/PCL coating prevents the onset of corrosion for at least 5 h and reduces the H2 evolution during the following 90 h by two times by the precipitation of 5–40 μm thick Ca-P surface deposits. Gentamicin, naproxen, streptomycin, ciprofloxacin and paracetamol were found to be corrosion accelerators with respect to bare h.p. Mg, whereas aspirin was found to be an inhibitor. Streptomycin-functionalized PEO/PCL system exhibited an active protection mechanism, triggered upon the release of the coating and substrate cations, associated with the coating defect-blocking action of the insoluble Me(II)-streptomycin chelates. Full article
(This article belongs to the Section Biomaterials for Drug Delivery)
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25 pages, 7146 KB  
Article
Biopolymer Fibers of High Strength and Enhanced Orientation by the Synergy of High/Low Molecular Weight Chitosans in Hybrid Biomaterials Processed by Gel Spinning
by Tuan Anh Tran, Ingo Doench, Arnaud Kamdem Tamo, Shaghayegh Jahangir, Sofia Marquez-Bravo, Pamela Molina, Martin Helmstaedter, Aliuska Morales Helguera, Christian Gorzelanny and Anayancy Osorio-Madrazo
J. Funct. Biomater. 2025, 16(11), 405; https://doi.org/10.3390/jfb16110405 - 29 Oct 2025
Viewed by 1255
Abstract
High-performance spun bionanocomposite fibers, composed of high-molecular-weight chitosan (HMW), low-molecular-weight chitosan “oligomers” (LMW), and cellulose nanofibers (CNFs), were successfully fabricated via gel spinning of viscous aqueous chitosan (CHI) based formulations into a NaOH coagulation bath. The X-ray diffraction (XRD) analysis revealed that the [...] Read more.
High-performance spun bionanocomposite fibers, composed of high-molecular-weight chitosan (HMW), low-molecular-weight chitosan “oligomers” (LMW), and cellulose nanofibers (CNFs), were successfully fabricated via gel spinning of viscous aqueous chitosan (CHI) based formulations into a NaOH coagulation bath. The X-ray diffraction (XRD) analysis revealed that the incorporation of cellulose nanofibers contributed to enhance crystallinity of chitosan in spun fibers. The spinning process, which comprised sequential acidic solubilization, basic neutralization, stretching, and drying steps, produced chitosan/CNF composite fibers with high crystallinity, further enhanced by the incorporation of low molecular weight chitosan. The cellulose nanofibers seem to promote CHI crystallization, by acting as nucleation sites for the nucleation and growth of chitosan crystals, with those latter of LMW further enhancing crystallization and orientation due to higher mobility of shorter polymer chains. Two-dimensional XRD patterns demonstrated the preferential alignment of both CNFs and chitosan crystals along the fiber axis. Increasing the proportion of short-chain chitosan led to a reduction of the viscosity of collodion, facilitating the spinning of solutions with higher polymer concentrations. The X-ray diffraction (XRD) analysis revealed that the addition of low-molecular-weight chitosan (LMW), with an intermediate molecular weight Mw of ~4.4 × 104 g/mol, produced the most significant improvements in the crystallinity index (CrI) and orientation. This structural enhancement corresponded to superior mechanical properties like Young’s modulus, yield stress σy, and stress-at-break σb of the processed composite fibers. By incorporating that intermediate molecular weight chitosan, a Young’s modulus as high as 20 GPa was achieved for the spun composite fibers, which was twice higher than the modulus of around 10 GPa obtained by adding the lowest molecular weight chitosan of Mw ~ 2.9 × 104 g/mol in the composite, and largely above the modulus of around 5 GPa obtained for fiber just spun with chitosan without incorporation of cellulose nanofibers. Full article
(This article belongs to the Section Synthesis of Biomaterials via Advanced Technologies)
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31 pages, 3096 KB  
Review
Implications of Tissue Engineering for Tendon Repair and Regeneration
by Dana Ivanisova, Katarina Bevizova, Sara Vach Agocsova, Lubos Danisovic and Martina Culenova
J. Funct. Biomater. 2025, 16(11), 403; https://doi.org/10.3390/jfb16110403 - 28 Oct 2025
Cited by 1 | Viewed by 4282
Abstract
Tendon injuries affect millions of people globally and are among the most prevalent musculoskeletal conditions, frequently resulting in chronic pain, reduced mobility, and functional impairment. While conservative and surgical treatments are available, limitations such as low healing capacity, scar formation, and reduced biomechanics [...] Read more.
Tendon injuries affect millions of people globally and are among the most prevalent musculoskeletal conditions, frequently resulting in chronic pain, reduced mobility, and functional impairment. While conservative and surgical treatments are available, limitations such as low healing capacity, scar formation, and reduced biomechanics necessitate alternative approaches. Tissue engineering offers a promising solution by combining cells, scaffolds, and bioactive molecules to regenerate tendon tissue. This review presents key concepts and emerging trends, highlighting the cellular components, scaffold materials, and manufacturing processes. Tenocytes and mesenchymal stem cells are fundamental for tissue regeneration, as they synthesize extracellular matrix components and regulate inflammatory responses. Various natural and synthetic polymers have been fabricated into scaffolds that mimic the structure and biomechanics of natural tendons. Composite and hybrid scaffolds are utilized to improve the biocompatibility of natural materials with the mechanical stability of synthetic materials. Advanced technologies, such as electrospinning, freeze-drying, and 3D bioprinting, enable the creation of scaffolds with defined architecture and functional gradients, improving cell alignment, differentiation, and tendon–bone integration. Although promising preclinical data exists, major challenges remain in translating these strategies clinically, particularly vascularization, immune rejection, and mechanical stability. Continued interdisciplinary attempts in biomaterials science, cellular biology, and engineering are crucial to advancing clinically viable tendon tissue engineering. Full article
(This article belongs to the Special Issue Materials and Techniques for Bone Tissue Engineering: From Scaffolds to Complex Matrices)
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31 pages, 12238 KB  
Article
Micropatterning and Nanodropletting of Titanium by Shifted Surface Laser Texturing Significantly Enhances In Vitro Osteogenesis of Healthy and Osteoporotic Mesenchymal Stromal Cells
by Theresia Stich, Francisca Alagboso, Girish Pattappa, Jin Chu, Denys Moskal, Michal Povolný, Maximilian Saller, Veronika Schönitzer, Konstantin J. Scholz, Fabian Cieplik, Volker Alt, Maximilian Rudert, Tomáš Kovářík, Tomáš Křenek and Denitsa Docheva
J. Funct. Biomater. 2025, 16(11), 401; https://doi.org/10.3390/jfb16110401 - 27 Oct 2025
Cited by 1 | Viewed by 1620
Abstract
The key to proper implant integration in bone replacement is to orchestrate the complex interactions between materials and tissues. Moreover, due to the rapid demographic shift towards aging societies and the increase in elderly and osteoporotic patients, it is of great importance that [...] Read more.
The key to proper implant integration in bone replacement is to orchestrate the complex interactions between materials and tissues. Moreover, due to the rapid demographic shift towards aging societies and the increase in elderly and osteoporotic patients, it is of great importance that implant materials are osteointegrative in not only healthy but also compromised bone tissues. Here, titanium (Ti) scaffolds were subjected to shifted laser surface texturing (sLST) using a nanosecond pulsed laser to create an open pore macrotopography with micro-and nano-Ti droplets. In contrast to conventional laser texturing, which leads to high heat accumulation; in sLST, the frequency of laser pulses is low, allowing for resolidification, thereby creating a surface with abundant coverage micro-/nanodroplets. The main objective was to compare the cellular responses of human mesenchymal stromal cells (hMSCs) on sLST-textured Ti surfaces (LT-Ti) for the first time with standard sand-blasted, acid-etched surfaces (SLA-Ti). In-depth analyses of cell survival, proliferation, shape, mineralization, and gene expression were performed. Cell survival/proliferation was found to be similar on both surfaces; however, SEM imaging revealed differences in hMSC morphology. On LT-Ti, cells adopted well-rounded shapes, whereas on SLA-Ti they assumed more planar shapes. Bulk RNA sequencing performed after short-term culture on both surfaces disclosed expression changes in genes such as DUSP6, TNFSF12-TNFSF13 and SULT1A4. Remarkably, the osteogenic differentiation capacity of hMSCs was significantly enhanced on LT-Ti compared to SLA-Ti. Furthermore, aged/osteoporotic donor cohorts showed significantly enhanced matrix mineralization on LT-Ti. In conclusion, our novel results demonstrate that sLST-Ti surfaces are safe, highly biocompatible, can rescue patient-cohort-specific mineralization behavior, and therefore hold great potential for the development into next-generation implants, which are suitable for both the elderly and bone-compromised populations. Full article
(This article belongs to the Section Bone Biomaterials)
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21 pages, 3350 KB  
Article
Multifunctional Peptide-Based Biohybrid for Targeted Reduction of Metastatic Breast Carcinoma-Associated Osteolysis
by Nicole Stadler, Bingjie Gao, Maria Jose Silva, Joscha Borho, Eva Haunschild, Kaloian Koynov, Melanie Haffner-Luntzer, Anita Ignatius, Gilbert Weidinger, Seah Ling Kuan, Tanja Weil and Holger Barth
J. Funct. Biomater. 2025, 16(11), 399; https://doi.org/10.3390/jfb16110399 - 25 Oct 2025
Viewed by 3489
Abstract
Metastatic breast carcinoma (BC) cells are prone to spreading in the bone microenvironment, leading to a vicious cycle between local osteoclast-mediated osteolysis and tumor progression. Therefore, the targeted pharmacological down-modulation of BC cell proliferation as well as osteoclast differentiation and hyperactivity might represent [...] Read more.
