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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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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
Viewed by 785
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 835
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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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 825
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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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 682
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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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 2 | Viewed by 2089
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
Viewed by 816
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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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
Viewed by 1317
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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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
Viewed by 1575
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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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 653
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 1 | Viewed by 1057
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 803
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 704
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
Viewed by 1411
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
Viewed by 1404
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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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
Viewed by 902
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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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 1172
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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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 2122
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 1082
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 1 | Viewed by 1508
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
Viewed by 2007
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
Viewed by 3560
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 1 | Viewed by 2088
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 2 | Viewed by 4567
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 1007
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 2 | Viewed by 1609
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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24 pages, 7602 KB  
Article
Developing Bioengineered 3D-Printed Composite Scaffolds with Antimicrobial Potential for Bone Tissue Regeneration
by Andreea Trifan, Eduard Liciu, Cristina Busuioc, Izabela-Cristina Stancu, Adela Banciu, Carmen Nicolae, Mihai Dragomir, Doru-Daniel Cristea, Rosina-Elena Sabău, David-Andrei Nițulescu and Alexandru Paraschiv
J. Funct. Biomater. 2025, 16(6), 227; https://doi.org/10.3390/jfb16060227 - 19 Jun 2025
Cited by 1 | Viewed by 1356
Abstract
This research activity proposes to produce composite hydrogel–bioactive glass. The primary purpose of this research is to develop and optimize 3D-printed scaffolds using doped bioglass, aimed at enhancing bone regeneration in bone defects. The bioglass, a bioactive material known for its bone-bonding ability [...] Read more.
This research activity proposes to produce composite hydrogel–bioactive glass. The primary purpose of this research is to develop and optimize 3D-printed scaffolds using doped bioglass, aimed at enhancing bone regeneration in bone defects. The bioglass, a bioactive material known for its bone-bonding ability (SiO2–P2O5–CaO–Na2O), co-doped with europium and silver was synthesized and doped to improve its biological properties. This doped bioglass was then combined with a biocompatible hydrogel, chosen for its adequate cellular response and printability. The composite material was printed to form a scaffold, providing a structure that not only supports the damaged bone but also encourages osteogenesis. A variety of methods were employed to assess the rheological, compositional, and morphological characteristics of the samples: Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDS). Additionally, simulated body fluid (SBF) immersion for bioactivity monitoring and immunocytochemistry for cell viability were used to evaluate the biological response of the scaffolds. Full article
(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)
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16 pages, 1024 KB  
Systematic Review
Potential Applications of PRP-Enhanced Polybutylene Succinate Graft as Vascular Access for Chemotherapy in Oncological Patients: A Systematic Review
by Andrea Gottardo, Giulia Bonventre, Tancredi Didier Bazan Russo, Pietro Zanatta, Giulia Lo Monte, Valerio Gristina, Antonio Galvano, Antonio Russo and Attilio Ignazio Lo Monte
J. Funct. Biomater. 2025, 16(6), 228; https://doi.org/10.3390/jfb16060228 - 19 Jun 2025
Viewed by 870
Abstract
This systematic review aimed to evaluate the potential of combining platelet-rich plasma (PRP) and polybutylene succinate (PBS) for the development of vascular grafts in patients undergoing chemotherapy. Relevant articles published in English or Italian were selected through a comprehensive search of MEDLINE (via [...] Read more.
This systematic review aimed to evaluate the potential of combining platelet-rich plasma (PRP) and polybutylene succinate (PBS) for the development of vascular grafts in patients undergoing chemotherapy. Relevant articles published in English or Italian were selected through a comprehensive search of MEDLINE (via PubMed) and the Cochrane Library. A total of ten screened articles and two additional relevant studies were included. The synthesis of results was conducted using digital tools, thoroughly reviewed by the authors. The quality assessment of the included studies revealed a medium-to-high risk of bias, with frequent limitations such as small sample sizes, experimental designs, and overall moderate to low methodological quality. Despite the heterogeneity of the findings, the available evidence suggests that radiocephalic graft placement and the use of PBS as a scaffold material, in combination with the growth factors contained in PRP, may improve clinical outcomes and reduce complications related to arteriovenous graft implantation. While promising, the current literature on this topic remains scarce and fragmented, underscoring the need for additional preclinical and clinical research. The proposed approach appears to hold potential for improving vascular access in oncology, but further in vivo validation is essential. This study received no external funding. Registration: PROSPERO ID CRD42025646724. Full article
(This article belongs to the Section Biomaterials for Cancer Therapies)
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17 pages, 901 KB  
Review
What Are the Best Biocompatible Materials for Extracorporeal Membrane Oxygenation
by Junya Hagiwara, Jeffrey D. DellaVolpe and Yuichi Matsuzaki
J. Funct. Biomater. 2025, 16(6), 226; https://doi.org/10.3390/jfb16060226 - 19 Jun 2025
Viewed by 1714
Abstract
Extracorporeal membrane oxygenation (ECMO) is a crucial life support therapy for patients with severe cardiac and respiratory failure. However, the complications associated with venoarterial ECMO (VA-ECMO), including thrombus formation, bleeding, and hemolysis, remain significant challenges that impact patient outcomes and healthcare costs. These [...] Read more.
Extracorporeal membrane oxygenation (ECMO) is a crucial life support therapy for patients with severe cardiac and respiratory failure. However, the complications associated with venoarterial ECMO (VA-ECMO), including thrombus formation, bleeding, and hemolysis, remain significant challenges that impact patient outcomes and healthcare costs. These complications primarily arise from blood–material interactions within the ECMO circuit, necessitating the development of biocompatible materials to optimize hemocompatibility. This review provides an updated overview of the latest advancements in VA-ECMO materials, focusing on cannula, oxygenators, and centrifugal pumps. Various surface modifications, such as heparin coatings, nitric oxide-releasing polymers, phosphorylcholine (PC)-based coatings, and emerging omniphobic surfaces, have been explored to mitigate thrombosis and bleeding risks. Additionally, novel oxygenator membrane technologies, including zwitterionic polymers and endothelial-mimicking coatings, offer promising strategies to enhance biocompatibility and reduce inflammatory responses. In centrifugal pumps, magnetic levitation systems and hybrid polymer-composite impellers have been introduced to minimize shear stress and thrombogenicity. Despite these advancements, no single material has fully addressed all complications, and further research is needed to refine surface engineering strategies. This review highlights the current progress in ECMO biomaterials and discusses future directions in developing more effective and durable solutions to improve patient safety and clinical outcomes. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering: Current Status and Advances)
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23 pages, 4339 KB  
Article
Electrospinning of Bovine Split Hide Collagen and Collagen/Glycosaminoglycan for a Study of Stem Cell Adhesion and Proliferation on the Mats: Influence of Composition and Structural Morphology
by Todorka G. Vladkova, Dilyana N. Gospodinova, Peter D. Dineff, Milena Keremidarska-Markova, Kamelia Hristova-Panusheva and Natalia Krasteva
J. Funct. Biomater. 2025, 16(6), 219; https://doi.org/10.3390/jfb16060219 - 12 Jun 2025
Cited by 1 | Viewed by 948
Abstract
Electrospun collagen-based fibrous mats are of increasing interest for cell culture, regenerative medicine, and tissue engineering. The focus of this investigation is on the assessment of the electrospinning ability of bovine split hide collagen (BSHC), the effect of glycosaminoglycan (GAG) incorporation on the [...] Read more.
