Journal of Functional Biomaterials

36 pages, 3511 KiB

Open AccessEditor’s ChoiceReview

Three-Dimensional Bioprinting for Intervertebral Disc Regeneration

by Md Amit Hasan Tanvir, Md Abdul Khaleque, Junhee Lee, Jong-Beom Park, Ga-Hyun Kim, Hwan-Hee Lee and Young-Yul Kim

J. Funct. Biomater. 2025, 16(3), 105; https://doi.org/10.3390/jfb16030105 - 14 Mar 2025

Viewed by 1462

Abstract

The rising demand for organ transplants and the need for precise tissue models have positioned the in vitro biomanufacturing of tissues and organs as a pivotal area in regenerative treatment. Considerable development has been achieved in growing tissue-engineered intervertebral disc (IVD) scaffolds, designed [...] Read more.

The rising demand for organ transplants and the need for precise tissue models have positioned the in vitro biomanufacturing of tissues and organs as a pivotal area in regenerative treatment. Considerable development has been achieved in growing tissue-engineered intervertebral disc (IVD) scaffolds, designed to meet stringent mechanical and biological compatibility criteria. Among the cutting-edge approaches, 3D bioprinting stands out due to its unparalleled capacity to organize biomaterials, bioactive molecules, and living cells with high precision. Despite these advancements, polymer-based scaffolds still encounter limitations in replicating the extracellular matrix (ECM)-like environment, which is fundamental for optimal cellular activities. To overcome these challenges, integrating polymers with hydrogels has been recommended as a promising solution. This combination enables the advancement of porous scaffolds that nurture cell adhesion, proliferation, as well as differentiation. Additionally, bioinks derived from the decellularized extracellular matrix (dECM) have exhibited potential in replicating biologically relevant microenvironments, enhancing cell viability, differentiation, and motility. Hydrogels, whether derived from natural sources involving collagen and alginate or synthesized chemically, are highly valued for their ECM-like properties and superior biocompatibility. This review will explore recent advancements in techniques and technologies for IVD regeneration. Emphasis will be placed on identifying research gaps and proposing strategies to bridge them, with the goal of accelerating the translation of IVDs into clinical applications. Full article

(This article belongs to the Special Issue Three-Dimensional-Printable Biomaterials for Bone Regeneration)

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22 pages, 4851 KiB

Open AccessEditor’s ChoiceArticle

Porous Hydrogels Prepared by Two-Step Gelation Method for Bone Regeneration

by Yongzhi Li, Jiangshan Liu, Jiawei Wei, Li Yuan, Jiaxin Hu, Siluo Dai, Yubao Li and Jidong Li

J. Funct. Biomater. 2025, 16(3), 100; https://doi.org/10.3390/jfb16030100 - 13 Mar 2025

Cited by 1 | Viewed by 1022

Abstract

Hierarchical porous hydrogels possess advantageous characteristics that facilitate cell adhesion, promote tissue growth, and enhance angiogenesis and osteogenesis. In this study, porous composite hydrogels were successfully prepared by a two-step gelation method with sodium alginate (SA), gelatin (GEL), and calcium hydrogen phosphate (DCP) [...] Read more.

Hierarchical porous hydrogels possess advantageous characteristics that facilitate cell adhesion, promote tissue growth, and enhance angiogenesis and osteogenesis. In this study, porous composite hydrogels were successfully prepared by a two-step gelation method with sodium alginate (SA), gelatin (GEL), and calcium hydrogen phosphate (DCP) as the main components. The fabricated porous hydrogels initially featured small pores (approximately 60 μm), and gradually evolved to large pores (exceeding 250 μm) during the gradual degradation in the cellular microenvironment. In vitro cell culture experiments indicated that these hydrogels could enhance the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells due to the hierarchical porous structure and the incorporation of DCP. Subcutaneous implantation and cranial defect repair experiments in Sprague−Dawley rats further confirmed that the small initial pore size of hydrogel scaffolds can provide more sites for cell adhesion. Additionally, the gradual degradation to form large pores was conducive to cell/tissue growth and blood vessel formation, ultimately being beneficial for vascularized bone regeneration. In summary, this study proposes an innovative strategy for developing porous hydrogels with gradual degradation for functional bone regeneration. Full article

(This article belongs to the Section Bone Biomaterials)

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25 pages, 10472 KiB

Open AccessEditor’s ChoiceArticle

Nanoparticle-Enhanced Collagen Hydrogels for Chronic Wound Management

by Alexandra Cătălina Bîrcă, Mihai Alexandru Minculescu, Adelina-Gabriela Niculescu, Ariana Hudiță, Alina Maria Holban, Adina Alberts and Alexandru Mihai Grumezescu

J. Funct. Biomater. 2025, 16(3), 91; https://doi.org/10.3390/jfb16030091 - 5 Mar 2025

Cited by 6 | Viewed by 2264

Abstract

Chronic wound infections present a persistent medical challenge; however, advancements in wound dressings and antimicrobial nanomaterials offer promising solutions for improving healing outcomes. This study introduces a hydrothermal synthesis approach for producing zinc oxide (ZnO) and copper oxide (CuO) nanoparticles, subsequently incorporated into [...] Read more.

Chronic wound infections present a persistent medical challenge; however, advancements in wound dressings and antimicrobial nanomaterials offer promising solutions for improving healing outcomes. This study introduces a hydrothermal synthesis approach for producing zinc oxide (ZnO) and copper oxide (CuO) nanoparticles, subsequently incorporated into PLGA microspheres and embedded within collagen hydrogels. The nanoparticles’ physicochemical properties were characterized using X-ray diffraction (XRD) to confirm crystalline structure, scanning electron microscopy (SEM) for surface morphology, and Fourier-transform infrared spectroscopy (FT-IR) to verify functional groups and successful hydrogel integration. The hydrogels were tested for antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, which are key pathogens in chronic wounds. Biocompatibility was assessed using the human HaCat keratinocyte cell line. Both ZnO- and CuO-loaded hydrogels exhibited broad-spectrum antimicrobial efficacy. Cytocompatibility tests demonstrated that both ZnO- and CuO-loaded hydrogels sustain cell viability and proliferation, highlighting their biocompatibility and suitability for chronic wound healing applications, with superior biological performance of ZnO-loaded hydrogels. Furthermore, the distinct antimicrobial profiles of ZnO and CuO hydrogels suggest their tailored use based on wound microbial composition, with CuO hydrogels excelling in antibacterial applications and ZnO hydrogels showing potential for antifungal treatments. These results underscore the potential of nanoparticle-based collagen hydrogels as innovative therapeutic tools for managing chronic wounds. Full article

(This article belongs to the Special Issue Active Biomedical Materials and Their Applications, 2nd Edition)

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23 pages, 9992 KiB

Open AccessEditor’s ChoiceArticle

Electrospun Polycaprolactone–Gelatin Fibrils Enabled 3D Hydrogel Microcapsules for Biomedical Applications

by Felix Tettey-Engmann, Thakur Sapkota, Sita Shrestha, Narayan Bhattarai and Salil Desai

J. Funct. Biomater. 2025, 16(3), 85; https://doi.org/10.3390/jfb16030085 - 2 Mar 2025

Viewed by 989

Abstract

Microcapsules provide a microenvironment by improving the protection and delivery of cells and drugs to specific tissue areas, promoting cell integration and tissue regeneration. Effective microcapsules must not only be permeable for micronutrient diffusion but mechanically stable. Alginate hydrogel is one of the [...] Read more.