Metastatic breast carcinoma (BC) cells are prone to spreading in the bone microenvironment, leading to a vicious cycle between local osteoclast-mediated osteolysis and tumor progression. Therefore, the targeted pharmacological down-modulation of BC cell proliferation as well as osteoclast differentiation and hyperactivity might represent a promising treatment option. We developed a multifunctional peptide nanocarrier combining bioactive EPI-X4 peptides and the Rho-inhibiting C3bot enzyme from Clostridium botulinum. C3bot is preferentially internalized into the cytosol of monocytic cells, including osteoclasts, where it inhibits Rho-mediated signal transduction. However, Rho-mediated cellular processes like migration and cell division can also be inhibited in non-monocytic cells if C3bot is delivered into their cytosol by a nanocarrier. To accomplish this, we designed a supramolecular transporter where one molecule of biotinylated C3bot and three biotinylated entities of the human EPI-X4 peptide-derived CXCR4 antagonist JM173 are assembled on avidin as a central platform. This modular transport system (JM173)3-Avi-C3 down-modulated osteoclast formation and hyperactivity and delivered the therapeutic cargo C3bot successfully into the cytosol of breast cancer cells, where it inhibited Rho. Full article
(This article belongs to the Special Issue Advanced Biomaterials in Cancer Therapeutics and Diagnosis)
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24 pages, 4267 KB  
Article
“Attractive” Treatment for Abdominal Aortic Aneurysm Repair: Magnetic Localization of Silk-Iron Packaged Extracellular Vesicles
by Ande X. Marini, Kiran J. McLoughlin, Amanda R. Pellegrino, Golnaz N. Tomaraei, Bo Li, John A. Curci, Mostafa Bedewy, Justin S. Weinbaum and David A. Vorp
J. Funct. Biomater. 2025, 16(11), 395; https://doi.org/10.3390/jfb16110395 - 22 Oct 2025
Viewed by 1753
Abstract
Abdominal aortic aneurysm (AAA) is a dilatation of the distal aorta to a diameter of 50% or more of its normal size of about 2 cm. Risk of aortic rupture can be nearly eliminated with either open surgery or endovascular repair. Procedural risks [...] Read more.
Abdominal aortic aneurysm (AAA) is a dilatation of the distal aorta to a diameter of 50% or more of its normal size of about 2 cm. Risk of aortic rupture can be nearly eliminated with either open surgery or endovascular repair. Procedural risks limit the value of these interventions unless the diameter of the aneurysm has reached a critical threshold (established as 5.5 cm in men or 5.0 cm in women). Thus, patients are monitored until this threshold is reached. Approximately 80% of small AAA will grow and exceed the threshold, providing a therapeutic window for altering this natural history and reducing the risk of rupture. Previous work in our lab has utilized adipose-derived mesenchymal stem cells (ASCs) to treat AAA in vivo, preserving elastic fibers and slowing aneurysm expansion. This work sought to create a delivery system for therapeutic extracellular vesicles (ASC-EVs) secreted by ASCs. Our delivery system incorporated the biocompatibility of regenerated silk fibroin (RSF), the magnetic moveability of iron oxide nanoparticles (IONPs), and the regenerative nature of ASC-EVs to create silk-iron packaged extracellular vesicles (SIPEs). Using this system, we tested the ability to magnetically localize the SIPEs and release their encapsulated ASC-EVs to exert their regenerative effects in vitro. We were successful in magnetically localizing the SIPEs in vitro and silk-iron microparticles (SIMPs) in vivo and in detecting their releasates via flow cytometry and cellular uptake assays. However, while their releasates were detected, their biological effects were diminished compared to unencapsulated controls. Thus, additional optimization related to loading efficiency is needed. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering: Current Status and Advances)
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14 pages, 2210 KB  
Article
Antibacterial PEEK-Ag Surfaces: Development and In Vitro Evaluation Against Staphylococcus aureus and Pseudomonas aeruginosa
by Flávio Rodrigues, Mariana Fernandes, Filipe Samuel Silva, Óscar Carvalho and Sara Madeira
J. Funct. Biomater. 2025, 16(10), 388; https://doi.org/10.3390/jfb16100388 - 16 Oct 2025
Viewed by 1107
Abstract
In the pursuit of addressing the persistent challenge of bacterial adhesion and biofilm formation in dental care, this study investigates the efficacy of electric current as an alternative strategy, specifically focusing on its application in dental contexts. Polyether ether ketone (PEEK), known for [...] Read more.
In the pursuit of addressing the persistent challenge of bacterial adhesion and biofilm formation in dental care, this study investigates the efficacy of electric current as an alternative strategy, specifically focusing on its application in dental contexts. Polyether ether ketone (PEEK), known for its excellent biocompatibility and resistance to bacterial plaque, was enhanced with conductive properties by incorporating silver (Ag), a well-known antibacterial material. Through systematic in vitro experiments, the effectiveness of alternating current (AC) and direct current (DC) in reducing bacterial proliferation was evaluated. The tests were conducted using two bacterial strains: the Gram-positive Staphylococcus aureus and the Gram-negative Pseudomonas aeruginosa. Various configurations, current parameters, and two different electrode configurations were assessed to determine their impact on bacterial reduction. A notable finding from this study is that alternating current (AC) demonstrates superior efficacy compared to direct current (DC). The more significant decrease in CFUs/mL for P. aeruginosa with AC was recorded at the current levels of 5 mA and 500 nA. In opposition, S. aureus exhibited the greatest reduction at 5 mA and 1 mA. This study highlights the potential of using electric current within specific intensity ranges as an alternative strategy to effectively mitigate bacterial challenges in dental care. Full article
(This article belongs to the Section Antibacterial Biomaterials)
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16 pages, 3494 KB  
Article
Fibronectin- and Bioactive Glass-Modified Alginate Scaffolds Support Limited Primary Cell Proliferation In Vitro yet Demonstrate Effective Host Integration In Vivo
by Benedetta Guagnini, Andrea Mazzoleni, Adrien Moya, Arnaud Scherberich, Barbara Medagli, Ivan Martin, Davide Porrelli, Manuele G. Muraro and Gianluca Turco
J. Funct. Biomater. 2025, 16(10), 386; https://doi.org/10.3390/jfb16100386 - 15 Oct 2025
Cited by 1 | Viewed by 1279
Abstract
Alginate-hydroxyapatite (AL) scaffolds modified with fibronectin (FN) or bioactive glass (BGMS10) have recently been characterized for their physicochemical properties and proposed as promising candidates for bone regeneration. Here, we present their first systematic biological evaluation, focusing on adhesion, proliferation, osteogenic differentiation, and in [...] Read more.
Alginate-hydroxyapatite (AL) scaffolds modified with fibronectin (FN) or bioactive glass (BGMS10) have recently been characterized for their physicochemical properties and proposed as promising candidates for bone regeneration. Here, we present their first systematic biological evaluation, focusing on adhesion, proliferation, osteogenic differentiation, and in vivo host response. We compared FN-, BG-, and unmodified AL scaffolds using an immortalized mesenchymal stromal cell line (M-SOD) and primary human bone marrow-derived (BM-MSCs) and adipose-derived stromal cells (ASCs). FN scaffolds enhanced initial adhesion across all cell types and supported proliferation in M-SODs, but primary BM-MSCs and ASCs showed minimal expansion, regardless of scaffold type. BG scaffolds promoted expression of late-stage osteogenic markers in BM-MSCs, consistent with their ion release profile, but had limited impact on ASCs. In vivo subcutaneous implantation of acellular scaffolds in nude mice revealed robust host cell infiltration and extracellular matrix deposition across all scaffold types, confirming biocompatibility and integration. However, vascularization remained limited and did not differ substantially between formulations. Together, these findings highlight a critical discrepancy between immortalized and primary stromal cell responses to scaffold cues, underscoring the choice of cell source when evaluating the biocompatibility of a novel scaffold. At the same time, the effective in vivo integration observed across scaffold types emphasizes the importance of host tissue responses for translational evaluation of functional biomaterials. Full article
(This article belongs to the Special Issue Bone Tissue Engineering: Recent Advances and Translation to Clinical Application)
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29 pages, 2552 KB  
Review
Acellular Extracellular Matrix Scaffolds in Regenerative Medicine: Advances in Decellularization and Clinical Applications
by Caijun Jin, Xinrui Zhang, Yongxun Jin, Pham Ngoc Chien and Chan Yeong Heo
J. Funct. Biomater. 2025, 16(10), 383; https://doi.org/10.3390/jfb16100383 - 12 Oct 2025
Cited by 9 | Viewed by 4400
Abstract
Decellularized extracellular matrix (dECM) scaffolds preserve native tissue structure and biochemical cues while minimizing immune responses, creating biomimetic templates that promote cell integration and tissue remodeling. This review examines the current state of dECM research, encompassing decellularization methods, scaffold quality evaluation assays, and [...] Read more.
Decellularized extracellular matrix (dECM) scaffolds preserve native tissue structure and biochemical cues while minimizing immune responses, creating biomimetic templates that promote cell integration and tissue remodeling. This review examines the current state of dECM research, encompassing decellularization methods, scaffold quality evaluation assays, and tissue-specific applications across dermis, nerve, heart, lung, adipose, and placental ECMs. We analyze commercially available dECM products and ongoing clinical trials, while highlighting recent advances including 3D bioprinting and the integration of dECM with stem cells and growth factors. Despite these promising developments, several challenges continue to limit broader clinical translation: protocol standardization, residual immunogenicity, mechanical durability, and regulatory, manufacturing, and cost barriers. To address these limitations, we outline future directions focusing on patient-specific scaffolds, scalable bioprocessing, and integrated biofabrication strategies that will enable the development of safe and effective dECM-based therapies. Full article
(This article belongs to the Special Issue Advanced Functional Biomaterials in Regenerative Medicine)
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30 pages, 2277 KB  
Review
Bioengineered In Situ-Forming Hydrogels as Smart Drug Delivery Systems for Postoperative Breast Cancer Immunotherapy: From Material Innovation to Clinical Translation
by Yan Yan, Yiling Chen, Litao Huang, Menghan Cai, Xia Yin, Yi Zhun Zhu and Li Ye
J. Funct. Biomater. 2025, 16(10), 381; https://doi.org/10.3390/jfb16100381 - 10 Oct 2025
Cited by 1 | Viewed by 3409
Abstract
Local recurrence after breast cancer surgery presents a critical challenge, demanding novel local immunotherapies capable of eliminating residual disease while avoiding systemic toxicity. In situ-forming hydrogels, functionalized with bioactive cargoes, represent a promising platform for precise spatiotemporal drug delivery directly into the post-resection [...] Read more.