Electrospun collagen-based fibrous mats are of increasing interest for cell culture, regenerative medicine, and tissue engineering. The focus of this investigation is on the assessment of the electrospinning ability of bovine split hide collagen (BSHC), the effect of glycosaminoglycan (GAG) incorporation on the mats’ structural morphology, and the impact on the adhesion and proliferation of human adipose-derived mesenchymal stem cells (hAD-MSCs). Electrospun mats were prepared using benign and fluoroalcohol solutions of BSHC and BSHC/GAGs under varied operation conditions. SEM observations and analysis were employed to characterize the structural morphology of the mats. Several parameters were used to evaluate the hAD-MSC behavior: cytotoxicity, cell morphology, cell number and spreading area, cytoskeleton, focal adhesion contacts, and cell proliferation. Electrospinning using benign solvents was impossible. However, fiber mats were successfully prepared from hexafluoropropanol (HFP) solutions. Different structural morphologies and fiber diameters of the electrospun mats were observed depending on the composition and concentration of the electrospinning solutions. Both BSHC and BSHC/GAG mats supported the in vitro adhesion, growth, and differentiation of hAD-MSCs, with some variations based on their composition and structural morphology. The absence of cytotoxicity and the good hAD-MSC adhesiveness make them promising substrates for cell adhesion, proliferation, and further stem cell differentiation. 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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19 pages, 5532 KB  
Article
In Vitro Biological Properties Assessment of 3D-Printed Hydroxyapatite–Polylactic Acid Scaffolds Intended for Bone Regeneration
by Eddy Shan, Cristina Chamorro, Ana Ferrández-Montero, Rosa M. Martin-Rodriguez, Begoña Ferrari, Antonio Javier Sanchez-Herencia, Leire Virto, María José Marín, Elena Figuero and Mariano Sanz
J. Funct. Biomater. 2025, 16(6), 218; https://doi.org/10.3390/jfb16060218 - 12 Jun 2025
Cited by 1 | Viewed by 1167
Abstract
This study evaluated the biological performance in vitro of two 3D-printed hydroxyapatite (HA) and polylactic acid (PLA) composite scaffolds with two different infill densities (50% [HA-PLA50] and 70% [HA-PLA70]). Comparative analysis using MG-63 cell cultures evaluated the following: (1) integrity after exposure to [...] Read more.
This study evaluated the biological performance in vitro of two 3D-printed hydroxyapatite (HA) and polylactic acid (PLA) composite scaffolds with two different infill densities (50% [HA-PLA50] and 70% [HA-PLA70]). Comparative analysis using MG-63 cell cultures evaluated the following: (1) integrity after exposure to various sterilization methods; (2) cell viability; (3) morphological characteristics; (4) cell proliferation; (5) cytotoxicity; (6) gene expression; and (7) protein synthesis. Ultraviolet radiation was the preferred sterilization method. Both scaffolds maintained adequate cell viability and proliferation over 7 days without significant differences in cytotoxicity. Notably, HA-PLA50 scaffolds demonstrated superior osteogenic potential, showing a significantly higher expression of collagen type I (COL1A1) and an increased synthesis of interleukins 6 and 8 (IL-6, IL-8) compared to HA-PLA70 scaffolds. While both scaffold types supported robust cell growth, the HA-PLA50 formulation exhibited enhanced bioactivity, suggesting a potential advantage for bone tissue engineering applications. These findings provide important insights for optimizing 3D-printed bone graft substitutes. Full article
(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration)
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18 pages, 5355 KB  
Article
Transparent 3-Layered Bacterial Nanocellulose as a Multicompartment and Biomimetic Scaffold for Co-Culturing Cells
by Karla Pollyanna Vieira de Oliveira, Michael Yilma Yitayew, Ana Paula Almeida Bastos, Stefanie Cristine Nied Mandrik, Luismar Marques Porto and Maryam Tabrizian
J. Funct. Biomater. 2025, 16(6), 208; https://doi.org/10.3390/jfb16060208 - 3 Jun 2025
Viewed by 1265
Abstract
Three-dimensional (3D) cell culture models are widely used to provide a more physiologically relevant microenvironment in which to host and study desired cell types. These models vary in complexity and cost, ranging from simple and inexpensive to highly sophisticated and costly systems. In [...] Read more.
Three-dimensional (3D) cell culture models are widely used to provide a more physiologically relevant microenvironment in which to host and study desired cell types. These models vary in complexity and cost, ranging from simple and inexpensive to highly sophisticated and costly systems. In this study, we introduce a novel translucent multi-compartmentalized stacked multilayered nanocellulose scaffold and describe its fabrication, characterization, and potential application for co-culturing multiple cell types. The scaffold consists of bacterial nanocellulose (BNC) layers separated by interlayers of a lower density of nanocellulose fibers. Using this system, we co-cultured the MDA-MB-231 cell line with two tumor-associated cell types, namely BC-CAFs and M2 macrophages, to simulate the tumor microenvironment (TME). Cells remained viable and metabolically active for up to 15 days. Confocal microscopy showed no signs of cell invasion. However, BC-CAFs and MDA-MB-231 cells were frequently observed within the same layer. The expression of breast cancer-related genes was analyzed to assess the downstream functionality of the cells. We found that the E-cadherin expression was 20% lower in cancer cells co-cultured in the multi-compartmentalized scaffold than in those cultured in 2D plates. Since E-cadherin plays a critical role in preventing the initial dissociation of epithelial cells from the primary tumor mass and is often downregulated in the tumor microenvironment in vivo, this finding suggests that our scaffold more effectively recapitulates the complexity of a tumor microenvironment. Full article
(This article belongs to the Section Bone Biomaterials)
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18 pages, 6890 KB  
Article
Synthesis of ε-Fe2–3N Particles for Magnetic Hyperthermia
by Soichiro Usuki, Tomoyuki Ogawa, Masaya Shimabukuro, Taishi Yokoi and Masakazu Kawashita
J. Funct. Biomater. 2025, 16(6), 203; https://doi.org/10.3390/jfb16060203 - 1 Jun 2025
Cited by 1 | Viewed by 1102
Abstract
Little research has focused on using iron nitride as thermoseed particles in magnetic hyperthermia, although magnetite (Fe3O4) is commonly used for this purpose. In the present study, we focus on iron nitride, especially ε-Fe2–3N. ε-Fe2–3N [...] Read more.