Microcapsules provide a microenvironment by improving the protection and delivery of cells and drugs to specific tissue areas, promoting cell integration and tissue regeneration. Effective microcapsules must not only be permeable for micronutrient diffusion but mechanically stable. Alginate hydrogel is one of the commonly used biomaterials for fabricating microcapsules due to its gel-forming ability and low toxicity. However, its mechanical instability, inertness, and excessive porosity have impeded its use. Embedding nanofibrils in the alginate hydrogel microcapsules improves their biological and mechanical properties. In this research, electrospun composite nanofibers of PCL–gelatin (PG) were first fabricated, characterized, and cryoground. The filtered and cryoground powder solution was mixed with the alginate solution and through electrospray, fabricated into microcapsules. Parameters such as flow rate, voltage, and hydrogel composition, which are critical in the electrostatic encapsulation process, were optimized. The microcapsules were further immersed in different solvent environments (DI water, complete media, and PBS), which were observed and compared for their morphology, size distribution, and mechanical stability properties. The average diameters of the PG nanofibers ranged between 0.2 and 2 μm, with an average porosity between 58 and 73%. The average size of the microcapsules varied between 300 and 900 μm, depending on the solvent environment. Overall, results showed an improved alginate 3D hydrogel network suitable for biomedical applications. Full article

(This article belongs to the Special Issue Functionalized Polymeric Biomaterials: Design and Applications, 2nd Edition)

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16 pages, 8845 KiB

Open AccessEditor’s ChoiceArticle

Cu-MOF-Decorated 3D-Printed Scaffolds for Infection Control and Bone Regeneration

by Ting Zhu, Qi Ni, Wenjie Wang, Dongdong Guo, Yixiao Li, Tianyu Chen, Dongyang Zhao, Xingyu Ma and Xiaojun Zhang

J. Funct. Biomater. 2025, 16(3), 83; https://doi.org/10.3390/jfb16030083 - 1 Mar 2025

Cited by 1 | Viewed by 1387

Abstract

Infection control and bone regeneration remain critical challenges in bone defect treatment. We developed a 3D-printed scaffold incorporating copper-based metal–organic framework-74 (Cu-MOF-74) within a polycaprolactone/hydroxyapatite composite. The synthesized Cu-MOF-74 exhibited a well-defined crystalline structure and rod-like morphology, as confirmed by TEM, EDS, FTIR, [...] Read more.

Infection control and bone regeneration remain critical challenges in bone defect treatment. We developed a 3D-printed scaffold incorporating copper-based metal–organic framework-74 (Cu-MOF-74) within a polycaprolactone/hydroxyapatite composite. The synthesized Cu-MOF-74 exhibited a well-defined crystalline structure and rod-like morphology, as confirmed by TEM, EDS, FTIR, and XRD analyses. The scaffolds exhibited hierarchical pores (100–200 μm) and demonstrated tunable hydrophilicity, as evidenced by the water contact angles decreasing from 103.3 ± 2.02° (0% Cu-MOF-74) to 63.60 ± 1.93° (1% Cu-MOF-74). A biphasic Cu²⁺ release profile was observed from the scaffolds, reaching cumulative concentrations of 98.97 ± 3.10 ppm by day 28. Antimicrobial assays showed concentration-dependent efficacy, with 1% Cu-MOF-74 scaffolds achieving 90.07 ± 1.94% and 80.03 ± 2.17% inhibition against Staphylococcus aureus and Escherichia coli, respectively. Biocompatibility assessments using bone marrow-derived mesenchymal stem cells revealed enhanced cell proliferation at Cu-MOF-74 concentrations ≤ 0.2%, while concentrations ≥ 0.5% induced cytotoxicity. Osteogenic differentiation studies highlighted elevated alkaline phosphatase activity and mineralization in scaffolds with 0.05–0.2% Cu-MOF-74 scaffolds, particularly at 0.05% Cu-MOF-74 scaffolds, which exhibited the highest calcium deposition and upregulation of bone sialoprotein and osteopontin expression. These findings demonstrate the dual functional efficacy of Cu-MOF-74/PCL/HAp scaffolds in promoting both infection control and bone regeneration. These optimized Cu-MOF-74 concentrations (0.05–0.2%) effectively balance antimicrobial and osteogenic properties, presenting a promising strategy for bone defect repair in clinical applications. Full article

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

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55 pages, 4225 KiB

Open AccessEditor’s ChoiceSystematic Review

Blood Plasma, Fibrinogen or Fibrin Biomaterial for the Manufacturing of Skin Tissue-Engineered Products and Other Dermatological Treatments: A Systematic Review

by Álvaro Sierra-Sánchez, Raquel Sanabria-de la Torre, Ana Ubago-Rodríguez, María I. Quiñones-Vico, Trinidad Montero-Vílchez, Manuel Sánchez-Díaz and Salvador Arias-Santiago

J. Funct. Biomater. 2025, 16(3), 79; https://doi.org/10.3390/jfb16030079 - 22 Feb 2025

Cited by 1 | Viewed by 1825

Abstract

The use of blood plasma, fibrinogen or fibrin, a natural biomaterial, has been widely studied for the development of different skin tissue-engineered products and other dermatological treatments. This systematic review reports the preclinical and clinical studies which use it alone or combined with [...] Read more.

The use of blood plasma, fibrinogen or fibrin, a natural biomaterial, has been widely studied for the development of different skin tissue-engineered products and other dermatological treatments. This systematic review reports the preclinical and clinical studies which use it alone or combined with other biomaterials and/or cells for the treatment of several dermatological conditions. Following the PRISMA 2020 Guidelines, 147 preclinical studies have revealed that the use of this biomaterial as a wound dressing or as a monolayer (one cell type) skin substitute are the preferred strategies, mainly for the treatment of excisional or surgical wounds. Moreover, blood plasma is mainly used alone although its combination with other biomaterials such as agarose, polyethylene glycol or collagen has also been reported to increase its wound healing potential. However, most of the 17 clinical reviewed evaluated its use for the treatment of severely burned patients as a wound dressing or bilayer (two cell types) skin substitute. Although the number of preclinical studies evaluating the use of blood plasma as a dermatological treatment has increased during the last fifteen years, this has not been correlated with a wide variety of clinical studies. Its safety and wound healing potential have been proved; however, the lack of a standard model and the presence of several approaches have meant that its translation to a clinical environment is still limited. A higher number of clinical studies should be carried out in the coming years to set a standard wound healing strategy for each dermatological disease. Full article

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

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14 pages, 4619 KiB

Open AccessEditor’s ChoiceArticle

Cobalt-Incorporated Hydroxyapatite Conditioned Media Promotes In Vitro Scratch Wound Healing and Mesenchymal Stem Cell Migration

by Weerapat Leelasangsai, Krongrat Thummachot, Puttita Thammasarnsophon, Autcharaporn Srion, Jintamai Suwanprateeb and Somying Patntirapong

J. Funct. Biomater. 2025, 16(3), 72; https://doi.org/10.3390/jfb16030072 - 20 Feb 2025

Viewed by 1068

Abstract

Cell migration of mesenchymal stem cells (MSCs) is critical for bone healing and remodeling. Cobalt is a well-known hypoxia mimic, which can enhance MSC migration. Therefore, the objective of this study was to investigate the migratory response of MSCs to a developed cobalt-incorporated [...] Read more.