Local recurrence after breast cancer surgery presents a critical challenge, demanding novel local immunotherapies capable of eliminating residual disease while avoiding systemic toxicity. In situ-forming hydrogels, functionalized with bioactive cargoes, represent a promising platform for precise spatiotemporal drug delivery directly into the post-resection tumor microenvironment. This review comprehensively examines the core design principles governing these advanced materials, highlighting their biocompatibility, stimuli-responsive behavior, tunable mechanics for conforming to surgical cavity, and capacity for multifunctional integration. A key mechanism discussed is how this controlled release profile orchestrates a temporal progression from innate immune activation to robust adaptive immunity. Despite significant promise, translational success faces substantial hurdles, including efficacy validation, scalable manufacturing, regulatory pathway definition, and the lack of predictive biomarkers. Future research priorities include optimizing drug/antigen release kinetics, establishing standardized characterization methods for complex biohybrid systems, and designing adaptive clinical trials incorporating detailed immunomonitoring. By integrating functional biomaterials with immuno-oncology, in situ-forming hydrogels offer a paradigm-shifting approach for postoperative cancer treatment. This review provides a strategic roadmap to accelerate their translation from bench to bedside. Full article
(This article belongs to the Special Issue Biomaterials for Drug Delivery and Cancer Therapy)
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26 pages, 5234 KB  
Article
Magnesium Ion-Mediated Regulation of Osteogenesis and Osteoclastogenesis in 2D Culture and 3D Collagen/Nano-Hydroxyapatite Scaffolds for Enhanced Bone Repair
by Sílvia Sá Paiva, Avelino Ferreira, Eavan Pakenham, Kulwinder Kaur, Brenton Cavanagh, Fergal J. O’Brien and Ciara M. Murphy
J. Funct. Biomater. 2025, 16(10), 363; https://doi.org/10.3390/jfb16100363 - 29 Sep 2025
Cited by 2 | Viewed by 1828
Abstract
Bone regeneration depends on a delicate balance between osteoblast-driven bone formation and osteoclast-mediated resorption, coordinated by complex biochemical cues. Magnesium (Mg2+) is known to modulate these processes. However, despite extensive research, its ability to simultaneously enhance osteogenesis and inhibit osteoclast activity [...] Read more.
Bone regeneration depends on a delicate balance between osteoblast-driven bone formation and osteoclast-mediated resorption, coordinated by complex biochemical cues. Magnesium (Mg2+) is known to modulate these processes. However, despite extensive research, its ability to simultaneously enhance osteogenesis and inhibit osteoclast activity remains unclear. In this study, we first investigated the effect of extracellular Mg2+ (0, 5, 10, 25, 50 mM) on osteoblast and osteoclast differentiation in 2D culture to determine whether a single Mg2+ dosing regimen can simultaneously promote osteogenesis while inhibiting osteoclast differentiation and maturation. A concentration dependent effect of Mg2+ was observed on both cell types, with increasing Mg2+ concentrations up to 25 mM significantly reducing osteoclast formation yet concurrently inhibiting osteogenic differentiation. At 50 mM, Mg2+ exhibited cytotoxic effects on both cell types. We then leveraged the osteogenic properties of biomimetic collagen/nano-hydroxyapatite (Coll/nHA) scaffolds by incorporating Mg2+ into the nHA phase to enable localised, controlled delivery. At a scaffold-loaded equivalent of 25 mM Mg2+, we observed enhanced bone matrix deposition alongside reduced osteoclast maturation, indicating a synergistic effect between Mg2+ and nHA in promoting osteogenesis. While no optimal synergistic dose was identified in 2D culture, these findings demonstrate that Coll-nHA scaffolds offer a promising strategy for localised Mg2+ delivery to enhance osteogenesis and suppress osteoclastogenesis. Importantly, the ease of scaffold modification opens the door to incorporating additional bioactive molecules, further advancing their potential in bone tissue engineering applications and the development of next-generation biomaterials for bone regeneration. Full article
(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)
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25 pages, 4563 KB  
Article
Metal Ion Release from PEO-Coated Ti6Al4V DMLS Alloy for Orthopedic Implants
by Shaghayegh Javadi, Laura Castro, Raúl Arrabal and Endzhe Matykina
J. Funct. Biomater. 2025, 16(10), 362; https://doi.org/10.3390/jfb16100362 - 28 Sep 2025
Cited by 1 | Viewed by 1145
Abstract
This study investigates the influence of plasma electrolytic oxidation (PEO) on corrosion resistance of Ti6Al4V alloys produced by direct metal laser sintering (DMLS) for orthopedic implants. PEO (300 s) and flash-PEO (60 s) coatings containing Si, Ca, P, Mg and Zn were applied [...] Read more.
This study investigates the influence of plasma electrolytic oxidation (PEO) on corrosion resistance of Ti6Al4V alloys produced by direct metal laser sintering (DMLS) for orthopedic implants. PEO (300 s) and flash-PEO (60 s) coatings containing Si, Ca, P, Mg and Zn were applied on both DMLS and wrought Ti6Al4V alloys. Samples, coated and uncoated, were characterized for microstructure, morphology and composition. Electrochemical behaviour was assessed by potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) in simulated body fluid (SBF) at 37 °C. Ion release was quantified by inductively coupled plasma optical emission spectroscopy (ICP-OES). DMLS alloy was more passive than wrought Ti6Al4V, releasing ~60% less Ti and ~25% less Al, but ~900% more V. For both alloys, correlation of corrosion current and ion release indicated that 98–99% of oxidized Ti remained in the passive layer. Flash-PEO produced uniform porous coatings composed of anatase and rutile with ~50% amorphous phase, while PEO yielded heterogeneous layers due to soft sparking. In both cases, coatings were the main source of ions. For the DMLS alloy, the best protection was afforded by flash-PEO, releasing 0.01 μg cm−2 d−1 Ti, 26 μg cm−2 d−1 Al, and 0.25 μg cm−2 d−1 V over 30 days. Full article
(This article belongs to the Special Issue Advances in Biomedical Alloys and Surface Modification)
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21 pages, 4703 KB  
Article
Development of Bioceramic Bone-Inspired Scaffolds Through Single-Step Melt-Extrusion 3D Printing for Segmental Defect Treatment
by Aikaterini Dedeloudi, Pietro Maria Bertelli, Laura Martinez-Marcos, Thomas Quinten, Imre Lengyel, Sune K. Andersen and Dimitrios A. Lamprou
J. Funct. Biomater. 2025, 16(10), 358; https://doi.org/10.3390/jfb16100358 - 23 Sep 2025
Viewed by 1552
Abstract
The increasing demand for novel tissue engineering (TE) applications in bone tissue regeneration underscores the importance of exploring advanced manufacturing techniques and biomaterials for personalised treatment approaches. Three-dimensional printing (3DP) technology facilitates the development of implantable devices with intricate geometries, enabling patient-specific therapeutic [...] Read more.
The increasing demand for novel tissue engineering (TE) applications in bone tissue regeneration underscores the importance of exploring advanced manufacturing techniques and biomaterials for personalised treatment approaches. Three-dimensional printing (3DP) technology facilitates the development of implantable devices with intricate geometries, enabling patient-specific therapeutic solutions. Although Fused Filament Fabrication (FFF) and Direct Ink Writing (DIW) are widely utilised for fabricating bone-like implants, the need for multiple processing steps often prolongs the overall production time. In this study, a single-step melt-extrusion 3DP technique was performed to develop multi-material scaffolds including bioceramics, hydroxyapatite (HA), and β-tricalcium phosphate (TCP) in both their bioactive and calcined forms at 10% and 20% w/w, within polycaprolactone (PCL) matrices. Printing parameters were optimised, and physicochemical properties of all biomaterials and final forms were evaluated. Thermal degradation and surface morphology analyses assessed the consistency and distribution of the ceramics across the different formulations. The tensile testing of the scaffolds defined the impact of each ceramic type and wt% on scaffold flexibility performance, while in vitro cell studies determined the cytocompatibility efficiency. Hence, all 3D-printed PCL–ceramic composite scaffolds achieved structural integrity and physicochemical and thermal stability. The mechanical profile of extruded samples was relevant to the ceramic consistency, providing valuable insights for further mechanotransduction investigations. Notably, all materials showed high cell viability and proliferation, indicating strong biocompatibility. Therefore, this additive manufacturing (AM) process is a precise and fast approach for developing biomaterial-based scaffolds, with potential applications in surgical restoration and support of segmental bone defects. Full article
(This article belongs to the Section Synthesis of Biomaterials via Advanced Technologies)
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31 pages, 2643 KB  
Review
Organ-Specific Strategies in Bioprinting: Addressing Translational Challenges in the Heart, Liver, Kidney, and Pancreas
by Mohamad Al Qassab, Moustafa Merheb, Safaa Sayadi, Pia Salloum, Zeina Dabbousi, Anthony Bayeh, Frederic Harb, Sami Azar and Hilda E. Ghadieh
J. Funct. Biomater. 2025, 16(10), 356; https://doi.org/10.3390/jfb16100356 - 23 Sep 2025
Cited by 3 | Viewed by 3480
Abstract
Organ bioprinting is a rapidly evolving field designed to address the persistent shortage of donor organs by engineering patient-specific tissues that replicate the function and structure of natural organs. Despite significant technological advancements, bioprinting still faces major obstacles, including tissue rejection, inadequate vascularization, [...] Read more.
Organ bioprinting is a rapidly evolving field designed to address the persistent shortage of donor organs by engineering patient-specific tissues that replicate the function and structure of natural organs. Despite significant technological advancements, bioprinting still faces major obstacles, including tissue rejection, inadequate vascularization, limited physiological functionality, and various ethical and translational challenges. In this review, we assess current bioprinting modalities, particularly extrusion-based printing, inkjet printing, laser-assisted bioprinting (LAB), and stereolithography/digital light processing (SLA/DLP), highlighting their individual strengths and limitations. We also explore different bioink formulations, focusing especially on hybrid bioinks as promising solutions to traditional bioink constraints. Additionally, this article thoroughly evaluates bioprinting strategies for four major organs: heart, liver, kidney, and pancreas. Each organ presents unique anatomical and physiological complexities, from cardiomyocyte immaturity and electromechanical mismatch in cardiac tissues to vascularization and zonation challenges in liver structures, intricate nephron patterning in kidney constructs, and immune rejection issues in pancreatic islet transplantation. Regulatory and ethical considerations critical for clinical translation are also addressed. By systematically analyzing these aspects, this review clarifies current gaps, emerging solutions, and future directions, providing a comprehensive perspective on advancing organ bioprinting toward clinical application. Full article
(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)
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36 pages, 2272 KB  
Review
Bio-Functional Nanomaterials for Enhanced Lung Cancer Therapy: The Synergistic Roles of Vitamins D and K
by Andreea Crintea, Camelia Munteanu, Tamás Ilyés, Ciprian N. Silaghi and Alexandra M. Crăciun
J. Funct. Biomater. 2025, 16(9), 352; https://doi.org/10.3390/jfb16090352 - 19 Sep 2025
Cited by 1 | Viewed by 1820
Abstract
Lung cancer remains a leading cause of cancer-related mortality worldwide, requiring the development of innovative and effective therapeutic strategies. Bio-functional nanomaterials, due to their unique physicochemical properties, offer a versatile platform for targeted drug delivery, controlled release, and multimodal therapies, thereby enhancing efficacy [...] Read more.