Little research has focused on using iron nitride as thermoseed particles in magnetic hyperthermia, although magnetite (Fe3O4) is commonly used for this purpose. In the present study, we focus on iron nitride, especially ε-Fe2–3N. ε-Fe2–3N particles were synthesized from hematite (α-Fe2O3) and sodium amide (NaNH2) under various synthesis conditions, and the heat-generation properties of the particles were investigated to reveal the synthesis conditions that lead to particles with notable heat-generation performance. The particles synthesized at 250 °C for 12 h increased the temperature of an agar phantom by approximately 20 °C under an alternating magnetic field (100 kHz, 125 Oe, 600 s), suggesting that ε-Fe2–3N particles can be used for magnetic hyperthermia. The analysis results for the particles synthesized under different conditions suggest that the heat-generation properties of ε-Fe2–3N were affected by several factors, including the nitrogen content, particle size, crystallite size, saturation magnetization, and coercive force. Full article
(This article belongs to the Special Issue Magnetic Materials for Medical Use)
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20 pages, 9010 KB  
Article
Polycaprolactone/Doped Bioactive Glass Composite Scaffolds for Bone Regeneration
by Ana Sofia Pádua, Manuel Pedro Fernandes Graça and Jorge Carvalho Silva
J. Funct. Biomater. 2025, 16(6), 200; https://doi.org/10.3390/jfb16060200 - 1 Jun 2025
Cited by 1 | Viewed by 1399
Abstract
Critical-size bone defects do not heal spontaneously and require external support, making bone regeneration a central challenge in tissue engineering. Polymeric/ceramic composite scaffolds offer a promising approach to mimic the structural and biological properties of bone. In this study, we aimed to evaluate [...] Read more.
Critical-size bone defects do not heal spontaneously and require external support, making bone regeneration a central challenge in tissue engineering. Polymeric/ceramic composite scaffolds offer a promising approach to mimic the structural and biological properties of bone. In this study, we aimed to evaluate the effect of different doping oxides in bioactive glass (BG) on the performance of polycaprolactone (PCL)-based composite scaffolds for bone tissue engineering applications. Composite scaffolds were fabricated using solvent casting, hot pressing, and salt-leaching techniques, combining PCL with 25 wt% of BG or doped BG containing 4 mol% of tantalum, zinc, magnesium, or niobium oxides, and 1 mol% of copper oxide. The scaffolds were characterized in terms of morphology, mechanical properties, and in vitro biological performance. All scaffolds exhibited a highly porous, interconnected structure. Mechanical compression tests indicated that elastic modulus increased with ceramic content, while doping had no measurable effect. Cytotoxicity assays confirmed biocompatibility across all scaffolds. Among the tested materials, the Zn-doped BG/PCL scaffold uniquely supported cell adhesion and proliferation and significantly enhanced alkaline phosphatase (ALP) activity—an early marker of osteogenic differentiation—alongside the Nb-doped scaffold. These results highlight the Zn-doped BG/PCL composite as a promising candidate for bone regeneration applications. Full article
(This article belongs to the Section Bone Biomaterials)
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13 pages, 3526 KB  
Article
Development of a Sustainable Bone Regeneration Material Using Apatite Paste Derived from Eggshell Waste
by Masatsugu Hirota, Chihiro Mochizuki, Toshitsugu Sakurai, Hiroyuki Mishima, Chikahiro Ohkubo and Takatsugu Yamamoto
J. Funct. Biomater. 2025, 16(6), 201; https://doi.org/10.3390/jfb16060201 - 1 Jun 2025
Cited by 1 | Viewed by 1402
Abstract
Apatite pastes derived from eggshell waste (BAp) were implanted onto the calvarial bone of rats, and bone formation was evaluated using X-ray μ-computed tomography (CT) and histological evaluation. BAp was mixed with distilled water to prepare a paste. Monoclinic hydroxyapatite of mineral resources [...] Read more.
Apatite pastes derived from eggshell waste (BAp) were implanted onto the calvarial bone of rats, and bone formation was evaluated using X-ray μ-computed tomography (CT) and histological evaluation. BAp was mixed with distilled water to prepare a paste. Monoclinic hydroxyapatite of mineral resources (HAp) was used as a control. A 5 mm diameter PTFE (polytetrafluoroethylene) tube was filled with apatite pastes and implanted in the calvarial bone of 9-week-old Sprague Dawley rats for 8 weeks. A larger radiopaque area, similar to that of native bone, was observed in the BAp paste-implanted specimens than that of HAp paste. The bone mineral density (BMD) value of the BAp paste was significantly higher than that of the HAp paste (p < 0.05). In the histological evaluation, new bone formation was noticed from the calvarial side for both apatite specimens, and HAp remained in the PTFE unlike BAp. The bone mass (BM) value of the BAp paste was significantly higher than that of the HAp paste (p < 0.05). SEM and XRD analyses revealed that BAp was microcrystalline and poorly crystalline. The promotion of new bone formation may contribute to the crystallinity and Mg content of BAp. BAp was found to be useful as a bone regeneration material. Full article
(This article belongs to the Section Bone Biomaterials)
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19 pages, 40479 KB  
Article
Caddisfly Silk-Polycaprolactone Foams: Physicochemical and Biological Properties of Nature-Inspired Biomaterials
by Mateusz M. Urbaniak, Mariusz Tszydel, Konrad Szustakiewicz, Aleksandra Szwed-Georgiou, Bartłomiej Kryszak, Marcin Włodarczyk, Sylwia Michlewska, Piotr Jóźwiak, Tomislav Ivankovic, Mikołaj K. Cybulski and Karolina Rudnicka
J. Funct. Biomater. 2025, 16(6), 199; https://doi.org/10.3390/jfb16060199 - 29 May 2025
Viewed by 1076
Abstract
The unique properties of insect silk have attracted attention for years to develop scaffolds for tissue engineering. Combining natural silks with synthetic polymers may benefit biocompatibility, mechanical strength, and elasticity. Silk-modified biomaterials are a promising choice for tissue engineering due to their versatility, [...] Read more.