Cell migration of mesenchymal stem cells (MSCs) is critical for bone healing and remodeling. Cobalt is a well-known hypoxia mimic, which can enhance MSC migration. Therefore, the objective of this study was to investigate the migratory response of MSCs to a developed cobalt-incorporated hydroxyapatite (HACo) material. HACo was fabricated by a simple ion exchange procedure at concentrations ranging from 40 to 8000 μM into disc shape. HACo discs were incubated in the media and conditioned media (CM; HACo_CM) were collected for MSC culture. HA_CM served as a control. MSCs were cultured until reaching 90% confluence before the wound was generated by scraping. Time-lapse imaging of wound migration was monitored, recorded, and assessed. Statistical analysis was performed by one-way ANOVA followed by a Dunnett’s test. The wound area gradually declined from 0 to 40 h for all samples. HACo_CM at 40 µM (HACo40_CM) promoted wound closure at the early period of wound healing. Both HACo40_CM and HACo8000_CM enhanced the distance and velocity of individual cell migration. However, only HACo40_CM affected cell persistence and direction at the early period of cell migration. Exposure to HACo_CM accelerated the speed of MSC migration, which is necessary for wound healing. The migratory ability of individual cells could help the rate of wound healing. Therefore, HACo materials may serve as potential biomaterials for enhanced bone healing. Full article

(This article belongs to the Section Bone Biomaterials)

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22 pages, 6166 KiB

Open AccessEditor’s ChoiceArticle

Schiff Base-Crosslinked Tetra-PEG-BSA Hydrogel: Design, Properties, and Multifunctional Functions

by Yuanyuan Qu, Jinlong Li, Xin Jia and Lijun Yin

J. Funct. Biomater. 2025, 16(2), 69; https://doi.org/10.3390/jfb16020069 - 18 Feb 2025

Cited by 1 | Viewed by 1419

Abstract

Hydrogel network structures play a crucial role in determining mechanical properties and have broad applications in biomedical and industrial fields. Therefore, their rational design is essential. Herein, we developed a Schiff base-crosslinked hydrogel through the reaction of Tetra-armed polyethylene glycol with aldehyde end [...] Read more.

Hydrogel network structures play a crucial role in determining mechanical properties and have broad applications in biomedical and industrial fields. Therefore, their rational design is essential. Herein, we developed a Schiff base-crosslinked hydrogel through the reaction of Tetra-armed polyethylene glycol with aldehyde end groups (Tetra-PEG-CHO) and bovine serum albumin (BSA) under alkaline conditions. In addition, the Tetra-PEG-BSA hydrogel showed a rapid gelation time of around 11 s, much faster than that of the GLU-BSA, HT-BSA, and GDL-BSA hydrogels. It had high optical transmittance (92.92% at 600 nm) and swelling ratios superior to the other gels in different solutions, maintaining structural integrity even in denaturing environments such as guanidine hydrochloride and SDS. Mechanical tests showed superior strain at break (84.12 ± 0.76%), rupture stress (28.64 ± 1.21 kPa), and energy dissipation ability (468.0 ± 34.9 kJ·m⁻³), surpassing all control group hydrogels. MTT cytotoxicity assays indicated that cell viability remained >80% at lower concentrations, confirming excellent biocompatibility. These findings suggest that Tetra-PEG-BSA hydrogels may serve as effective materials for drug delivery, tissue engineering, and 3D printing. Full article

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

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19 pages, 10575 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Bacterial Growth on Titanium Surfaces Treated with Nanosized Hydroxyapatite

by Maria Holmström, Sonia Esko, Karin Danielsson and Per Kjellin

J. Funct. Biomater. 2025, 16(2), 66; https://doi.org/10.3390/jfb16020066 - 16 Feb 2025

Viewed by 1029

Abstract

Bacterial growth on implant surfaces poses a significant obstacle to the long-term success of dental and orthopedic implants. There is a need for implants that promote osseointegration while at the same time decreasing or preventing bacterial growth. In this study, the existing methods [...] Read more.

Bacterial growth on implant surfaces poses a significant obstacle to the long-term success of dental and orthopedic implants. There is a need for implants that promote osseointegration while at the same time decreasing or preventing bacterial growth. In this study, the existing methods for the measurement of bacterial biofilms were adapted so that they were suitable for measuring the bacterial growth on implant surfaces. Two different strains of bacteria, Pseudomonas aeruginosa and Staphylococcus epidermidis, were used, and the in vitro effect of bacterial growth on titanium surfaces coated with an ultrathin (20–40 nm thick) layer of nanosized hydroxyapatite (nHA) was investigated. After 2 h of biofilm growth, there was a 33% reduction in both S. epidermidis and P. aeruginosa bacteria on nHA compared to Ti. For a more mature 24 h biofilm, there was a 46% reduction in S. epidermidis and a 43% reduction in P. aeruginosa on nHA compared to Ti. This shows that coating nHA onto implants could be of benefit in reducing implant-related infections. Full article

(This article belongs to the Special Issue Antibacterial Materials: Recent Advances in Methodologies and Regulations)

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13 pages, 2817 KiB

Open AccessEditor’s ChoiceArticle

Epigallocatechin-3-Gallate (EGCG)-Loaded Hyaluronic Acid Hydrogel Seems to Be Effective in a Rat Model of Collagenase-Induced Achilles Tendinopathy

by Hwa Jun Kang, Sivakumar Allur Subramanian, Si Young Song, Jihyun Hwang, Collin Lee and Sung Jae Kim

J. Funct. Biomater. 2025, 16(2), 55; https://doi.org/10.3390/jfb16020055 - 10 Feb 2025

Viewed by 1240

Abstract

Tendon injuries account for 45% of musculoskeletal injuries. However, research on the occurrence and pathogenesis of tendinopathy is insufficient, and there is still much debate regarding treatment methods. It is important to understand the molecular mechanisms of oxidative stress and inflammatory responses because [...] Read more.

Tendon injuries account for 45% of musculoskeletal injuries. However, research on the occurrence and pathogenesis of tendinopathy is insufficient, and there is still much debate regarding treatment methods. It is important to understand the molecular mechanisms of oxidative stress and inflammatory responses because oxidative stress in tendon tissue is induced by various factors, including inflammatory cytokines, drug exposure, and metabolic abnormalities. In this study, 28 rats were divided into four groups (7 rats assigned to each group): control group (CON), collagenase injection group (CL), collagenase injection and hyaluronic acid injection group (CL + HA), and collagenase injection and EGCG-loaded hyaluronic acid injection group (CL + HA + EGCG). Seven weeks after the start of the study, all rats underwent histochemical analysis, immunofluorescence staining, and Western blot. The results showed increased inflammatory cells, disarray of collagen matrix, and degradation of the collagen matrix in the CL group. However, in the EGCG-treated group, there was a significant increase in type I collagen expression and a significant decrease in type III collagen expression, compared to the CL group. Additionally, there was an increase in the expression of antioxidant markers SOD (Superoxide Dismutase) and CAT (Catalase), tenogenic markers COLL-1 (collagen type I), and SCX (Scleraxis), and a downregulated expression of apoptosis markers cas-3 and cas-7. Our findings suggest that EGCG-loaded hyaluronic acid hydrogel exhibits potential in preventing tendon damage and promoting the regeneration process in a rat model of Achilles tendinopathy. The insights gained from our histological and molecular investigations highlight the future potential for testing novel tendinopathy treatments in human subjects. Full article

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

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18 pages, 2192 KiB

Open AccessEditor’s ChoiceArticle

Next-Generation Biomaterials for Wound Healing: Development and Evaluation of Collagen Scaffolds Functionalized with a Heparan Sulfate Mimic and Fibroblast Growth Factor 2

by Merel Gansevoort, Sabine Wentholt, Gaia Li Vecchi, Marjolein de Vries, Elly M. M. Versteeg, Bouke K. H. L. Boekema, Agnes Choppin, Denis Barritault, Franck Chiappini, Toin H. van Kuppevelt and Willeke F. Daamen

J. Funct. Biomater. 2025, 16(2), 51; https://doi.org/10.3390/jfb16020051 - 7 Feb 2025

Cited by 1 | Viewed by 1745

Abstract

Fibrosis after full-thickness wound healing—especially after severe burn wounds—remains a clinically relevant problem. Biomaterials that mimic the lost dermal extracellular matrix have shown promise but cannot completely prevent scar formation. We present a novel approach where porous type I collagen scaffolds were covalently [...] Read more.