Lung cancer remains a leading cause of cancer-related mortality worldwide, requiring the development of innovative and effective therapeutic strategies. Bio-functional nanomaterials, due to their unique physicochemical properties, offer a versatile platform for targeted drug delivery, controlled release, and multimodal therapies, thereby enhancing efficacy and reducing the systemic toxicity of conventional treatments. Independently, both vitamin D and vitamin K have demonstrated significant anti-cancer properties, including inhibition of proliferation, induction of apoptosis, modulation of angiogenesis, and attenuation of metastatic potential in various cancer cell lines and in vivo models. However, their clinical application is often limited by poor bioavailability, rapid metabolism, and potential for off-target effects. Specifically, by enhancing the solubility, stability, and targeted accumulation of fat-soluble vitamins D and K within tumoral tissues for improved lung cancer therapy, this review emphasizes the novel and cooperative role of bio-functional nanomaterials in overcoming these limitations. Future studies should focus on the logical development of sophisticated nanomaterial carriers for optimal co-delivery plans and thorough in vivo validation, aiming to convert these encouraging preclinical results into successful clinical treatments for patients with lung cancer. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Biological Procedures of Biomaterials in Medical Applications (2nd Edition))
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18 pages, 540 KB  
Review
Bionanomaterials or Nanobiomaterials: Differences in Definitions and Applications
by Bogdan Walkowiak, Małgorzata Siatkowska and Piotr Komorowski
J. Funct. Biomater. 2025, 16(9), 351; https://doi.org/10.3390/jfb16090351 - 18 Sep 2025
Viewed by 2309
Abstract
Since the turn of the century, we have witnessed an extremely intensive development of biotechnology and nanotechnology, which, in terms of intensity can only be compared to the development of information technology and the resulting emergence of artificial intelligence. In the present review, [...] Read more.
Since the turn of the century, we have witnessed an extremely intensive development of biotechnology and nanotechnology, which, in terms of intensity can only be compared to the development of information technology and the resulting emergence of artificial intelligence. In the present review, we deliberately omit the development of information technology and artificial intelligence. Instead, our interest is focused on bionanomaterials and nanobiomaterials, their production and applications, and, in particular, the different meanings of these terms. We adopted an analysis of the literature published between January 2000 and May 2025, available in PubMed. The database was searched for selected areas: types (origin, structure, and function), manufacturing methods (chemical, physicochemical, and biological), and applications (medicine/pharmacy, textile technology, cosmetology, and agriculture/environment). Our findings revealed a significant increase in the number of publications for both terms, with nanobiomaterials predominating. The authors of the publications included in PubMed clearly outline the separation of meanings of both concepts, despite the lack of normative regulations in this regard. Nanoparticles are the most commonly represented type in the use of both terms, and drug delivery is a dominant application. However, it is worth noting the lack of nanobiomaterials in the agricultural/environmental application categories. Despite the enormous similarity between the terms “nanobiomaterials” and “bionanomaterials,” both in terms of nomenclature and application, there is a significant difference resulting from the manufacturing technologies and applications used. The term “nanobiomaterials” should be assigned only to biomaterials, in accordance with the definition of a biomaterial, regardless of their manufacturing technology, while the term “bionanomaterials” should be applied to all products of bionanotechnology, excluding products used as biomaterials. Full article
(This article belongs to the Special Issue Advanced Nanomaterials in Medicine: Innovations in Diagnostics, Therapy, and Regeneration)
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13 pages, 8569 KB  
Article
Comparative Evaluation of the Bone Regenerative Potential of a Novel Calcium Silicate-Modified Calcium Carbonate Graft Material: Histological and Micro-Computed Tomography Assessment Using a Rat Calvarial Defect Model
by Masataka Nakayama, Yu Kataoka, Naoki Kitamura, Chie Watanabe, Satoko Kujiraoka, Kikue Yamaguchi, Yuma Seki, Toshitake Furusawa, Hidero Unuma and Motohiro Munakata
J. Funct. Biomater. 2025, 16(9), 337; https://doi.org/10.3390/jfb16090337 - 9 Sep 2025
Viewed by 1338
Abstract
In the present study, we evaluated the usefulness of a porous sintered calcium carbonate body with CaSiO3 by comparing its osteogenic capacity with that of calcium carbonate without CaSiO3 and that of β-tricalcium phosphate (TP). A cranial defect model of eight-week-old [...] Read more.
In the present study, we evaluated the usefulness of a porous sintered calcium carbonate body with CaSiO3 by comparing its osteogenic capacity with that of calcium carbonate without CaSiO3 and that of β-tricalcium phosphate (TP). A cranial defect model of eight-week-old male Wistar rats was divided into three groups: calcium carbonate (CC), calcium carbonate-CaSiO3 composite (CC+CS), and TP. Micro-computed tomography (CT) and histological analysis were performed at four and eight weeks postoperatively. Upon quantitative evaluation of newly formed bone volume by radiography, the CC+CS group demonstrated the highest value at eight weeks postoperatively and exhibited significantly more new bone formations than the CC group (p < 0.05). Upon histological evaluation, the CC+CS group demonstrated significantly higher new bone formation than the CC group (p < 0.05). Furthermore, in terms of residual graft material ratio, at eight weeks postoperatively, the amount of residual graft material in the CC+CS group was significantly higher than that in the TP group (p < 0.05). Therefore, the addition of CaSiO3 enhances the functional regulation of calcium carbonate-based artificial bone and can be incorporated in bone graft materials. Full article
(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)
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17 pages, 3394 KB  
Article
Impact of 45S5-Bioactive Glass on Chondrocytes in Knee Osteoarthritis—In Vitro Study Exploring Cellular Responses
by Max Marinescu, Sébastien Hagmann, Jörg Fellenberg, Elena Tripel, Simone Gantz, Ravikumar Mayakrishnan, Aldo R. Boccaccini, Tobias Renkawitz, Babak Moradi, Fabian Westhauser and Hadrian Platzer
J. Funct. Biomater. 2025, 16(9), 339; https://doi.org/10.3390/jfb16090339 - 9 Sep 2025
Viewed by 1478
Abstract
Osteoarthritis (OA), the most common joint disease, is marked by cartilage degradation and chronic inflammation. While 45S5-bioactive glass (45S5-BG) is well-established in bone regeneration and has been suggested to exert immunomodulatory effects, its impact on OA chondrocytes remains largely unexplored. Therefore, this in [...] Read more.
Osteoarthritis (OA), the most common joint disease, is marked by cartilage degradation and chronic inflammation. While 45S5-bioactive glass (45S5-BG) is well-established in bone regeneration and has been suggested to exert immunomodulatory effects, its impact on OA chondrocytes remains largely unexplored. Therefore, this in vitro study investigated the effects of 45S5-BG microparticles (0.125 mg/mL) on chondrocytes derived from OA patients, evaluating its therapeutic potential in OA. Chondrocytes were cultured with or without 45S5-BG for 1 and 7 days. Gene expression of cartilage markers, cytokines, matrix metalloproteinases (MMPs), and toll-like receptors (TLRs) was analyzed by qPCR. Protein levels were assessed by ELISA. 45S5-BG stimulation significantly altered chondrocyte activity, inducing upregulation of IL-6, IL-1β, TNF-α, MMP-1/-3/-13, and TLR4. Expression of ACAN and COL2A1 was reduced, while COL10A1—a marker of chondrocyte hypertrophy—was significantly increased at day 1. These findings show a catabolic and pro-inflammatory shift in chondrocyte phenotype upon 45S5-BG exposure, showing no therapeutic benefit of 45S5-BG on OA chondrocytes. However, considering the pronounced effects on chondrocyte activity and the well-established bioactivity and biocompatibility of 45S5-BG, our findings suggest that modified BG formulations could be developed to enhance chondroprotective and anti-inflammatory properties, warranting further investigation in co-culture and in vivo models. Full article
(This article belongs to the Special Issue Bioactive Glass in Tissue Engineering Applications)
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29 pages, 2415 KB  
Review
Recent Advances in 3D Bioprinting of Porous Scaffolds for Tissue Engineering: A Narrative and Critical Review
by David Picado-Tejero, Laura Mendoza-Cerezo, Jesús M. Rodríguez-Rego, Juan P. Carrasco-Amador and Alfonso C. Marcos-Romero
J. Funct. Biomater. 2025, 16(9), 328; https://doi.org/10.3390/jfb16090328 - 4 Sep 2025
Cited by 9 | Viewed by 5829
Abstract
3D bioprinting has emerged as a key tool in tissue engineering by facilitating the creation of customized scaffolds with properties tailored to specific needs. Among the design parameters, porosity stands out as a determining factor, as it directly influences critical mechanical and biological [...] Read more.
3D bioprinting has emerged as a key tool in tissue engineering by facilitating the creation of customized scaffolds with properties tailored to specific needs. Among the design parameters, porosity stands out as a determining factor, as it directly influences critical mechanical and biological properties such as nutrient diffusion, cell adhesion and structural integrity. This review comprehensively analyses the state of the art in scaffold design, emphasizing how porosity-related parameters such as pore size, geometry, distribution and interconnectivity affect cellular behavior and mechanical performance. It also addresses advances in manufacturing methods, such as additive manufacturing and computer-aided design (CAD), which allow the development of scaffolds with hierarchical structures and controlled porosity. In addition, the use of computational modelling, in particular finite element analysis (FEA), as an essential predictive tool to optimize the design of scaffolds under physiological conditions is highlighted. This narrative review analyzed 112 core articles retrieved primarily from Scopus (2014–2025) to provide a comprehensive and up-to-date synthesis. Despite recent progress, significant challenges persist, including the lack of standardized methodologies for characterizing and comparing porosity parameters across different studies. This review identifies these gaps and suggests future research directions, such as the development of unified characterization and classification systems and the enhancement of nanoscale resolution in bioprinting technologies. By integrating structural design with biological functionality, this review underscores the transformative potential of porosity research applied to 3D bioprinting, positioning it as a key strategy to meet current clinical needs in tissue engineering. Full article
(This article belongs to the Special Issue Bio-Additive Manufacturing in Materials Science)
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19 pages, 3025 KB  
Article
Antibiofilm Activity of a Novel Calcium Phosphate Cement Doped with Two Antibiotics
by Eneko Elezgaray, Cassandra Pouget, Fanny Salmeron, Catherine Flacard, Jean-Philippe Lavigne, Vincent Cavaillès and Mikhael Bechelany
J. Funct. Biomater. 2025, 16(9), 320; https://doi.org/10.3390/jfb16090320 - 31 Aug 2025
Cited by 1 | Viewed by 1409
Abstract
This study presents the development of a degradable and biocompatible calcium phosphate cement (CPC) co-loaded with gentamicin (1.25 wt%) and vancomycin (4.25 wt%) for the local treatment of polymicrobial bone infections. The antibiotics were incorporated—individually or in combination—into the solid phase of Graftys [...] Read more.