The unique properties of insect silk have attracted attention for years to develop scaffolds for tissue engineering. Combining natural silks with synthetic polymers may benefit biocompatibility, mechanical strength, and elasticity. Silk-modified biomaterials are a promising choice for tissue engineering due to their versatility, biocompatibility, and many processing methods. This study investigated the physicochemical and biological properties of biocomposites formed by combining caddisfly silk (Hydropsyche angustipennis) and polycaprolactone (PCL). The PCL foams modified with caddisfly silk demonstrated full cytocompatibility and enhanced fibroblast adhesion and proliferation compared to unmodified PCL. These silk-modified PCL foams also induced NF-κB signaling, which is crucial for initiating tissue regeneration. Notably, the antimicrobial properties of the silk-modified PCL foams remained consistent with those of unmodified PCL, suggesting that the addition of silk did not alter this aspect of performance. The findings suggest that caddisfly silk-modified PCL foams present a promising solution for future medical and dental applications, emphasizing the potential of alternative silk sources in tissue engineering. Full article
(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)
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25 pages, 1292 KB  
Review
Nano/Micro-Enabled Modification and Innovation of Conventional Adjuvants for Next-Generation Vaccines
by Xingchi Liu, Xu Yang, Lu Tao, Xuanchen Li, Guoqiang Chen and Qi Liu
J. Funct. Biomater. 2025, 16(5), 185; https://doi.org/10.3390/jfb16050185 - 19 May 2025
Cited by 1 | Viewed by 2303
Abstract
The global spread of infectious diseases has raised public awareness of vaccines, highlighting their essential role in protecting public health. Among the components of modern vaccines, adjuvants have received increasing attention for boosting immune responses and enhancing efficacy. Recent advancements in adjuvant research, [...] Read more.
The global spread of infectious diseases has raised public awareness of vaccines, highlighting their essential role in protecting public health. Among the components of modern vaccines, adjuvants have received increasing attention for boosting immune responses and enhancing efficacy. Recent advancements in adjuvant research, particularly nanodelivery systems, have paved the way for developing more effective and safer adjuvants. This review outlines the properties, progress, and mechanisms of FDA-approved conventional adjuvants, focusing on their contributions to and challenges in vaccine success. Despite these advancements, conventional adjuvants still face suboptimal immunomodulatory effects, potential side effects, and limitations in targeting specific immune pathways. Nanodelivery systems have emerged as a transformative approach in adjuvant design, offering unique advantages such as enhancing vaccine stability, enabling controlled antigen release, and inducing specific immune responses. By addressing these limitations, nanocarriers improve the safety and efficacy of conventional adjuvants and drive the development of next-generation adjuvants for complex diseases. This review also explores strategies for incorporating nanodelivery systems into adjuvant development, emphasizing its role in optimizing vaccine formulations. By summarizing current challenges and recent advances, this review aims to provide valuable insights guiding future efforts in designing innovative adjuvants that meet the evolving needs of global immunization programs. Full article
(This article belongs to the Special Issue 15th Anniversary of JFB—Advanced Biomaterials for Drug Delivery)
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13 pages, 5872 KB  
Article
In Vivo Cell Migration and Growth Within Electrospun Porous Nanofibrous Scaffolds with Different Pore Sizes in a Mouse Pouch Model
by David C. Markel, Therese Bou-Akl, Bin Wu, Pawla Pawlitz, Xiaowei Yu, Liang Chen, Tong Shi and Weiping Ren
J. Funct. Biomater. 2025, 16(5), 181; https://doi.org/10.3390/jfb16050181 - 14 May 2025
Viewed by 986
Abstract
Cellular infiltration into traditional electrospun nanofibers (NFs) is limited due to their dense structures. We were able to obtain polycaprolactone (PCL) NFs with variable and defined pore sizes and thicknesses by using a customized programmed NF collector that controls the moving speed during [...] Read more.
Cellular infiltration into traditional electrospun nanofibers (NFs) is limited due to their dense structures. We were able to obtain polycaprolactone (PCL) NFs with variable and defined pore sizes and thicknesses by using a customized programmed NF collector that controls the moving speed during electrospinning. NFs obtained by this method were tested in vitro and have shown better cell proliferation within the NFs with larger pore sizes. This study investigated in vivo host cell migration and neovascularization within implanted porous PCL NF discs using a mouse pouch model. Four types of PCL NFs were prepared and classified based on the electrospinning speed: NF-zero (static control), NF-low (0.085 mm/min), NF-mid (0.158 mm/min) and NF-high (0.232 mm/min) groups. With the increase in the speed, we observed an increase in the pore area; NF-zero (11.6 ± 6.2 μm2), NF-low (37.4 ± 28.6 μm2), NF-mid (67.6 ± 54.8 μm2), and NF-high (292.3 ± 286.5 μm2) groups. The NFs were implanted into air pouches of BALB/cJ mice. Mice without NFs served as control. Animals were sacrificed at 7 and 28 days after the implantation. Pouch tissues with implanted NFs were collected for histology (n = three per group and time point). The efficiency of the tissue penetration into PCL NF sheets was closely linked to the pore size and area. NFs with the highest pore area had more efficient tissue migration and new blood vessel formation compared to those with a smaller pore area. No newly formed blood vessels were observed in NF-zero sheets up to 28 days. We believe that a porous NF scaffold with a controllable pore size and thickness has great potential for tissue repair/regeneration and for other healthcare applications. Full article
(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)
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14 pages, 2882 KB  
Article
Wharton’s Jelly Bioscaffolds Improve Cardiac Repair with Bone Marrow Mononuclear Stem Cells in Rats
by Luize Kremer Gamba, Laiza Kremer Gamba, Camila da Costa, Aline Luri Takejima, Rossana Baggio Simeoni, Isabella Cristina Mendes Rossa, Anna Clara Faidiga Silva, Julia Letícia de Bortolo, Marcos Antônio Denk, Seigo Nagashima, Carlos de Almeida Barbosa, Paulo Cesar Lock Silveira, Júlio César Francisco and Luiz César Guarita-Souza
J. Funct. Biomater. 2025, 16(5), 175; https://doi.org/10.3390/jfb16050175 - 12 May 2025
Viewed by 661
Abstract
This study assessed the impact of implanting mononuclear stem cells and Wharton’s Jelly (WJ), either separately or together, on left ventricular dysfunction following myocardial infarction in Wistar rats. Functional and histopathological parameters were analyzed, and a rat model of left anterior descending coronary [...] Read more.