Fibrosis after full-thickness wound healing—especially after severe burn wounds—remains a clinically relevant problem. Biomaterials that mimic the lost dermal extracellular matrix have shown promise but cannot completely prevent scar formation. We present a novel approach where porous type I collagen scaffolds were covalently functionalized with ReGeneRating Agent (RGTA^®) OTR4120. RGTA^® is a glycanase-resistant heparan sulfate mimetic that promotes regeneration when applied topically to chronic wounds. OTR4120 is able to capture fibroblast growth factor 2 (FGF-2), a heparan/heparin-binding growth factor that inhibits the activity of fibrosis-driving myofibroblasts. Scaffolds with various concentrations and distributions of OTR4120 were produced. When loaded with FGF-2, collagen–OTR4120 scaffolds demonstrated sustained release of FGF-2 compared to collagen–heparin scaffolds. Their anti-fibrotic potential was investigated in vitro by seeding primary human dermal fibroblasts on the scaffolds followed by stimulation with transforming growth factor β1 (TGF-β1) to induce myofibroblast differentiation. Collagen–OTR4120(-FGF-2) scaffolds diminished the gene expression levels of several myofibroblast markers. In absence of FGF-2 the collagen–OTR4120 scaffolds displayed an inherent anti-fibrotic effect, as the expression of two fibrotic markers (TGF-β1 and type I collagen) was diminished. This work highlights the potential of collagen–OTR4120 scaffolds as biomaterials to improve skin wound healing. Full article

(This article belongs to the Special Issue Biomaterials for Wound Healing and Tissue Repair)

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38 pages, 3106 KiB

Open AccessEditor’s ChoiceReview

Exploring the Properties and Indications of Chairside CAD/CAM Materials in Restorative Dentistry

by Codruţa-Eliza Ille, Anca Jivănescu, Daniel Pop, Eniko Tunde Stoica, Razvan Flueras, Ioana-Cristina Talpoş-Niculescu, Raluca Mioara Cosoroabă, Ramona-Amina Popovici and Iustin Olariu

J. Funct. Biomater. 2025, 16(2), 46; https://doi.org/10.3390/jfb16020046 - 1 Feb 2025

Cited by 3 | Viewed by 2629

Abstract

The present review provides an up-to-date overview of chairside CAD/CAM materials used in restorative dentistry, focusing on their classification, properties, and clinical applications. If CAD/CAM technology was only an aspiration in the past, a higher proportion of clinics are employing it nowadays. The [...] Read more.

The present review provides an up-to-date overview of chairside CAD/CAM materials used in restorative dentistry, focusing on their classification, properties, and clinical applications. If CAD/CAM technology was only an aspiration in the past, a higher proportion of clinics are employing it nowadays. The market is overflowing with biomaterials, and these materials are constantly evolving, making it challenging for practitioners to choose the most appropriate one, especially in correlation with patients’ medical diseases. The evolution of CAD/CAM technology has revolutionized dental practice, enabling the efficient fabrication of high-quality restorations in a single appointment. The main categories of chairside CAD/CAM materials include feldspathic ceramics, leucite-reinforced ceramics, lithium disilicate, zirconia, hybrid ceramics, and acrylic resins. The mechanical, physical, and aesthetic properties of these materials are discussed, along with their advantages and limitations for different clinical scenarios. Factors influencing material selection, such as strength, aesthetics, and ease of use, are also assessed. Ultimately, the guiding principle of dentistry is minimally invasive treatment following the particularity of the clinical case to obtain the envisioned result. Correlating all these factors, a simple, up-to-date classification is required to begin an individualized treatment. By synthesizing current evidence, this comprehensive review aims to guide clinicians in selecting appropriate chairside CAD/CAM materials to achieve optimal functional and aesthetic outcomes in restorative procedures. The integration of digital workflows and continued development of novel materials promise to further enhance the capabilities of chairside CAD/CAM systems in modern dental practice. Full article

(This article belongs to the Special Issue State-of-the-Art Dental Adhesives and Restorative Composites)

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18 pages, 1206 KiB

Open AccessEditor’s ChoiceReview

Recent Advancements in Chitosan-Based Biomaterials for Wound Healing

by Jahnavi Shah, Dhruv Patel, Dnyaneshwari Rananavare, Dev Hudson, Maxwell Tran, Rene Schloss, Noshir Langrana, Francois Berthiaume and Suneel Kumar

J. Funct. Biomater. 2025, 16(2), 45; https://doi.org/10.3390/jfb16020045 - 30 Jan 2025

Cited by 7 | Viewed by 3435

Abstract

Chitosan is a positively charged natural polymer with several properties conducive to wound-healing applications, such as biodegradability, structural integrity, hydrophilicity, adhesiveness to tissue, and bacteriostatic potential. Along with other mechanical properties, some of the properties discussed in this review are antibacterial properties, mucoadhesive [...] Read more.

Chitosan is a positively charged natural polymer with several properties conducive to wound-healing applications, such as biodegradability, structural integrity, hydrophilicity, adhesiveness to tissue, and bacteriostatic potential. Along with other mechanical properties, some of the properties discussed in this review are antibacterial properties, mucoadhesive properties, biocompatibility, high fluid absorption capacity, and anti-inflammatory response. Chitosan forms stable complexes with oppositely charged polymers, arising from electrostatic interactions between (+) amino groups of chitosan and (−) groups of other polymers. These polyelectrolyte complexes (PECs) can be manufactured using various materials and methods, which brings a diversity of formulations and properties that can be optimized for specific wound healing as well as other applications. For example, chitosan-based PEC can be made into dressings/films, hydrogels, and membranes. There are various pros and cons associated with manufacturing the dressings; for instance, a layer-by-layer casting technique can optimize the nanoparticle release and affect the mechanical strength due to the formation of a heterostructure. Furthermore, chitosan’s molecular weight and degree of deacetylation, as well as the nature of the negatively charged biomaterial with which it is cross-linked, are major factors that govern the mechanical properties and biodegradation kinetics of the PEC dressing. The use of chitosan in wound care products is forecasted to drive the growth of the global chitosan market, which is expected to increase by approximately 14.3% within the next decade. This growth is driven by products such as chitoderm-containing ointments, which provide scaffolding for skin cell regeneration. Despite significant advancements, there remains a critical gap in translating chitosan-based biomaterials from research to clinical applications. Full article

(This article belongs to the Special Issue Functional Biomaterials for Skin Wound Healing)

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19 pages, 3130 KiB

Open AccessEditor’s ChoiceArticle

Development and Characterization of a Gelatin-Based Photoactive Hydrogel for Biomedical Application

by Antanas Straksys, Adei Abouhagger, Monika Kirsnytė-Šniokė, Tatjana Kavleiskaja, Arunas Stirke and Wanessa C. M. A. Melo

J. Funct. Biomater. 2025, 16(2), 43; https://doi.org/10.3390/jfb16020043 - 29 Jan 2025

Cited by 1 | Viewed by 1524

Abstract

Photoactive hydrogels facilitate light-triggered photochemical processes, positioning them as innovative solutions in biomedical applications, especially in antimicrobial photodynamic therapy. This study presents a novel methylene blue-based photoactive hydrogel designed as a topical gel solution to overcome the limitations of traditional pad-based systems by [...] Read more.