This study presents the development of a degradable and biocompatible calcium phosphate cement (CPC) co-loaded with gentamicin (1.25 wt%) and vancomycin (4.25 wt%) for the local treatment of polymicrobial bone infections. The antibiotics were incorporated—individually or in combination—into the solid phase of Graftys® Quickset (GQS), an injectable CPC. Antibiotic loading modifies some of the intrinsic properties of the GQS cement. Porosity exceeded 53%, compressive strength reduced around 5 MPa, which is comparable to calcium sulphates cements, and the setting time, although extended, remained within the clinically acceptable threshold (<20 min), ensuring suitable handling. A burst release of both antibiotics was observed within the first 24 h, with sustained release over time and no cytotoxic effects on human osteoblasts. The dual-loaded cement exhibited broad-spectrum antibacterial activity against both Gram-positive and Gram-negative strains, including methicillin-resistant isolates, in both planktonic and biofilm forms. Notably, the combination of both antibiotics demonstrated superior efficacy compared to either antibiotic alone. These findings suggest that this dual-antibiotic-loaded CPC offers a promising strategy for localised treatment of complex bone infections such as osteomyelitis, where polymicrobial involvement and antibiotic resistance pose significant therapeutic challenges. Full article
(This article belongs to the Section Bone Biomaterials)
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30 pages, 2009 KB  
Review
Innovative Smart Materials in Restorative Dentistry
by Roxana Ionela Vasluianu, Livia Bobu, Iulian-Costin Lupu, Magda Antohe, Bogdan Petru Bulancea, Antonia Moldovanu, Ovidiu Stamatin, Catalina Cioloca Holban and Ana Maria Dima
J. Funct. Biomater. 2025, 16(9), 318; https://doi.org/10.3390/jfb16090318 - 30 Aug 2025
Cited by 2 | Viewed by 3094
Abstract
The growing challenge of biofilm-associated infections in dentistry necessitates advanced solutions. This review highlights the potential of smart bioactive and antibacterial materials—bioactive glass ceramics (BGCs), silver nanoparticle (AgNP)-doped polymers, and pH-responsive chitosan coatings—in transforming restorative dentistry. BGCs reduce biofilms by >90% while promoting [...] Read more.
The growing challenge of biofilm-associated infections in dentistry necessitates advanced solutions. This review highlights the potential of smart bioactive and antibacterial materials—bioactive glass ceramics (BGCs), silver nanoparticle (AgNP)-doped polymers, and pH-responsive chitosan coatings—in transforming restorative dentistry. BGCs reduce biofilms by >90% while promoting bone integration. AgNP-polymers effectively combat S. mutans and C. albicans but require controlled dosing (<0.3 wt% in PMMA) to avoid cytotoxicity. Chitosan coatings enable pH-triggered drug release, disrupting acidic biofilms. Emerging innovations like quaternary ammonium compounds, graphene oxide hybrids, and 4D-printed hydrogels offer on-demand antimicrobial and regenerative functions. However, clinical translation depends on addressing cytotoxicity, standardizing antibiofilm testing (≥3-log CFU/mL reduction), and ensuring long-term efficacy. These smart materials pave the way for self-defending restorations, merging infection control with tissue regeneration. Future advancements may integrate AI-driven design for multifunctional, immunomodulatory dental solutions. Full article
(This article belongs to the Special Issue Biomaterials in Dentistry: Current Status and Advances)
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25 pages, 3714 KB  
Review
Nature-Based Hydrogels Combined with Nanoparticles for Bone Regeneration
by Margarida Fernandes, Mónica Vieira, Daniela Peixoto and Natália M. Alves
J. Funct. Biomater. 2025, 16(9), 317; https://doi.org/10.3390/jfb16090317 - 30 Aug 2025
Cited by 4 | Viewed by 2622
Abstract
Bone is a calcified tissue composed of 60% inorganic compounds, 30% organic compounds, and 10% water. Bone exhibits an intrinsic regenerative capacity, enabling it to heal after fractures or adapt during growth. However, in cases of severe injury or extensive tissue loss, this [...] Read more.
Bone is a calcified tissue composed of 60% inorganic compounds, 30% organic compounds, and 10% water. Bone exhibits an intrinsic regenerative capacity, enabling it to heal after fractures or adapt during growth. However, in cases of severe injury or extensive tissue loss, this regenerative capacity becomes insufficient, often necessitating bone graft surgeries using autografts or allografts. Conventional grafting approaches present several limitations, driving the development of alternative strategies in tissue engineering. The system of hydrogel–nanoparticles (NPs) represents a new class of biomaterials designed to combine the advantages of both materials while mitigating their drawbacks. This review focuses on a combination of nature-based hydrogels with different types of nanoparticles and discusses their potential applications in bone regeneration. 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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16 pages, 5685 KB  
Article
Seeding of Dermal Substitutes with Glucose-Pretreated Nanofat Accelerates In Vivo Vascularization and Tissue Integration
by Valeria Pruzzo, Francesca Bonomi, Ettore Limido, Andrea Weinzierl, Yves Harder and Matthias W. Laschke
J. Funct. Biomater. 2025, 16(9), 311; https://doi.org/10.3390/jfb16090311 - 28 Aug 2025
Viewed by 1018
Abstract
The exposure of endothelial cells to high glucose concentrations promotes angiogenesis. The present study investigated whether this pro-angiogenic effect of glucose is suitable to improve the capability of nanofat to vascularize implanted dermal substitutes. Nanofat was processed from white adipose tissue originating from [...] Read more.
The exposure of endothelial cells to high glucose concentrations promotes angiogenesis. The present study investigated whether this pro-angiogenic effect of glucose is suitable to improve the capability of nanofat to vascularize implanted dermal substitutes. Nanofat was processed from white adipose tissue originating from green fluorescent protein (GFP)+ C57BL/6J donor mice and incubated for 1 h in Hank’s Balanced Salt Solution with or without (control) a high level of glucose (30 mM). The pretreated nanofat was seeded onto dermal substitutes, which were analyzed by intravital fluorescence microscopy, histology and immunohistochemistry in dorsal skinfold chambers of GFP− C57BL/6J mice to assess their vivo performance over a period of 14 days. A high level of glucose-pretreated nanofat did not induce a stronger immune response when compared to the control. However, it improved the vascularization of the implants, as shown by a significantly higher density of blood-perfused microvessels in the border zones (~3.6-fold increase) and more CD31+/GFP+ microvessels (~3-fold increase) inside the implants. Accordingly, high glucose-pretreated nanofat levels also enhanced the tissue integration of the dermal substitutes, as indicated by the deposition of more type I collagen (~2.9-fold increase). These findings suggest that the short-term exposure of nanofat to a high level of glucose represents a promising and clinically feasible strategy to enhance its regenerative properties when seeded onto dermal substitutes. Full article
(This article belongs to the Special Issue Advanced Functional Biomaterials in Regenerative Medicine)
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17 pages, 2755 KB  
Article
Enhanced Osteogenic Response to an Osteochondral Scaffold Modified with BMP-2 or Strontium-Enriched Amorphous Calcium Phosphate in a Co-Culture In Vitro Model
by Stefania Pagani, Manuela Salerno, Janis Locs, Jana Vecstaudza, Laura Dolcini, Milena Fini, Gianluca Giavaresi, Giuseppe Filardo and Marta Columbaro
J. Funct. Biomater. 2025, 16(8), 302; https://doi.org/10.3390/jfb16080302 - 21 Aug 2025
Cited by 3 | Viewed by 1633
Abstract
Background: A trilayered collagen/collagen–magnesium–hydroxyapatite (Col/Col-Mg-HA) scaffold is used in clinical practice to treat osteochondral lesions, but the regeneration of the subchondral bone is still not satisfactory. Objective: The aim of this study was to test, in vitro, the osteoinductivity induced by [...] Read more.
Background: A trilayered collagen/collagen–magnesium–hydroxyapatite (Col/Col-Mg-HA) scaffold is used in clinical practice to treat osteochondral lesions, but the regeneration of the subchondral bone is still not satisfactory. Objective: The aim of this study was to test, in vitro, the osteoinductivity induced by the addition of bone morphogenetic protein-2 (BMP-2) or amorphous calcium phosphate granules with strontium ions (Sr-ACP), in order to improve the clinical regeneration of subchondral bone, still incomplete. Methodology: Normal human osteoblasts (NHOsts) were seeded on the scaffolds and grown for 14 days in the presence of human osteoclasts and conditioned medium of human endothelial cells. NHOst adhesion and morphology were observed with transmission electron microscopy, and metabolic activity was tested by Alamar blue assay. The expression of osteoblast- and osteoclast-typical markers was evaluated by RT-PCR on scaffolds modified by enrichment with BPM-2 or Sr-ACP, as well as on unmodified material used as a control. Results: NHOsts adhered well to all types of scaffolds, maintained their typical morphology, and secreted abundant extracellular matrix. On the modified materials, COL1A1, SPARC, SPP1, and BGLAP were more expressed than on the unmodified ones, showing the highest expression in the presence of BMP-2. On Sr-ACP-enriched scaffolds, NHOsts had a lower proliferation rate and a lower expression of RUNX2, SP7, and ALPL compared to the other materials. The modified scaffolds, particularly the one containing Sr-ACP, increased the expression of the osteoclasts’ typical markers and decreased the OPG/RANKL ratio. Both types of scaffold modification were able to increase the osteoinductivity with respect to the original scaffold used in clinical practice. BMP-2 modification seemed to be more slightly oriented to sustain NHOst activity, and Sr-ACP seemed to be more slightly oriented to sustain the osteoclast activity. These could provide a concerted action toward better regeneration of the entire osteochondral unit. Full article
(This article belongs to the Special Issue Application of Biomaterials in Tissue Engineering and Regenerative Medicine)
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23 pages, 4373 KB  
Article
Effect of Zinc and Magnesium Compounds and Nano-Hydroxyapatite on the Physicochemical Properties and Biological Activity of Alginate and Gelatin Scaffolds for Osteochondral Defects
by Anna Morawska-Chochół, Agnieszka Urbaś, Witold Reczyński, Ewelina Kwiecień and Magdalena Rzewuska
J. Funct. Biomater. 2025, 16(8), 300; https://doi.org/10.3390/jfb16080300 - 19 Aug 2025
Viewed by 1376
Abstract
Composite scaffolds based on a hydrogel matrix modified with hydroxyapatite, magnesium, or zinc compounds are promising for filling and regenerating osteochondral defects due to the specific biological properties of these modifiers. The aim of this work was to evaluate the influence of hydroxyapatite, [...] Read more.