This study assessed the impact of implanting mononuclear stem cells and Wharton’s Jelly (WJ), either separately or together, on left ventricular dysfunction following myocardial infarction in Wistar rats. Functional and histopathological parameters were analyzed, and a rat model of left anterior descending coronary artery ligation was used. Treatments included an intramyocardial injection of 0.9% sodium chloride (control, n = 14), decellularized WJ (n = 12), bone marrow-derived mononuclear cells (BMMC) (n = 12), and bone marrow-derived mononuclear cells (BMMC) combined with WJ (n = 15). Echocardiography assessed the left ventricular function and ejection fraction over four weeks. Histological and immunohistochemical analyses with anti-factor VIII evaluated angiogenesis and collagen types I and III. The results showed no statistically significant effect on ventricular remodeling 30 days post-acute myocardial infarction (AMI). Moreover, the infarct area was significantly smaller in the BMMC + WJ group compared to the control group, suggesting a potential benefit in reducing myocardial scarring. BMMC + WJ therapy demonstrated potential for functional improvement and infarct size reduction 30 days post-infarction. Further studies are needed to confirm its therapeutic benefits. Full article
(This article belongs to the Collection Feature Papers in Biomaterials for Healthcare Applications)
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33 pages, 10568 KB  
Review
Emerging Trends in Microfluidic Biomaterials: From Functional Design to Applications
by Jiaqi Lin, Lijuan Cui, Xiaokun Shi and Shuping Wu
J. Funct. Biomater. 2025, 16(5), 166; https://doi.org/10.3390/jfb16050166 - 8 May 2025
Cited by 3 | Viewed by 3538
Abstract
The rapid development of microfluidics has driven innovations in material engineering, particularly through its ability to precisely manipulate fluids and cells at microscopic scales. Microfluidic biomaterials, a cutting-edge interdisciplinary field integrating microfluidic technology with biomaterials science, are revolutionizing biomedical research. This review focuses [...] Read more.
The rapid development of microfluidics has driven innovations in material engineering, particularly through its ability to precisely manipulate fluids and cells at microscopic scales. Microfluidic biomaterials, a cutting-edge interdisciplinary field integrating microfluidic technology with biomaterials science, are revolutionizing biomedical research. This review focuses on the functional design and fabrication of organ-on-a-chip (OoAC) platforms via 3D bioprinting, explores the applications of biomaterials in drug delivery, cell culture, and tissue engineering, and evaluates the potential of microfluidic systems in advancing personalized healthcare. We systematically analyze the evolution of microfluidic materials—from silicon and glass to polymers and paper—and highlight the advantages of 3D bioprinting over traditional fabrication methods. Currently, despite significant advances in microfluidics in medicine, challenges in scalability, stability, and clinical translation remain. The future of microfluidic biomaterials will depend on combining 3D bioprinting with dynamic functional design, developing hybrid strategies that combine traditional molds with bio-printed structures, and using artificial intelligence to monitor drug delivery or tissue response in real time. We believe that interdisciplinary collaborations between materials science, micromachining, and clinical medicine will accelerate the translation of organ-on-a-chip platforms into personalized therapies and high-throughput drug screening tools. Full article
(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)
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15 pages, 3256 KB  
Article
Effect of Hyaluronan in Collagen Biomaterials on Human Macrophages and Fibroblasts In Vitro
by Nancy Avila-Martinez, Maren Pfirrmann, Madalena L. N. P. Gomes, Roman Krymchenko, Elly M. M. Versteeg, Marcel Vlig, Martijn Verdoes, Toin H. van Kuppevelt, Bouke K. H. L. Boekema and Willeke F. Daamen
J. Funct. Biomater. 2025, 16(5), 167; https://doi.org/10.3390/jfb16050167 - 8 May 2025
Viewed by 1913
Abstract
In adults, scars are formed after deep skin wound injuries like burns. However, the fetal microenvironment allows for scarless skin regeneration. One component that is abundantly present in the fetal extracellular matrix is hyaluronan (HA). To study whether biomaterials with HA improve wound [...] Read more.
In adults, scars are formed after deep skin wound injuries like burns. However, the fetal microenvironment allows for scarless skin regeneration. One component that is abundantly present in the fetal extracellular matrix is hyaluronan (HA). To study whether biomaterials with HA improve wound healing, type I collagen scaffolds with and without HA were prepared and characterized. Their immune effect was tested using macrophages and their phenotypes were analyzed through cell surface markers and cytokine expression after 48 h. Since fibroblasts are the main cellular component in the dermis, adult, fetal and eschar-derived cells were cultured on scaffolds for 14 days and evaluated using histology, gene and protein expression analyses. Biochemical assays demonstrated that HA was successfully incorporated and evenly distributed throughout the scaffolds. Macrophages (M0) cultured on Col I+HA scaffolds exhibited a profile resembling the M2c-like phenotype (CD206high, CD163high and IL10high). HA did not significantly affect gene expression in adult and fetal fibroblasts, but significantly reduced scarring-related genes, such as transforming growth factor beta 1 (TGFB1) and type X collagen alpha 1 chain (COL10A1), in myofibroblast-like eschar cells. These findings highlight the potential of incorporating HA into collagen-based skin substitutes to improve the wound healing response. Full article
(This article belongs to the Collection Feature Papers in Biomaterials for Tissue Engineering and Regenerative Medicine)
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45 pages, 18946 KB  
Review
Advancements in Musculoskeletal Tissue Engineering: The Role of Melt Electrowriting in 3D-Printed Scaffold Fabrication
by Kunal Ranat, Hong Phan, Suhaib Ellythy, Mitchell Kenter and Adil Akkouch
J. Funct. Biomater. 2025, 16(5), 163; https://doi.org/10.3390/jfb16050163 - 7 May 2025
Cited by 2 | Viewed by 2075
Abstract
Musculoskeletal tissue injuries of the bone, cartilage, ligaments, tendons, and skeletal muscles are among the most common injuries experienced in medicine and become increasingly problematic in cases of significant tissue damage, such as nonunion bone defects and volumetric muscle loss. Current gold standard [...] Read more.