Photoactive hydrogels facilitate light-triggered photochemical processes, positioning them as innovative solutions in biomedical applications, especially in antimicrobial photodynamic therapy. This study presents a novel methylene blue-based photoactive hydrogel designed as a topical gel solution to overcome the limitations of traditional pad-based systems by offering enhanced adaptability to irregular wound surfaces, uniform photosensitizer distribution, and deeper therapeutic light penetration. This study investigated the development of hydrogels by cross-linking gelatin with glutaraldehyde (GA) and incorporating methylene blue (MB) to investigate the effects of cross-linking density, network structure, and small molecule inclusion on hydrogel properties. The results showed that while glutaraldehyde concentration influenced swelling behavior and network structure, the inclusion of MB altered these properties, particularly reducing swelling and MB retention at higher GA concentrations. Rheological and thermal analyses confirmed that higher GA concentrations made the hydrogels more rigid, with MB influencing both mechanical and thermal properties. Additionally, the hydrogels exhibited enhanced antimicrobial properties through increased reactive oxygen species production, particularly in light-activated conditions, demonstrating the potential of MB-based photoactive hydrogels for improving antimicrobial efficacy, especially against S. aureus, E. coli, and C. albicans, offering as a possible alternative to traditional antimicrobial treatments. Full article

(This article belongs to the Special Issue Functional Hydrogels for Drug Delivery Applications)

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14 pages, 2975 KiB

Open AccessEditor’s ChoiceArticle

Modulated-Diameter Zirconia Nanotubes for Controlled Drug Release—Bye to the Burst

by Gabriel Onyenso, Swathi Naidu Vakamulla Raghu, Patrick Hartwich and Manuela Sonja Killian

J. Funct. Biomater. 2025, 16(2), 37; https://doi.org/10.3390/jfb16020037 - 21 Jan 2025

Cited by 3 | Viewed by 2634

Abstract

The performance of an orthopedic procedure depends on several tandem functionalities. Such characteristics include materials’ surface properties and subsequent responses. Implant surfaces are typically roughened; this roughness can further be optimized to a specific morphology such as nanotubular roughness (ZrNTs) and the surfaces [...] Read more.

The performance of an orthopedic procedure depends on several tandem functionalities. Such characteristics include materials’ surface properties and subsequent responses. Implant surfaces are typically roughened; this roughness can further be optimized to a specific morphology such as nanotubular roughness (ZrNTs) and the surfaces can further be used as static drug reservoirs. ZrNTs coatings are attracting interest due to their potential to improve the success rate of implant systems, by means of better physical affixation and also micro/nano physio-chemical interaction with the extracellular matrix (ECM). Effective control over the drug release properties from such coatings has been the subject of several published reports. In this study, a novel and simple approach to extending drug release time and limiting the undesirable burst release from zirconia nanotubes (ZrNTs) via structural modification was demonstrated. The latter involved fabricating a double-layered structure with a modulated diameter and was achieved by varying the voltage and time during electrochemical anodization. The structurally modified ZrNTs and their homogenous equivalents were characterized via SEM and ToF-SIMS, and their drug release properties were monitored and compared using UV–Vis spectroscopy. We report a significant reduction in the initial burst release phenomenon and enhanced overall release time. The simple structural modification of ZrNTs can successfully enhance drug release performance, allowing for flexibility in designing drug delivery coatings for specific implant challenges, and offering a new horizon for smart biomaterials based on metal oxide nanostructures. Full article

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

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24 pages, 30692 KiB

Open AccessEditor’s ChoiceArticle

Sacrificing Alginate in Decellularized Extracellular Matrix Scaffolds for Implantable Artificial Livers

by Chanh-Trung Nguyen, Van Phu Le, Thi Huong Le, Jeong Sook Kim, Sung Hoon Back and Kyo-in Koo

J. Funct. Biomater. 2025, 16(1), 35; https://doi.org/10.3390/jfb16010035 - 19 Jan 2025

Viewed by 1979

Abstract

This research introduced a strategy to fabricate sub-millimeter-diameter artificial liver tissue by extruding a combination of a liver decellularized extracellular matrix (dECM), alginate, endothelial cells, and hepatocytes. Vascularization remains a critical challenge in liver tissue engineering, as replicating the liver’s intricate vascular network [...] Read more.

This research introduced a strategy to fabricate sub-millimeter-diameter artificial liver tissue by extruding a combination of a liver decellularized extracellular matrix (dECM), alginate, endothelial cells, and hepatocytes. Vascularization remains a critical challenge in liver tissue engineering, as replicating the liver’s intricate vascular network is essential for sustaining cellular function and viability. Seven scaffold groups were evaluated, incorporating different cell compositions, scaffold materials, and structural configurations. The hepatocyte and endothelial cell scaffold treated with alginate lyase demonstrated the highest diffusion rate, along with enhanced albumin secretion (2.8 µg/mL) and urea synthesis (220 µg/mL) during the same period by day 10. A dense and interconnected endothelial cell network was observed as early as day 4 in the lyased coculture group. Furthermore, three-week implantation studies in rats showed a stable integration to the host with no adverse effects. This approach offers significant potential for advancing functional liver tissue replacements, combining accelerated diffusion, enhanced albumin secretion, improved urea synthesis, dense vascular network formation, and stable implantation outcomes. Full article

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

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20 pages, 5255 KiB

Open AccessEditor’s ChoiceArticle

Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo Activity

by Thomas R. Fuerst, Alexander Marin, Sarah Jeong, Liudmila Kulakova, Raman Hlushko, Katrina Gorga, Eric A. Toth, Nevil J. Singh and Alexander K. Andrianov

J. Funct. Biomater. 2025, 16(1), 34; https://doi.org/10.3390/jfb16010034 - 19 Jan 2025

Cited by 1 | Viewed by 1681

Abstract

Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein [...] Read more.

Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies were characterized using dynamic light scattering and asymmetric flow field-flow fractionation methods and directly visualized in their vitrified state by cryogenic electron microscopy. The in vivo superiority of VMPNs over the individual components and an Alum-formulated vaccine manifests in higher neutralizing antibody titers, the promotion of a balanced IgG response, and the induction of a cellular immunity—CD4+ T cell responses to core proteins. The aqueous-based spontaneous co-assembly of antigens and immunopotentiating molecules enabled by a synthetic biodegradable carrier offers a simple and effective pathway to the development of polymer-based supramolecular nanovaccine systems. Full article

(This article belongs to the Special Issue Synthesis, Biomanufacturing, and Bio-Application of Advanced Polymers)

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20 pages, 4622 KiB

Open AccessEditor’s ChoiceArticle

Effects of Microstructured and Anti-Inflammatory-Coated Cochlear Implant Electrodes on Fibrous Tissue Growth and Neuronal Survival

by Lennart Fibranz, Wiebke Behrends, Katharina Wulf, Stefan Raggl, Lisa Kötter, Thomas Eickner, Soeren Schilp, Thomas Lenarz and Gerrit Paasche

J. Funct. Biomater. 2025, 16(1), 33; https://doi.org/10.3390/jfb16010033 - 18 Jan 2025

Viewed by 1287

Abstract

Cochlear implants are well established devices for treating severe hearing loss. However, due to the trauma caused by the insertion of the electrode and the subsequent formation of connective tissue, their clinical effectiveness varies. The aim of the current study was to achieve [...] Read more.