Composite scaffolds based on a hydrogel matrix modified with hydroxyapatite, magnesium, or zinc compounds are promising for filling and regenerating osteochondral defects due to the specific biological properties of these modifiers. The aim of this work was to evaluate the influence of hydroxyapatite, nano-hydroxyapatite, magnesium chloride, and zinc oxide on mechanical properties, swelling ability, behavior in a simulated biological environment (ion release, stability, bioactivity), and antibacterial effects. Furthermore, the influence of the hydrogel matrix (alginate, gelatin, alginate/gelatin) on the selected properties was also assessed. The results showed that the addition of ZnO improved the mechanical properties of all types of matrices most effectively. Additionally, zinc ions were gradually released into the environment and partially incorporated into the formed apatite. The released zinc ions increased the inhibition zones of Staphylococcus aureus growth; however, this effect was observed only in scaffolds with an alginate matrix. This indicates that hydrogel plays a key role in antibacterial effects, beyond the contribution of antibacterial additives. No effect of magnesium on bacterial growth inhibition was observed despite its rapid release. Magnesium ions promoted efficient secretion of apatite during incubation, although it was not stable. The addition of nano-HAP significantly increased the stability of the apatite precipitates. Full article
(This article belongs to the Special Issue Multifunctional Bio-Scaffolds for Cell Growth and Tissue Morphogenesis)
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22 pages, 1661 KB  
Article
Biliary Injuries Repair Using Copolymeric Scaffold: A Systematic Review and In Vivo Experimental Study
by Salvatore Buscemi, Giulia Bonventre, Andrea Gottardo, Mariano Licciardi, Fabio Salvatore Palumbo, Giovanni Cassata, Luca Cicero, Giulia Lo Monte, Roberto Puleio and Attilio Ignazio Lo Monte
J. Funct. Biomater. 2025, 16(8), 297; https://doi.org/10.3390/jfb16080297 - 18 Aug 2025
Viewed by 1117
Abstract
Background: Common bile duct (CBD) treatments are often associated with complications, limiting long-term efficacy. To overcome these issues, polymeric grafts have been suggested as promising alternatives, since they are highly customizable, biocompatible, and may reduce side effects frequency. Methods: A systematic review was [...] Read more.
Background: Common bile duct (CBD) treatments are often associated with complications, limiting long-term efficacy. To overcome these issues, polymeric grafts have been suggested as promising alternatives, since they are highly customizable, biocompatible, and may reduce side effects frequency. Methods: A systematic review was conducted, interrogating MEDLINE and Cochrane Library. Next, an in vivo study involved 20 pigs, which underwent a former controlled biliary injury. To repair the defect, a α,β-Poly(N-2-hydroxyethyl)-DL-Aspartamide (PHEA)–Polylactic-acid (PLA)–Polycaprolactone (PCL) scaffold was implanted. The animals were sacrificed at one and three months for gross and histological examinations, to assess tissue integration and healing outcomes. Results: The systematic review highlighted that such scaffolds have shown promising results in CBD regeneration, both in single and joined applications. These findings were confirmed by the in vivo study, where the use of such scaffolds—particularly, the planar ones—led to safe and complete bile duct regeneration. Histological analysis revealed lymphomonocytic infiltrates and neovascularization, while microscopic examination showed progressive scaffold degradation accompanied by biliary tissue regeneration. Conclusions: Experimental results are consistent with the literature, confirming the potential of such polymeric scaffolds in aiding complete CBD regeneration and being reabsorbed shortly after. Still, further studies are needed to fully validate their translational application. PROSPERO ID: CRD420251115056. Full article
(This article belongs to the Special Issue Polymers Materials Used in Biomedical Engineering)
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32 pages, 2710 KB  
Review
Polyphosphazene-Based Nanotherapeutics
by Sara Gutierrez-Gutierrez, Rocio Mellid-Carballal, Noemi Csaba and Marcos Garcia-Fuentes
J. Funct. Biomater. 2025, 16(8), 285; https://doi.org/10.3390/jfb16080285 - 2 Aug 2025
Cited by 1 | Viewed by 2497
Abstract
Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide [...] Read more.
Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide spectrum of functional properties, including the formation of multifunctional nanostructures tailored for specific therapeutic needs. These attributes enable PPZs to address several critical challenges associated with conventional drug delivery systems, such as poor pharmacokinetics and pharmacodynamics. By modulating solubility profiles, enhancing drug stability, enabling targeted delivery, and supporting controlled release, PPZs offer a robust platform for improving therapeutic efficacy and patient outcomes. This review explores the fundamental chemistry, biopharmaceutical characteristics, and biomedical applications of PPZs, particularly emphasizing their role in zero-dimensional nanotherapeutic systems, including various nanoparticle formulations. PPZ-based nanotherapeutics are further examined based on their drug-loading mechanisms, which include electrostatic complexation in polyelectrolytic systems, self-assembly in amphiphilic constructs, and covalent conjugation with active pharmaceutical agents. Together, these strategies underscore the potential of PPZs as a next-generation material for advanced drug delivery platforms. Full article
(This article belongs to the Special Issue Nanomaterials for Drug Targeting and Drug Delivery (2nd Edition))
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16 pages, 1867 KB  
Review
Histological Processing of Scaffolds: Challenges and Solutions
by Tomas Ragauskas, Ilona Uzieliene and Eiva Bernotiene
J. Funct. Biomater. 2025, 16(8), 279; https://doi.org/10.3390/jfb16080279 - 31 Jul 2025
Cited by 1 | Viewed by 3924
Abstract
Scaffolds are widely used in bioengineering, both as 3D native tissue-mimicking models for investigating mechanisms under physiological and pathological conditions and also as implantable agents in regenerative medicine. Histological approaches, mainly formalin-fixed paraffin-embedded (FFPE) and frozen sample sectioning, are commonly applied to evaluate [...] Read more.
Scaffolds are widely used in bioengineering, both as 3D native tissue-mimicking models for investigating mechanisms under physiological and pathological conditions and also as implantable agents in regenerative medicine. Histological approaches, mainly formalin-fixed paraffin-embedded (FFPE) and frozen sample sectioning, are commonly applied to evaluate cell distribution and tissue-like properties of scaffolds. However, standard histological processing is not always compatible with the materials that scaffolds are made of. Thus, some adaptations to protocols are required to obtain intact sections. In this review we discuss challenges related to the histological processing of scaffolds and solutions to overcome them. We sequentially cover processing steps of the three main histological techniques for sample preparation—cryomicrotomy, FFPE samples microtomy and vibrating microtomy. Furthermore, we highlight the critical considerations in choosing the most appropriate method based on scaffold composition, mechanical properties and the specific research question. The goal of this review is to provide practical guidance on choosing reliable histological evaluation of complex scaffold-based systems in tissue engineering research. Full article
(This article belongs to the Special Issue Biomaterials: Functionalization, Diagnostics, and Modeling for Advanced Therapeutic and Regenerative Applications)
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13 pages, 2153 KB  
Article
Interaction of MG63 Human Osteosarcoma-Derived Cells on S53P4 Bioactive Glass: An In Vitro Study
by Valentin Schmidt, Beáta Polgár, Vanda Ágnes Nemes, Tímea Dergez, László Janovák, Péter Maróti, Szilárd Rendeki, Kinga Turzó and Balázs Patczai
J. Funct. Biomater. 2025, 16(8), 275; https://doi.org/10.3390/jfb16080275 - 29 Jul 2025
Viewed by 1892
Abstract
Bioactive glass materials have been used for decades in orthopedic surgery, traumatology, and oral and maxillofacial surgery to repair bone defects. This study aimed to evaluate in vitro the survival and proliferation of MG63 human osteosarcoma-derived cells on S53P4 bioactive glass (BonAlive® [...] Read more.
Bioactive glass materials have been used for decades in orthopedic surgery, traumatology, and oral and maxillofacial surgery to repair bone defects. This study aimed to evaluate in vitro the survival and proliferation of MG63 human osteosarcoma-derived cells on S53P4 bioactive glass (BonAlive® granules). Microscopic visualization was performed to directly observe the interactions between the cells and the material. Osteoblast-like cells were examined on non-adherent test plates, on tissue culture (TC)-treated plates and on the surface of the bioglass to assess the differences. Cell survival and proliferation were monitored using a CCK-8 optical density assay. Comparing the mean OD of MG63 cells in MEM on TC-treated plates with cells on BG, we detected a significant difference (p < 0.05), over each time of observation. The sustained cell proliferation confirmed the non-cytotoxic property of the bioglass, as the cell number increased continuously at 48, 72, 96, and 168 h and even did not plateau after 168 h. Since the properties of bioglasses can vary significantly depending on their composition and environment, a thorough characterization of their biocompatibility is crucial to ensure their effective and appropriate application—for example, during hip and knee prosthesis insertion. Full article
(This article belongs to the Section Bone Biomaterials)
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14 pages, 1487 KB  
Article
On the Interplay Between Roughness and Elastic Modulus at the Nanoscale: A Methodology Study with Bone as Model Material
by Alessandro Gambardella, Gregorio Marchiori, Melania Maglio, Marco Boi, Matteo Montesissa, Jessika Bertacchini, Stefano Biressi, Nicola Baldini, Gianluca Giavaresi and Marco Bontempi
J. Funct. Biomater. 2025, 16(8), 276; https://doi.org/10.3390/jfb16080276 - 29 Jul 2025
Cited by 1 | Viewed by 1307
Abstract
Atomic force microscopy (AFM)-based nanoindentation enables investigation of the mechanical response of biological materials at a subcellular scale. However, quantitative estimates of mechanical parameters such as the elastic modulus (E) remain unreliable because the influence of sample roughness on E measurements at the [...] Read more.