Musculoskeletal tissue injuries of the bone, cartilage, ligaments, tendons, and skeletal muscles are among the most common injuries experienced in medicine and become increasingly problematic in cases of significant tissue damage, such as nonunion bone defects and volumetric muscle loss. Current gold standard treatment options for musculoskeletal injuries, although effective, have limited capability to fully restore native tissue structure and function. To overcome this challenge, three-dimensional (3D) printing techniques have emerged as promising therapeutic options for tissue regeneration. Melt electrowriting (MEW), a recently developed advanced 3D printing technique, has gained significant traction in the field of tissue regeneration because of its ability to fabricate complex customizable scaffolds via high-precision microfiber deposition. The tailorability at microscale levels offered by MEW allows for enhanced recapitulation of the tissue microenvironment. Here, we survey the recent contributions of MEW in advancing musculoskeletal tissue engineering. More specifically, we briefly discuss the principles and technical aspects of MEW, provide an overview of current printers on the market, review in-depth the latest biomedical applications in musculoskeletal tissue regeneration, and, lastly, examine the limitations of MEW and offer future perspectives. Full article
(This article belongs to the Special Issue Recent Advances in 3D Printing of Biomaterials)
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20 pages, 13885 KB  
Article
Biodegradable Double-Layer Hydrogels with Sequential Drug Release for Multi-Phase Collaborative Regulation in Scar-Free Wound Healing
by Xinyu Zhang, Qianhe Zu, Chunlin Deng, Xin Gao, Hongxu Liu, Yi Jin, Xinjian Yang and Enjun Wang
J. Funct. Biomater. 2025, 16(5), 164; https://doi.org/10.3390/jfb16050164 - 7 May 2025
Cited by 2 | Viewed by 1921
Abstract
Scarring is a prevalent and often undesirable outcome of the wound healing process, impacting millions worldwide. The complex and dynamic nature of wound healing, including hemostasis, inflammation, proliferation, and remodeling, necessitates precise, making it hard for stage-specific interventions to prevent pathological scarring. This [...] Read more.
Scarring is a prevalent and often undesirable outcome of the wound healing process, impacting millions worldwide. The complex and dynamic nature of wound healing, including hemostasis, inflammation, proliferation, and remodeling, necessitates precise, making it hard for stage-specific interventions to prevent pathological scarring. This study introduces a double-layer hydrogel system designed for sequential drug release, aligning with the stage-specific need for wound healing. The lower layer, containing curcumin-loaded chitosan nanoparticles, shows early anti-inflammatory and antioxidant effects, while the upper layer, with pirfenidone-encapsulated gelatin microspheres, presents late-stage anti-fibrotic activity. The hydrogel’s unique design, with varying degradation rates and mechanical properties in each layer, facilitates cascade drug release in synchrony with wound healing stages. Rapid release of curcumin from the lower layer promotes proliferation by mitigating inflammation and oxidative stress, while the sustained release of pirfenidone from the upper layer inhibits excessive fibrillation during late proliferation and remodeling. In a rat model of full-thickness skin defect, treatment with a double-layer hydrogel drug delivery system accelerated the wound closure, improved scar quality, and promoted the formation of hair follicles. Therefore, this innovative approach lays a promising foundation for future clinical applications in anti-scar therapies, offering a significant advancement in wound care and regenerative medicine. Full article
(This article belongs to the Special Issue Biomaterials for Wound Healing and Tissue Repair)
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15 pages, 3084 KB  
Article
Tumor-Treating Fields Alter Nanomechanical Properties of Pancreatic Ductal Adenocarcinoma Cells Co-Cultured with Extracellular Matrix
by Tanmay Kulkarni, Sreya Banik, Debabrata Mukhopadhyay, Hani Babiker and Santanu Bhattacharya
J. Funct. Biomater. 2025, 16(5), 160; https://doi.org/10.3390/jfb16050160 - 3 May 2025
Viewed by 1086
Abstract
Tumor-Treating Fields (TTFields), a novel therapeutic avenue, is approved for therapy in Glioblastoma multiforme, malignant pleural mesothelioma, and metastatic non-small cell lung cancer (NSCLC). In pancreatic ductal adenocarcinoma (PDAC), several clinical trials are underway to improve outcomes, yet a significant knowledge gap prevails [...] Read more.
Tumor-Treating Fields (TTFields), a novel therapeutic avenue, is approved for therapy in Glioblastoma multiforme, malignant pleural mesothelioma, and metastatic non-small cell lung cancer (NSCLC). In pancreatic ductal adenocarcinoma (PDAC), several clinical trials are underway to improve outcomes, yet a significant knowledge gap prevails involving the cell-extracellular matrix (ECM) crosstalk. Herein, we hypothesized that treatment with TTFields influence this crosstalk, which is reflected by the dynamic alteration in nanomechanical properties (NMPs) of cells and the ECM in a co-culture system. We employed an ECM gel comprising collagen, fibronectin, and laminin mixed in 100:1:1 stoichiometry to co-culture of Panc1 and AsPC1 individually. This ECM mixture mimics the in vivo tumor microenvironment closely when compared to the individual ECM components studied before. A comprehensive frequency-dependent study revealed the optimal TTFields frequency to be 150 kHz. We also observed that irrespective of the ECM’s presence, TTFields increase cell membrane stiffness and decrease deformation several-folds in both Panc1 and AsPC1 cells at both 48 h and 72 h. Although adhesion for AsPC1 decreased at 48 h, at 72 h it was observed to increase irrespective of ECM’s presence. Moreover, it significantly alters the NMPs of ECM gels when co-cultured with PDAC cell lines. However, AsPC1 cells were observed to be more detrimental to these changes. Lastly, we attribute the stiffness changes in Panc1 cells to the membrane F-actin reorganization in the presence of TTFields. This study paves a path to study complex PDAC TME as well as the effect of various chemotherapeutic agents on such TME with TTFields in the future. Full article
(This article belongs to the Section Biomaterials for Cancer Therapies)
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17 pages, 1502 KB  
Review
Peripheral Nerve Protection Strategies: Recent Advances and Potential Clinical Applications
by Weronika Radecka, Wiktoria Nogalska and Maria Siemionow
J. Funct. Biomater. 2025, 16(5), 153; https://doi.org/10.3390/jfb16050153 - 24 Apr 2025
Cited by 2 | Viewed by 3176
Abstract
Peripheral nerve injuries (PNIs) are a significant clinical challenge, often resulting in persistent sensory and motor deficits despite surgical repair. Autologous nerve grafts remain the gold standard for repair; however, outcomes are frequently suboptimal due to donor site morbidity and inconsistent functional recovery. [...] Read more.