Cochlear implants are well established devices for treating severe hearing loss. However, due to the trauma caused by the insertion of the electrode and the subsequent formation of connective tissue, their clinical effectiveness varies. The aim of the current study was to achieve a long-term reduction in connective tissue growth and impedance by combining surface patterns on the electrode array with a poly-L-lactide coating containing 20% diclofenac. Three groups of six guinea pigs each (control, structure, structure with diclofenac in the coating) were implanted for four weeks. The hearing thresholds were measured before implantation and after 28 days, and impedances were monitored over time. After histological preparation, connective tissue growth and spiral ganglion neuron (SGN) survival were quantified. The hearing thresholds and impedances increased over time in all groups, showing no significant differences. The treatment groups showed increased damage in the cochlea, which appeared to be caused by the elevated parts of the microstructures. This seems to be amplified by the trauma model used in the current study. The impedances correlated with connective tissue growth near the electrode contacts. In addition, SGN survival was negatively correlated with the presence of connective tissue, both of which highlight the importance of successfully reducing connective tissue formation after cochlear implantation. Full article

(This article belongs to the Special Issue Recent Advances in Functional Coatings and Biomaterials Surfaces)

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17 pages, 8139 KiB

Open AccessEditor’s ChoiceArticle

Long-Term Stability and Osteogenic Activity of Recycled Polysulfone-Calcium Silicate Bone Implants In Vitro

by Chi-Nan Chang, Yun-Ru Huang and Shinn-Jyh Ding

J. Funct. Biomater. 2025, 16(1), 31; https://doi.org/10.3390/jfb16010031 - 17 Jan 2025

Cited by 1 | Viewed by 1073

Abstract

Environmental protection issues have received widespread attention, making material recycling increasingly important. The upcycling of polysulfone (PSF) medical waste, recognized as a high-performance plastic with excellent mechanical properties, deserves promotion. While PSF is suitable for use as an orthopedic implant material, such as [...] Read more.

Environmental protection issues have received widespread attention, making material recycling increasingly important. The upcycling of polysulfone (PSF) medical waste, recognized as a high-performance plastic with excellent mechanical properties, deserves promotion. While PSF is suitable for use as an orthopedic implant material, such as internal fixation, its osteogenesis capabilities must be enhanced. Mechanical stability, particularly over the long term, is a significant concern for bone implants in load-bearing applications. This study recycled PSF medical waste to create bone composites by incorporating osteogenic calcium silicate (CaSi) at three different contents: 10%, 20%, and 30%. We evaluated the phase, morphology, weight loss, and three-point bending strength of the PSF-based composites after they were soaked in dynamic simulated body fluid (SBF) at pH levels of 7.4 and 5.0 for up to 12 months. Human mesenchymal stem cells (hMSCs) were utilized to assess the osteogenic activity of these composites. Our findings revealed that, while the bending strength of PSF-based composites declined with prolonged exposure to SBF, the dissolution of CaSi particles led to a manageable weight loss of about 4% after 12 months, regardless of pH 7.4 or 5.0. Importantly, the incorporation of CaSi into the PSF matrix exhibited a positive effect on the attachment and proliferation of hMSCs. The levels of alkaline phosphatase (ALP) and calcium deposits directly correlated with the CaSi content, indicating superior osteogenic activity. Considering biostability and osteogenic ability, the 20% CaSi-PSF composite demonstrated promise as a candidate for load-bearing implant applications. Full article

(This article belongs to the Collection Feature Papers in Bone Biomaterials)

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13 pages, 12554 KiB

Open AccessEditor’s ChoiceArticle

Comparative In Vitro Study of Sol–Gel-Derived Bioactive Glasses Incorporated into Dentin Adhesives: Effects on Remineralization and Mechanical Properties of Dentin

by In-Seong Park, Hyun-Jung Kim, Jiyoung Kwon and Duck-Su Kim

J. Funct. Biomater. 2025, 16(1), 29; https://doi.org/10.3390/jfb16010029 - 16 Jan 2025

Viewed by 1604

Abstract

To overcome limitations of dentin bonding due to collagen degradation at a bonded interface, incorporating bioactive glass (BAG) into dentin adhesives has been proposed to enhance remineralization and improve bonding durability. This study evaluated sol–gel-derived BAGs (BAG79, BAG87, BAG91, and BAG79F) and conventional [...] Read more.

To overcome limitations of dentin bonding due to collagen degradation at a bonded interface, incorporating bioactive glass (BAG) into dentin adhesives has been proposed to enhance remineralization and improve bonding durability. This study evaluated sol–gel-derived BAGs (BAG79, BAG87, BAG91, and BAG79F) and conventional melt-quenched BAG (BAG45) incorporated into dentin adhesive to assess their remineralization and mechanical properties. The BAGs were characterized by using field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy for surface morphology. The surface area was measured by the Brunauer–Emmett–Teller method. X-ray diffraction (XRD) analysis was performed to determine the crystalline structure of the BAGs. Adhesive surface analysis was performed after approximating each experimental dentin adhesive and demineralized dentin by using FE-SEM. The elastic modulus of the treated dentin was measured after BAG-containing dentin adhesive application. The sol–gel-derived BAGs exhibited larger surface areas (by 400–600 times) than conventional BAG, with BAG87 displaying the largest surface area. XRD analysis indicated more pronounced and rapid formation of hydroxyapatite in the sol–gel BAGs. Dentin with BAG87-containing adhesive exhibited the highest elastic modulus. The incorporation of sol–gel-derived BAGs, especially BAG87, into dentin adhesives enhances the remineralization and mechanical properties of adhesive–dentin interfaces. Full article

(This article belongs to the Section Dental Biomaterials)

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38 pages, 3519 KiB

Open AccessEditor’s ChoiceReview

Biodegradable and Stimuli-Responsive Nanomaterials for Targeted Drug Delivery in Autoimmune Diseases

by Nargish Parvin, Sang Woo Joo and Tapas K. Mandal

J. Funct. Biomater. 2025, 16(1), 24; https://doi.org/10.3390/jfb16010024 - 14 Jan 2025

Cited by 9 | Viewed by 2584

Abstract

Autoimmune diseases present complex therapeutic challenges due to their chronic nature, systemic impact, and requirement for precise immunomodulation to avoid adverse side effects. Recent advancements in biodegradable and stimuli-responsive nanomaterials have opened new avenues for targeted drug delivery systems capable of addressing these [...] Read more.

Autoimmune diseases present complex therapeutic challenges due to their chronic nature, systemic impact, and requirement for precise immunomodulation to avoid adverse side effects. Recent advancements in biodegradable and stimuli-responsive nanomaterials have opened new avenues for targeted drug delivery systems capable of addressing these challenges. This review provides a comprehensive analysis of state-of-the-art biodegradable nanocarriers such as polymeric nanoparticles, liposomes, and hydrogels engineered for targeted delivery in autoimmune therapies. These nanomaterials are designed to degrade safely in the body while releasing therapeutic agents in response to specific stimuli, including pH, temperature, redox conditions, and enzymatic activity. By achieving localized and controlled release of anti-inflammatory and immunosuppressive agents, these systems minimize systemic toxicity and enhance therapeutic efficacy. We discuss the underlying mechanisms of stimuli-responsive nanomaterials, recent applications in treating diseases such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease, and the design considerations essential for clinical translation. Additionally, we address current challenges, including biocompatibility, scalability, and regulatory hurdles, as well as future directions for integrating advanced nanotechnology with personalized medicine in autoimmune treatment. This review highlights the transformative potential of biodegradable and stimuli-responsive nanomaterials, presenting them as a promising strategy to advance precision medicine and improve patient outcomes in autoimmune disease management. Full article

(This article belongs to the Special Issue Emerging Trends of Nanomaterials in Biology)

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15 pages, 5609 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Surface Functionalization of Magnesium Alloy on Degradability, Bioactivity, Cytotoxicity, and Antibiofilm Activity

by Morena Nocchetti, Michela Piccinini, Donatella Pietrella, Cinzia Antognelli, Maurizio Ricci, Alessandro Di Michele, Layla Jalaoui and Valeria Ambrogi

J. Funct. Biomater. 2025, 16(1), 22; https://doi.org/10.3390/jfb16010022 - 12 Jan 2025

Cited by 2 | Viewed by 1165

Abstract

Magnesium alloys are promising biomaterials to be used as temporary implants due to their biocompatibility and biodegradability. The main limitation in the use of these alloys is their rapid biodegradation. Moreover, the risk of microbial infections, often following the implant surgery and hard [...] Read more.