Atomic force microscopy (AFM)-based nanoindentation enables investigation of the mechanical response of biological materials at a subcellular scale. However, quantitative estimates of mechanical parameters such as the elastic modulus (E) remain unreliable because the influence of sample roughness on E measurements at the nanoscale is still poorly understood. This study re-examines the interpretation of roughness from a more rigorous perspective and validates an experimental methodology to extract roughness at each nanoindentation site—i.e., the local roughness γs—with which the corresponding E value can be accurately correlated. Cortical regions of a murine tibia cross-section, characterized by complex nanoscale morphology, were selected as a testbed. Eighty non-overlapping nanoindentations were performed using two different AFM tips, maintaining a maximum penetration depth of 10 nm for each measurement. Our results show a slight decreasing trend of E versus γs (Spearman’s rank correlation coefficient ρ = −0.27187). A total of 90% of the E values are reliable when γs < 10 nm (coefficient of determination R2 > 0.90), although low γs values are associated with significant dispersion around E (γs = 0) = E0 = 1.18 GPa, with variations exceeding 50%. These findings are consistent with a qualitative tip-to-sample contact model that accounts for the pronounced roughness heterogeneity typical of bone topography at the nanoscale. Full article
(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)
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27 pages, 6405 KB  
Article
PDMS Membranes Drilled by Proton Microbeam Writing: A Customizable Platform for the Investigation of Endothelial Cell–Substrate Interactions in Transwell-like Devices
by Vita Guarino, Giovanna Vasco, Valentina Arima, Rosella Cataldo, Alessandra Zizzari, Elisabetta Perrone, Giuseppe Gigli and Maura Cesaria
J. Funct. Biomater. 2025, 16(8), 274; https://doi.org/10.3390/jfb16080274 - 28 Jul 2025
Viewed by 2922
Abstract
Cell migration assays provide valuable insights into pathological conditions, such as tumor metastasis and immune cell infiltration, and the regenerative capacity of tissues. In vitro tools commonly used for cell migration studies exploit commercial transwell systems, whose functionalities can be improved through engineering [...] Read more.
Cell migration assays provide valuable insights into pathological conditions, such as tumor metastasis and immune cell infiltration, and the regenerative capacity of tissues. In vitro tools commonly used for cell migration studies exploit commercial transwell systems, whose functionalities can be improved through engineering of the pore pattern. In this context, we propose the fabrication of a transwell-like device pursued by combining the proton beam writing (PBW) technique with wet etching onto thin layers of polydimethylsiloxane (PDMS). The resulting transwell-like device incorporates a PDMS membrane with finely controllable pore patterning that was used to study the arrangement and migration behavior of HCMEC/D3 cells, a well-established human brain microvascular endothelial cell model widely used to study vascular maturation in the brain. A comparison between commercial polycarbonate membranes and the PBW-holed membranes highlights the impact of the ordering of the pattern and porosity on cellular growth, self-organization, and transmigration by combining fluorescent microscopy and advanced digital processing. Endothelial cells were found to exhibit distinctive clustering, alignment, and migratory behavior close to the pores of the designed PBW-holed membrane. This is indicative of activation patterns associated with cytoskeletal remodeling, a critical element in the angiogenic process. This study stands up as a novel approach toward the development of more biomimetic barrier models (such as organ-on-chips). Full article
(This article belongs to the Collection Feature Papers in Biomaterials for Healthcare Applications)
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24 pages, 5956 KB  
Article
Effects of Different Surface Treatments and Accelerated Aging on Dental Zirconia—An In Vitro Study
by Mihaela Pantea, Lucian Toma Ciocan, Vlad Gabriel Vasilescu, Georgeta Voicu, Adrian-Ionut Nicoară, Florin Miculescu, Robert Ciocoiu, Ana Maria Cristina Țâncu, Elena Georgiana Banu and Marina Imre
J. Funct. Biomater. 2025, 16(7), 263; https://doi.org/10.3390/jfb16070263 - 16 Jul 2025
Cited by 2 | Viewed by 1950
Abstract
This in vitro study aimed to compare the effects of various surface treatments and hydrothermal aging on the phase composition, microstructure, and compressive strength of dental zirconia (ZrO2). Forty-eight zirconia cubes (8 × 8 × 8 mm) were fabricated using CAD/CAM [...] Read more.
This in vitro study aimed to compare the effects of various surface treatments and hydrothermal aging on the phase composition, microstructure, and compressive strength of dental zirconia (ZrO2). Forty-eight zirconia cubes (8 × 8 × 8 mm) were fabricated using CAD/CAM from two materials: infrastructure zirconia (Group S1) and super-translucent multilayered monolithic zirconia (Group S2). Four samples of each material were analyzed in their pre-sintered state (S1-0, S2-0). The remaining specimens were sintered and assigned to sub-groups based on surface treatment: untreated, sandblasted with 30 µm or 50 µm Al2O3, polished, or polished and glazed. Characterization was performed using EDX, SEM, XRD with Rietveld refinement, Raman spectroscopy, and compressive testing before and after accelerated hydrothermal aging, according to EN ISO 13356:2015. EDX revealed a higher yttria content in monolithic zirconia (10.57 wt%) than in infrastructure zirconia (6.51 wt%). SEM images showed minimal changes in polished samples but clear surface damage after sandblasting, which was more pronounced with larger abrasive particles. XRD and Raman confirmed that sandblasting promoted the tetragonal (t-ZrO2) to monoclinic (m-ZrO2) phase transformation (t→m), amplified further by hydrothermal aging. The polished groups showed greater phase stability post-aging. Compressive strength decreased in all treated and aged samples, with monolithic zirconia being more affected. Polished samples displayed the best surface quality and structural resilience across both materials. These findings underline the impact of clinical surface treatments on zirconia’s long-term mechanical and structural behavior. Full article
(This article belongs to the Special Issue New Trends in Biomaterials and Implants for Dentistry (2nd Edition))
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22 pages, 8601 KB  
Article
Synthesis of Ag2O/Ag Nanoparticles Using Puerarin: Characterization, Cytotoxicity, In Ovo Safety Profile, Antioxidant, and Antimicrobial Potential Against Nosocomial Pathogens
by Sergio Liga, Raluca Vodă, Lavinia Lupa, Elena-Alina Moacă, Delia Muntean, Lucian Barbu-Tudoran, Maria Suciu, Vlad Socoliuc and Francisc Péter
J. Funct. Biomater. 2025, 16(7), 258; https://doi.org/10.3390/jfb16070258 - 11 Jul 2025
Cited by 5 | Viewed by 2541
Abstract
(1) Background: Our study investigates the green synthesis of Ag2O/Ag nanoparticles using the isoflavone Puerarin as a bioreductor. (2) Methods: The PUE@Ag2O/Ag nanoparticles were characterized using various techniques, including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), electronic [...] Read more.
(1) Background: Our study investigates the green synthesis of Ag2O/Ag nanoparticles using the isoflavone Puerarin as a bioreductor. (2) Methods: The PUE@Ag2O/Ag nanoparticles were characterized using various techniques, including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), electronic microscopy (TEM, SEM), energy dispersive X-ray spectroscopy (EDX), and dynamic light scattering (DLS). Biological activities were assessed through antimicrobial testing, cytotoxicity assays on human keratinocytes and melanoma cells, and an in ovo screening using the HET-CAM assay. (3) Results: The formation of crystalline Ag2O/Ag nanoparticles with sizes below 100 nm was accomplished with Puerarin. Despite their high cytotoxicity at all tested concentrations, the nanoparticles showed antioxidant activity with IC50 981.5 ± 94.2 μg/mL, antibacterial activity against several clinically relevant nosocomial strains (Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa), and no local irritant effects or inhibition of angiogenesis in the HET-CAM assay. (4) Conclusions: This study provides insights into the synthesis, characterization, and biological profile of PUE@Ag2O/Ag nanoparticles for potential biomedical applications. Full article
(This article belongs to the Special Issue Nanoparticles and Nanomaterials to Counteract Healthcare-Associated Infections)
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19 pages, 1935 KB  
Article
Mechanical Properties and Functional Assessment of PMMA Bone Cements Modified with Glassy Carbon
by Robert Karpiński and Jakub Szabelski
J. Funct. Biomater. 2025, 16(7), 254; https://doi.org/10.3390/jfb16070254 - 9 Jul 2025
Cited by 5 | Viewed by 3293
Abstract
Poly(methyl methacrylate) (PMMA)-based bone cements are widely used in orthopaedic surgery, yet their inherent brittleness, lack of bioactivity, and exothermic polymerization remain critical limitations. Recent strategies have focused on modifying PMMA with functional additives to improve not only mechanical performance but also thermal [...] Read more.
Poly(methyl methacrylate) (PMMA)-based bone cements are widely used in orthopaedic surgery, yet their inherent brittleness, lack of bioactivity, and exothermic polymerization remain critical limitations. Recent strategies have focused on modifying PMMA with functional additives to improve not only mechanical performance but also thermal behaviour and biological interactions. This study investigates the mechanical properties of two commercial PMMA cements—Palamed® (antibiotic-free) and Refobacin Plus G (gentamicin-loaded)—reinforced with glassy carbon (GC) particles of two different grain sizes (0.4–1.2 µm and 20–50 µm) and various concentrations. The results demonstrate that coarse GC particles (20–50 µm) significantly reduced compressive strength, particularly in the antibiotic-loaded cement. In contrast, the incorporation of fine GC particles (0.4–1.2 µm) did not markedly impair mechanical performance in Palamed®, suggesting better compatibility with the PMMA matrix. In addition to mechanical enhancement, the structural and chemical stability of glassy carbon may contribute to improved biological response and reduced polymerization heat. These findings highlight the potential of glassy carbon as a functional additive for designing PMMA-based biomaterials that combine improved mechanical properties with favourable characteristics for long-term implant integration. Full article
(This article belongs to the Special Issue State of the Art: Biomaterials in Bone Implant and Regeneration)
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16 pages, 1856 KB  
Article
Biomimetic Hydrogels for In Vitro Modelling of Nucleus Pulposus Degeneration: Effects of Extracellular Matrix Compositional Change on Physicochemical Properties and Cell Phenotype
by Narjes Rashidi, Nicholas Dowell, Derek Covill, John Shepperd and Matteo Santin
J. Funct. Biomater. 2025, 16(7), 253; https://doi.org/10.3390/jfb16070253 - 8 Jul 2025
Cited by 1 | Viewed by 5096
Abstract
The intervertebral disc, an anatomical compartment interposed between vertebral bodies, plays a key role in spine flexibility and compression loading. It comprises three tissues: the nucleus pulposus, the annulus fibrosus, and the end plates. Degeneration-related changes in the extracellular matrix of the nucleus [...] Read more.