Peripheral nerve injuries (PNIs) are a significant clinical challenge, often resulting in persistent sensory and motor deficits despite surgical repair. Autologous nerve grafts remain the gold standard for repair; however, outcomes are frequently suboptimal due to donor site morbidity and inconsistent functional recovery. A major obstacle in nerve regeneration is the formation of postoperative adhesions and fibrosis, which impede healing and necessitate revision surgeries. Nerve protectors from biological, synthetic, and hybrid materials offer a promising tissue engineering strategy to enhance nerve regeneration. These protectors are applied as a protective barrier when a nerve is severed without the gap, allowing for direct repair. They provide mechanical support and reduce scarring. Biocompatible biological wraps, including vascularized fat flaps, vein wraps, collagen-based materials, human amniotic membrane (hAM), porcine small intestinal submucosa (PSIS), and chitosan, modulate immune responses and promote vascularization. Synthetic alternatives, like polycaprolactone (PCL), provide mechanical stability with controlled degradation. Hybrid wraps, such as PCL-amnion, combine the benefits of both. Despite optimistic results, the heterogeneity of study methodologies hinders direct comparisons and standardization. This review highlights the latest developments in nerve wraps, their clinical applications, limitations, and future potential, guiding clinicians in selecting the most appropriate materials for peripheral nerve repair. 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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51 pages, 12197 KB  
Review
Recent Trends in the Application of Cellulose-Based Hemostatic and Wound Healing Dressings
by Clemence Futila Bukatuka, Bricard Mbituyimana, Lin Xiao, Abeer Ahmed Qaed Ahmed, Fuyu Qi, Manjilla Adhikari, Zhijun Shi and Guang Yang
J. Funct. Biomater. 2025, 16(5), 151; https://doi.org/10.3390/jfb16050151 - 23 Apr 2025
Cited by 3 | Viewed by 4809
Abstract
Rapid hemostasis and wound healing are crucial severe trauma treatment. Natural mechanisms often prove insufficient, spurring research for innovative biomaterials. This review focuses on cellulose-based materials, which are promising due to their absorbency, biocompatibility, and processability. The novelty lies in exploring how these [...] Read more.
Rapid hemostasis and wound healing are crucial severe trauma treatment. Natural mechanisms often prove insufficient, spurring research for innovative biomaterials. This review focuses on cellulose-based materials, which are promising due to their absorbency, biocompatibility, and processability. The novelty lies in exploring how these materials promote clotting and tissue regeneration. They operate via extrinsic and intrinsic mechanisms. Extrinsically, they create a matrix at the wound to activate coagulation; intrinsically, they maintain clotting factors. Additionally, they aid healing through physical, chemical, and biological means, such as maintaining moisture, incorporating antimicrobial agents, and stimulating cell activity. The innovative fabrication strategies include material selection and chemical modification. Techniques like oxidation enhance performance. Structural engineering methods like freeze-drying and 3D printing optimize porosity and alignment. Cellulose-based dressings are versatile and effective in various forms. They address different wound needs and show benefits like rapid coagulation and tissue repair. This review also covers challenges and future trends, emphasizing the need to enhance mechanical properties and biodegradability. Further, new technologies offer potential improvements to the nanocomposites. Overall, continued research on cellulose-based dressing is vital, and unlocking their potential could revolutionize wound care, providing suitable solutions for trauma management. Full article
(This article belongs to the Special Issue Recent Studies on Biomaterials for Tissue Repair and Regeneration)
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26 pages, 5083 KB  
Review
Injectable Stem Cell-Based Therapies for Myocardial Regeneration: A Review of the Literature
by Marissa Guo, Tatsuya Watanabe and Toshiharu Shinoka
J. Funct. Biomater. 2025, 16(5), 152; https://doi.org/10.3390/jfb16050152 - 23 Apr 2025
Viewed by 2231
Abstract
Stem cell-based therapies are an emerging treatment modality aimed at replenishing lost cardiomyocytes and improving myocardial function after cardiac injury. This review examines the current state of research on injectable stem cell therapies in the setting of cardiovascular disease given their relative simplicity [...] Read more.
Stem cell-based therapies are an emerging treatment modality aimed at replenishing lost cardiomyocytes and improving myocardial function after cardiac injury. This review examines the current state of research on injectable stem cell therapies in the setting of cardiovascular disease given their relative simplicity and ability for deep myocardial tissue penetration. Various methods of cell delivery, ranging in level of invasiveness and procedural complexity, have been developed, and numerous cell types have been studied as potential sources of stem cells, each with distinct advantages and disadvantages. We discuss key challenges associated with this approach, including low stem cell retention after transplantation and the innovative biomolecular strategies that have been explored to address this issue. Overall, investigations into the application of stem cells toward cardiac regeneration remain predominantly in the preclinical stage with a number of small, early-phase clinical trials. However, continued scientific advancements in stem cell technology may provide transformative treatment options for patients with heart failure, offering improved survival and quality of life. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering: Current Status and Advances)
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16 pages, 2252 KB  
Article
Impact of Vitamin D3 Functionalization on the Osteogenic Capacity of Bioinspired 3D Scaffolds Based on Ce-Doped Bioactive Glass and Spongia Agaricina
by Ana-Maria Seciu-Grama, Sorana Elena Lazăr, Simona Petrescu, Oana Cătălina Mocioiu, Oana Crăciunescu and Irina Atkinson
J. Funct. Biomater. 2025, 16(4), 141; https://doi.org/10.3390/jfb16040141 - 14 Apr 2025
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Abstract
Reconstruction of extensive bone defects due to age, trauma, or post-illness conditions remains challenging. Biomimetic scaffolds with osteogenic capabilities have been proposed as an alternative to the classical autograft and allograft implants. Three-dimensional scaffolds were obtained based on Ce-doped mesoporous bioactive glass (MBG) [...] Read more.