Magnesium alloys are promising biomaterials to be used as temporary implants due to their biocompatibility and biodegradability. The main limitation in the use of these alloys is their rapid biodegradation. Moreover, the risk of microbial infections, often following the implant surgery and hard to eradicate, is another challenge. Thus, with the aim of reducing biodegradability and conferring antibiofilm activity, sheets of the magnesium alloy AZ31 were properly modified with the introduction of hydroxy (polyethyleneoxy)propyl silane (PEG) and quaternary ammonium silane chains (QAS). The derivatized sheets were characterized by ATR-FTIR spectroscopy and their performances as concerns their stability, Mg²⁺ in vitro release, and in vitro bioactivity were evaluated as well. The results showed an increased stability with a reduction in corrosion, a slower Mg²⁺ ion release, and the formation of hydroxyapatite in the sheets’ surface. In addition, cytotoxicity evaluations were carried out on human gingival fibroblasts showing that the AZ31 and AZ31-PEG plates had good cytocompatibility. Finally, the antibiofilm activity on Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa was carried out by evaluating the capacity of inhibition of biofilm adhesion and formation. The results demonstrated a significant reduction in biofilm formation by Staphylococcus epidermidis on AZ31-QAS. Full article

(This article belongs to the Special Issue Advances in Biomedical Alloys and Surface Modification)

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23 pages, 3417 KiB

Open AccessEditor’s ChoiceReview

Natural Protein Films from Textile Waste for Wound Healing and Wound Dressing Applications

by Livia Ottaviano, Sara Buoso, Roberto Zamboni, Giovanna Sotgiu and Tamara Posati

J. Funct. Biomater. 2025, 16(1), 20; https://doi.org/10.3390/jfb16010020 - 10 Jan 2025

Cited by 3 | Viewed by 1887

Abstract

In recent years, several studies have focused on the development of sustainable, biocompatible, and biodegradable films with potential applications in wound healing and wound dressing systems. Natural macromolecules, particularly proteins, have emerged as attractive alternatives to synthetic polymers due to their biocompatibility, biodegradability, [...] Read more.

In recent years, several studies have focused on the development of sustainable, biocompatible, and biodegradable films with potential applications in wound healing and wound dressing systems. Natural macromolecules, particularly proteins, have emerged as attractive alternatives to synthetic polymers due to their biocompatibility, biodegradability, low immunogenicity, and adaptability. Among these proteins, keratin, extracted from waste wool, and fibroin, derived from Bombyx mori cocoons, exhibit exceptional properties such as mechanical strength, cell adhesion capabilities, and suitability for various fabrication methods. These proteins can also be functionalized with antimicrobial, antioxidant, and anti-inflammatory compounds, making them highly versatile for biomedical applications. This review highlights the promising potential of keratin- and fibroin-based films as innovative platforms for wound healing, emphasizing their advantages and the prospects they offer in creating next-generation wound dressing devices. Full article

(This article belongs to the Special Issue Natural Product-Based Biomaterials for Advanced Wound Dressings)

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16 pages, 7192 KiB

Open AccessEditor’s ChoiceArticle

Osteoblastic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells on P3HT Thin Polymer Film

by Paola Campione, Maria Giovanna Rizzo, Luana Vittoria Bauso, Ileana Ielo, Grazia Maria Lucia Messina and Giovanna Calabrese

J. Funct. Biomater. 2025, 16(1), 10; https://doi.org/10.3390/jfb16010010 - 2 Jan 2025

Cited by 1 | Viewed by 4100

Abstract

Bone defects restoration has always been an arduous challenge in the orthopedic field due to the limitations of conventional grafts. Bone tissue engineering offers an alternative approach by using biomimetic materials, stem cells, and growth factors that are able to improve the regeneration [...] Read more.

Bone defects restoration has always been an arduous challenge in the orthopedic field due to the limitations of conventional grafts. Bone tissue engineering offers an alternative approach by using biomimetic materials, stem cells, and growth factors that are able to improve the regeneration of bone tissue. Different biomaterials have attracted great interest in BTE applications, including the poly(3-hexylthiofene) (P3HT) conductive polymer, whose primary advantage is its capability to provide a native extracellular matrix-like environment. Based on this evidence, in this study, we evaluated the biological response of human adipose-derived mesenchymal stem cells cultured on P3HT thin polymer film for 14 days. Our results suggest that P3HT represents a good substrate to induce osteogenic differentiation of osteoprogenitor cells, even in the absence of specific inductive growth factors, thus representing a promising strategy for bone regenerative medicine. Therefore, the system provided may offer an innovative platform for next-generation biocompatible materials for regenerative medicine. Full article

(This article belongs to the Special Issue Mesoporous Nanomaterials for Bone Tissue Engineering)

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24 pages, 11240 KiB

Open AccessEditor’s ChoiceArticle

Study of the Interplay Among Melt Morphology, Rheology and 3D Printability of Poly(Lactic Acid)/Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate) Blends

by Marco Costantini, Flavio Cognini, Roberta Angelini, Sara Alfano, Marianna Villano, Andrea Martinelli, David Bolzonella, Marco Rossi and Andrea Barbetta

J. Funct. Biomater. 2025, 16(1), 9; https://doi.org/10.3390/jfb16010009 - 1 Jan 2025

Viewed by 1567

Abstract

Polymeric materials made from renewable sources that can biodegrade in the environment are attracting considerable attention as substitutes for petroleum-based polymers in many fields, including additive manufacturing and, in particular, Fused Deposition Modelling (FDM). Among the others, poly(hydroxyalkanoates) (PHAs) hold significant potential as [...] Read more.

Polymeric materials made from renewable sources that can biodegrade in the environment are attracting considerable attention as substitutes for petroleum-based polymers in many fields, including additive manufacturing and, in particular, Fused Deposition Modelling (FDM). Among the others, poly(hydroxyalkanoates) (PHAs) hold significant potential as candidates for FDM since they meet the sustainability and biodegradability standards mentioned above. However, the most utilised PHA, consisting of the poly(hydroxybutyrate) (PHB) homopolymer, has a high degree of crystallinity and low thermal stability near the melting point. As a result, its application in FDM has not yet attained mainstream adoption. Introducing a monomer with higher excluded volume, such as hydroxyvalerate, in the PHB primary structure, as in poly(hydroxybutyrate-co-valerate) (PHBV) copolymers, reduces the degree of crystallinity and the melting temperature, hence improving the PHA printability. Blending amorphous poly(lactic acid) (PLA) with PHBV enhances further PHA printability via FDM. In this work, we investigated the printability of two blends characterised by different PLA and PHBV weight ratios (25:75 and 50:50), revealing the close connection between blend microstructures, melt rheology and 3D printability. For instance, the relaxation time associated with die swelling upon extrusion determines the diameter of the extruded filament, while the viscoelastic properties the range of extrusion speed available. Through thoroughly screening printing parameters such as deposition speed, nozzle diameter, flow percentage and deposition platform temperature, we determined the optimal printing conditions for the two PLA/PHBV blends. It turned out that the blend with a 50:50 weight ratio could be printed faster and with higher accuracy. Such a conclusion was validated by replicating with remarkable fidelity high-complexity objects, such as a patient’s cancer-affected iliac crest model. Full article

(This article belongs to the Special Issue Advanced Technologies for Processing Functional Biomaterials)

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38 pages, 4157 KiB

Open AccessEditor’s ChoiceReview

Nano Delivery System for Atherosclerosis

by Zhuoyi Rong, Xuan He, Tianjian Fan and Haitao Zhang

J. Funct. Biomater. 2025, 16(1), 2; https://doi.org/10.3390/jfb16010002 - 24 Dec 2024

Cited by 2 | Viewed by 1939

Abstract

Atherosclerosis, a pathological process propelled by inflammatory mediators and lipids, is a principal contributor to cardiovascular disease incidents. Currently, drug therapy, the primary therapeutic strategy for atherosclerosis, faces challenges such as poor stability and significant side effects. The advent of nanomaterials has garnered [...] Read more.