The intervertebral disc, an anatomical compartment interposed between vertebral bodies, plays a key role in spine flexibility and compression loading. It comprises three tissues: the nucleus pulposus, the annulus fibrosus, and the end plates. Degeneration-related changes in the extracellular matrix of the nucleus pulposus upon ageing or pathological conditions prompted the present investigation into the impact of proteoglycan reduction, the main constituent of the healthy nucleus pulposus, on its physicochemical properties and cellular phenotypical changes. To mimic the native extracellular matrix, three-dimensional NP-mimicking constructs were developed using a biomimetic hydrogel composed of collagen type I, collagen type II, and proteoglycans. This system was fabricated using a bottom-up approach, employing highly pure monomeric collagen types I and II, which were induced to form a reconstituted fibrillar structure closely resembling the natural NP microenvironment. A comprehensive physicochemical characterization was conducted at varying proteoglycan percentages using scanning electron microscopy (SEM), FTIR, rheological tests, and water retention property analysis. The effect of microenvironment changes on the phenotype of nucleus pulposus cells was studied by their encapsulation within the various collagen–proteoglycan hydrogels. The morphological and immunochemistry analysis of the cells was performed to study the cell–matrix adhesion pathways and the expression of the cellular regulator hypoxia-inducible factor 1 alpha. These were linked to the analysis of the synthesis of healthy or pathological extracellular matrix components. The findings reveal that the reduction in proteoglycan content in the nucleus pulposus tissue triggers a pathological pathway, impairing the rheological and water retention properties. Consequently, the cell phenotypes are altered, inducing the synthesis of collagen type I rather than securing the natural physiological remodelling process by the synthesis of collagen type II and proteoglycans. Identifying the proteoglycan content threshold that triggers these pathological phenotypical changes could provide new diagnostic markers and early therapeutic strategies for intervertebral disc degeneration. Full article
(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)
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42 pages, 1721 KB  
Review
Electrospinning Enables Opportunity for Green and Effective Antibacterial Coatings of Medical Devices
by Saverio Caporalini, Bahareh Azimi, Samir Zergat, Mahdi Ansari Chaharsoughi, Homa Maleki, Giovanna Batoni and Serena Danti
J. Funct. Biomater. 2025, 16(7), 249; https://doi.org/10.3390/jfb16070249 - 6 Jul 2025
Cited by 7 | Viewed by 3663
Abstract
The growing antimicrobial resistance and the increasing environmental concerns associated with conventional antibacterial agents have prompted a search for more effective and sustainable alternatives. Biopolymer-based nanofibers are promising candidates to produce environment-friendly antibacterial coatings, owing to their high surface-to-volume ratio, structural adaptability, and [...] Read more.
The growing antimicrobial resistance and the increasing environmental concerns associated with conventional antibacterial agents have prompted a search for more effective and sustainable alternatives. Biopolymer-based nanofibers are promising candidates to produce environment-friendly antibacterial coatings, owing to their high surface-to-volume ratio, structural adaptability, and tunable porosity. These features make them particularly well-suited for delivering antimicrobial agents in a controlled manner and for physically modifying the surface of medical devices. This review critically explores recent advances in the use of electrospun fibers enhanced with natural antimicrobial agents as eco-friendly surface coatings. The mechanisms of antibacterial action, key factors affecting their efficacy, and comparisons with conventional antibacterial agents are discussed herein. Emphasis is placed on the role of a “green electrospinning” process, which utilizes bio-based materials and nontoxic solvents, to enable coatings able to better combat antibiotic-resistant pathogens. Applications in various clinical settings, including implants, wound dressings, surgical textiles, and urinary devices, are explored. Finally, the environmental benefits and prospects for the scalability and sustainability of green coatings are discussed to underscore their relevance to next-generation, sustainable solutions in healthcare. Full article
(This article belongs to the Special Issue Advanced Technologies for Processing Functional Biomaterials)
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44 pages, 2343 KB  
Review
Head and Neck 3D Bioprinting—A Review on Recent Advancements in Soft Tissue 3D Bioprinting and Medical Applications
by Iosif-Aliodor Timofticiuc, Ana Caruntu, Christiana Diana Maria Dragosloveanu, Andreea-Elena Scheau, Ioana Anca Badarau, Argyrios Periferakis, Serban Dragosloveanu, Andreea Cristiana Didilescu, Constantin Caruntu and Cristian Scheau
J. Funct. Biomater. 2025, 16(7), 240; https://doi.org/10.3390/jfb16070240 - 30 Jun 2025
Cited by 5 | Viewed by 6742
Abstract
Recent developments in 3D bioprinting offer innovative alternative solutions to classical treatments for head and neck defects. Soft tissues in an anatomical area as diverse in composition as the head and neck are complex in terms of structure and function. Understanding how cellular [...] Read more.
Recent developments in 3D bioprinting offer innovative alternative solutions to classical treatments for head and neck defects. Soft tissues in an anatomical area as diverse in composition as the head and neck are complex in terms of structure and function. Understanding how cellular interaction underlies functionality has led to the development of bioinks capable of mimicking the natural morphology and roles of different human parts. Moreover, from the multitude of recently developed materials, there are now many options for building scaffolds that potentiate the activity of these cells. The fidelity and accuracy of the utilized techniques ensure maximum precision in terms of model construction. Emerging technologies will allow for improved control of the scaffold, facilitating optimal results in the treatment of various pathologies, without concerns about the availability of donors, immunological response, or any other side effects that traditional treatments withhold. This paper explores the current landscape of bioprinted scaffolds and their applications in the head and neck region, with a focus on the properties and use of natural and synthetic bioinks in the attempt to replicate the biomechanical features of native tissues. Customization capabilities that support anatomical precision and biofunctionality are also addressed. Moreover, regulatory requirements, as well as current challenges related to biocompatibility, immune response, and vascularization, are critically discussed in order to provide a comprehensive overview of the pathway to clinical application. Full article
(This article belongs to the Special Issue The 15th Anniversary of JFB—Functional Biomaterials: Bioactive Properties and Medical Applications)
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14 pages, 2179 KB  
Article
One-Pot Anodic Electrodeposition of Dual-Cation-Crosslinked Sodium Alginate/Carboxymethyl Chitosan Interpenetrating Hydrogel with Vessel-Mimetic Heterostructures
by Xuli Li, Yuqing Qu, Yong Zhang, Pei Chen, Siyu Ding, Miaomiao Nie, Kun Yan and Shefeng Li
J. Funct. Biomater. 2025, 16(7), 235; https://doi.org/10.3390/jfb16070235 - 26 Jun 2025
Viewed by 1446
Abstract
This study develops a one-pot anodic templating electrodeposition strategy using dual-cation-crosslinking and interpenetrating networks, coupled with pulsed electrical signals, to fabricate a vessel-mimetic multilayered tubular hydrogel. Typically, the anodic electrodeposition is performed in a mixture of sodium alginate (SA) and carboxymethyl chitosan (CMC), [...] Read more.
This study develops a one-pot anodic templating electrodeposition strategy using dual-cation-crosslinking and interpenetrating networks, coupled with pulsed electrical signals, to fabricate a vessel-mimetic multilayered tubular hydrogel. Typically, the anodic electrodeposition is performed in a mixture of sodium alginate (SA) and carboxymethyl chitosan (CMC), with the ethylenediaminetetraacetic acid calcium disodium salt hydrate (EDTA·Na2Ca) incorporated to provide a secondary ionic crosslinker (i.e., Ca2+) and modulate the cascade reaction diffusion process. The copper wire electrodes serve as templates for electrochemical oxidation and enable a copper ion (i.e., Cu2+)-induced tubular hydrogel coating formation, while pulsed electric fields regulate layer-by-layer deposition. The dual-cation-crosslinked interpenetrating hydrogels (CMC/SA-Cu/Ca) exhibit rapid growth rates and tailored mechanical strength, along with excellent antibacterial performance. By integrating the unique pulsed electro-fabrication with biomimetic self-assembly, this study addresses challenges in vessel-mimicking structural complexity and mechanical compatibility. The approach enables scalable production of customizable multilayered hydrogels for artificial vessel grafts, smart wound dressings, and bioengineered organ interfaces, demonstrating broad biomedical potential. Full article
(This article belongs to the Special Issue Advances in Multifunctional Hydrogels for Biomedical Application (2nd Edition))
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25 pages, 3895 KB  
Review
The Biomedical Limitations of Magnetic Nanoparticles and a Biocompatible Alternative in the Form of Magnetotactic Bacteria
by Natalia L. Paul, Rahela Carpa, Rodica Elena Ionescu and Catalin Ovidiu Popa
J. Funct. Biomater. 2025, 16(7), 231; https://doi.org/10.3390/jfb16070231 - 23 Jun 2025
Cited by 3 | Viewed by 2703
Abstract
Nanotechnology has an increasing impact and a great potential in various biological and medical applications. Magnetic nanoparticles (MNPs) stand out for their unique properties, a reason why they have a varied spectrum of applicability in different sectors of activity; in this paper we [...] Read more.
Nanotechnology has an increasing impact and a great potential in various biological and medical applications. Magnetic nanoparticles (MNPs) stand out for their unique properties, a reason why they have a varied spectrum of applicability in different sectors of activity; in this paper we focus on the medical field. Magnetotactic bacteria (MTB) are a group of Gram-negative prokaryotes that migrate in one direction or another under the influence of an external magnetic field and are a category of microorganisms that constitutively perform the biomineralization of magnetic nanoparticles in the cytoplasm. This review focuses on the general and particular characteristics of magnetotactic bacteria in close correlation with their utility in the medical field, starting with the medical applications of magnetic nanoparticles and arriving at the potential role in nanomedicine of MNPs extracted from MTB. Full article
(This article belongs to the Special Issue Biomaterials: Functionalization, Diagnostics, and Modeling for Advanced Therapeutic and Regenerative Applications)
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