Reconstruction of extensive bone defects due to age, trauma, or post-illness conditions remains challenging. Biomimetic scaffolds with osteogenic capabilities have been proposed as an alternative to the classical autograft and allograft implants. Three-dimensional scaffolds were obtained based on Ce-doped mesoporous bioactive glass (MBG) and Spongia agaricina (SA) as sacrificial templates functionalized with vitamin D3. The study aimed to investigate the effect of vitamin D3 functionalization on the optimal variant of a 3D scaffold doped with 3 mol% ceria, selected in our previous work based on its biological and physicochemical properties. Scanning electron microscopy (SEM) images of the non-functionalized/functionalized scaffolds revealed a porous structure with interconnected pores ranging from 100 to 350 μm. Fourier transform infrared spectroscopy (FTIR) and SEM analysis confirmed the surface functionalization. Cytotoxicity evaluation showed that all investigated scaffolds do not exhibit cytotoxicity and genotoxicity toward the Saos-2 osteosarcoma cell line. Moreover, the study demonstrated that functionalization with vitamin D3 enhanced osteogenic activity in dental pulp stem cells (DPSCs) by increasing calcium deposition and osteocalcin secretion, as determined by Alizarin red stain and a colorimetric ELISA kit, as a result of its synergistic action with cerium ions. The results showed that the Ce-doped MBG scaffold functionalized with vitamin D3 had the potential for applications in bone regeneration. Full article
(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration)
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15 pages, 4954 KB  
Article
Evaluation of the Characteristics of Digital Light Processing 3D-Printed Magnesium Calcium Phosphate for Bone Regeneration
by Peng Zhang, Meiling Zhang, Yoo-Na Jung, Seong-Won Choi, Yong-Seok Lee, Geelsu Hwang and Kwi-Dug Yun
J. Funct. Biomater. 2025, 16(4), 139; https://doi.org/10.3390/jfb16040139 - 14 Apr 2025
Viewed by 1086
Abstract
Recent advancements in three-dimensional (3D) printing technology, particularly digital light processing (DLP) 3D printing, have enabled the customization of bone substitutes with specific shapes that match bone defect sizes and geometries. Magnesium calcium phosphate (MCP) has gained considerable attention due to its strong [...] Read more.
Recent advancements in three-dimensional (3D) printing technology, particularly digital light processing (DLP) 3D printing, have enabled the customization of bone substitutes with specific shapes that match bone defect sizes and geometries. Magnesium calcium phosphate (MCP) has gained considerable attention due to its strong mechanical properties, degradability, and ability to promote bone regeneration. In this study, we prepared MCP samples with five different molar ratios via DLP 3D printing. We analyzed the physicochemical properties of these five groups, including phase compositions and microstructures, which were examined using X-ray diffraction and scanning electron microscopy, respectively. Additionally, we assessed the effects of MCP on material density and shrinkage. Biaxial flexural strength and degradation rate were evaluated; biological properties were examined through WST-8 analysis and alkaline phosphatase activity assays. Among the tested samples, MCP1/1 exhibited the highest strength. A higher proportion of magnesium phosphate in MCP corresponded to an increased degradation rate. Cell response observations in the WST-8 assay indicated that cell proliferation was better in the MCP1/1 group than in the other groups on days 4 and 7 of culturing. Alkaline phosphatase activity assays demonstrated that MCP1/1 exhibited higher activity than calcium phosphate. Our findings suggest that MCP1/1 can be used effectively in bone-tissue-engineering applications. Full article
(This article belongs to the Special Issue State of the Art: Three-Dimensional Printing Materials and Regenerative Medicine)
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21 pages, 2270 KB  
Review
Role of Endophytic Fungi in the Biosynthesis of Metal Nanoparticles and Their Potential as Nanomedicines
by Hanadi Sawalha, Simon E. Moulton, Andreas Winkel, Meike Stiesch and Bita Zaferanloo
J. Funct. Biomater. 2025, 16(4), 129; https://doi.org/10.3390/jfb16040129 - 3 Apr 2025
Viewed by 1867
Abstract
Metal nanoparticles (MNPs) produced through biosynthesis approaches have shown favourable physical, chemical, and antimicrobial characteristics. The significance of biological agents in the synthesis of MNPs has been acknowledged as a promising alternative to conventional approaches such as physical and chemical methods, which are [...] Read more.
Metal nanoparticles (MNPs) produced through biosynthesis approaches have shown favourable physical, chemical, and antimicrobial characteristics. The significance of biological agents in the synthesis of MNPs has been acknowledged as a promising alternative to conventional approaches such as physical and chemical methods, which are confronted with certain challenges. To meet these challenges, the use of endophytic fungi as nano-factories for the synthesis of MNPs has become increasingly popular worldwide in recent times. This review provides an overview of the synthesis of MNPs using endophytic fungi, the mechanisms involved, and their important biomedical applications. A special focus on different biomedical applications of MNPs mediated endophytic fungi involved their antibacterial, antifungal, antiviral, and anticancer applications and their potential as drug delivery agents. Furthermore, this review highlights the significance of the use of endophytic fungi for the green synthesis of MNPs and discusses the benefits, challenges, and prospects in this field. Full article
(This article belongs to the Collection Feature Papers in Antibacterial Biomaterials)
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16 pages, 748 KB  
Article
Fabrication of a 3D Corneal Model Using Collagen Bioink and Human Corneal Stromal Cells
by Alexander J. Choi, Brenna S. Hefley, Hannah A. Strobel, Sarah M. Moss, James B. Hoying, Sarah E. Nicholas, Shadi Moshayedi, Jayoung Kim and Dimitrios Karamichos
J. Funct. Biomater. 2025, 16(4), 118; https://doi.org/10.3390/jfb16040118 - 28 Mar 2025
Cited by 1 | Viewed by 1514
Abstract
Corneal transplantation remains a critical treatment option for individuals with corneal disorders, but it faces challenges such as rejection, high associated medical costs, and donor scarcity. A promising alternative for corneal replacement involves fabricating artificial cornea from a patient’s own cells. Our study [...] Read more.
Corneal transplantation remains a critical treatment option for individuals with corneal disorders, but it faces challenges such as rejection, high associated medical costs, and donor scarcity. A promising alternative for corneal replacement involves fabricating artificial cornea from a patient’s own cells. Our study aimed to leverage bioprinting to develop a corneal model using human corneal stromal cells embedded in a collagen-based bioink. We generated both cellular and acellular collagen I (COL I) constructs. Cellular constructs were cultured for up to 4 weeks, and gene expression analysis was performed to assess extracellular matrix (ECM) remodeling and fibrotic markers. Our results demonstrated a significant decrease in the expression of COL I, collagen III (COL III), vimentin (VIM), and vinculin (VCL), indicating a dynamic remodeling process towards a more physiologically relevant corneal ECM. Overall, our study provides a foundational framework for developing customizable, corneal replacements using bioprinting technology. Further research is necessary to optimize the bioink composition and evaluate the functional and biomechanical properties of these bioengineered corneas. Full article
(This article belongs to the Collection Feature Papers in Biomaterials for Healthcare Applications)
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