Atherosclerosis, a pathological process propelled by inflammatory mediators and lipids, is a principal contributor to cardiovascular disease incidents. Currently, drug therapy, the primary therapeutic strategy for atherosclerosis, faces challenges such as poor stability and significant side effects. The advent of nanomaterials has garnered considerable attention from scientific researchers. Nanoparticles, such as liposomes and polymeric nanoparticles, have been developed for drug delivery in atherosclerosis treatment. This review will focus on how nanoparticles effectively improve drug safety and efficacy, as well as the continuous development and optimization of nanoparticles of the same material and further explore current challenges and future opportunities in this field. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Targeting and Drug Delivery)

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22 pages, 1557 KiB

Open AccessEditor’s ChoiceReview

Innovative Polymeric Biomaterials for Intraocular Lenses in Cataract Surgery

by Kevin Y. Wu, Rebecca Khammar, Hafsah Sheikh and Michael Marchand

J. Funct. Biomater. 2024, 15(12), 391; https://doi.org/10.3390/jfb15120391 - 23 Dec 2024

Viewed by 2808

Abstract

Intraocular lenses (IOLs) play a pivotal role in restoring vision following cataract surgery. The evolution of polymeric biomaterials has been central to addressing challenges such as biocompatibility, optical clarity, mechanical stability, and resistance to opacification. This review explores essential requirements for IOL biomaterials, [...] Read more.

Intraocular lenses (IOLs) play a pivotal role in restoring vision following cataract surgery. The evolution of polymeric biomaterials has been central to addressing challenges such as biocompatibility, optical clarity, mechanical stability, and resistance to opacification. This review explores essential requirements for IOL biomaterials, emphasizing their ability to mitigate complications like posterior capsule opacification (PCO) and dysphotopsias while maintaining long-term durability and visual quality. Traditional polymeric materials, including polymethyl methacrylate (PMMA), silicone, and acrylic polymers, are critically analyzed alongside cutting-edge innovations such as hydrogels, shape memory polymers, and light-adjustable lenses (LALs). Advances in polymer engineering have enabled these materials to achieve enhanced flexibility, transparency, and biocompatibility, driving their adoption in modern IOL design. Functionalization strategies, including surface modifications and drug-eluting designs, highlight advancements in preventing inflammation, infection, and other complications. The incorporation of UV-blocking and blue-light-filtering agents is also examined for their potential in reducing retinal damage. Furthermore, emerging technologies like nanotechnology and smart polymer-based biomaterials offer promising avenues for personalized, biocompatible IOLs with enhanced performance. Clinical outcomes, including visual acuity, contrast sensitivity, and patient satisfaction, are evaluated to provide an understanding of the current advancements and limitations in IOL development. We also discuss the current challenges and future directions, underscoring the need for cost-effective, innovative polymer-based solutions to optimize surgical outcomes and improve patients’ quality of life. Full article

(This article belongs to the Special Issue Polymers Materials Used in Biomedical Engineering)

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23 pages, 1894 KiB

Open AccessEditor’s ChoiceReview

3D Bioprinting in Limb Salvage Surgery

by Iosif-Aliodor Timofticiuc, Serban Dragosloveanu, Ana Caruntu, Andreea-Elena Scheau, Ioana Anca Badarau, Nicolae Dragos Garofil, Andreea Cristiana Didilescu, Constantin Caruntu and Cristian Scheau

J. Funct. Biomater. 2024, 15(12), 383; https://doi.org/10.3390/jfb15120383 - 19 Dec 2024

Cited by 6 | Viewed by 1720

Abstract

With the development of 3D bioprinting and the creation of innovative biocompatible materials, several new approaches have brought advantages to patients and surgical teams. Increasingly more bone defects are now treated using 3D-bioprinted prostheses and implementing new solutions relies on the ability of [...] Read more.

With the development of 3D bioprinting and the creation of innovative biocompatible materials, several new approaches have brought advantages to patients and surgical teams. Increasingly more bone defects are now treated using 3D-bioprinted prostheses and implementing new solutions relies on the ability of engineers and medical teams to identify methods of anchoring 3D-printed prostheses and to reveal the potential influence of bioactive materials on surrounding tissues. In this paper, we described why limb salvage surgery based on 3D bioprinting is a reliable and effective alternative to amputations, and why this approach is considered the new standard in modern medicine. The preliminary results of 3D bioprinting in one of the most challenging fields in surgery are promising for the future of machine-based medicine, but also for the possibility of replacing various parts from the human body with bioactive-based constructs. In addition, besides the materials and constructs that are already tested and applied in the human body, we also reviewed bioactive materials undergoing in vitro or in vivo testing with great potential for human applications in the near future. Also, we explored the recent advancements in clinically available 3D-bioprinted constructs and their relevance in this field. Full article

(This article belongs to the Special Issue Medical Application of Functional Biomaterials (2nd Edition))

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21 pages, 5285 KiB

Open AccessEditor’s ChoiceArticle

Three-Dimensional Printing of Hydrogel Blend Tissue Engineering Scaffolds with In Situ Delivery of Anticancer Drug for Treating Melanoma Resection-Induced Tissue Defects

by Xiao-Die Chen, Xin-Yang Zhang, Han-Qi Zhu, Helen H. Lu and Min Wang

J. Funct. Biomater. 2024, 15(12), 381; https://doi.org/10.3390/jfb15120381 - 18 Dec 2024

Cited by 1 | Viewed by 1602

Abstract

Surgery is considered the gold standard for treating melanoma, but the high recurrence rate after surgery still remains as a major challenge. Therefore, using doxorubicin (DOX) as a model drug, this study investigated the 3D printing of anticancer drug-loaded hydrogel blend scaffolds for [...] Read more.

Surgery is considered the gold standard for treating melanoma, but the high recurrence rate after surgery still remains as a major challenge. Therefore, using doxorubicin (DOX) as a model drug, this study investigated the 3D printing of anticancer drug-loaded hydrogel blend scaffolds for inhibiting post-operation melanoma recurrence and for promoting tissue regeneration. Three-dimensional printing could successfully produce methacrylate-modified chitosan (CSMA) and methylcellulose (MC) hydrogel blend scaffolds. Polymer blend inks exhibited satisfactory printability, and the printed porous scaffolds showed good biocompatibility and mechanical properties. Three-dimensionally printed DOX-loaded hydrogel scaffolds displayed controlled drug release, which may effectively prevent/impede tumor recurrence after surgery. Furthermore, combining 3D printing and bioprinting, DOX-loaded and rat bone marrow mesenchymal stem cell (rBMSC)-laden scaffolds were created for assessing local DOX delivery on healthy tissues. Within the 14-day culture period, rBMSCs encapsulated in multilayered scaffolds that were incorporated with DOX displayed rejuvenated cell viability. The 3D printed and bioprinted dual purpose hydrogel scaffolds have the promise of combating tumor recurrence and providing structural support for tissue regeneration. Full article

(This article belongs to the Special Issue Biomaterials and Porous Scaffolds for Tissue Engineering and Regenerative Medicine)

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18 pages, 2317 KiB

Open AccessEditor’s ChoiceArticle

Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System

by Hui Li, Junwei Liu, Jingru Wang, Zhuoyue Li, Jianming Yu, Xu Huang, Bingchuan Wan, Xiangbao Meng and Xuan Zhang

J. Funct. Biomater. 2024, 15(12), 372; https://doi.org/10.3390/jfb15120372 - 9 Dec 2024

Viewed by 1037

Abstract

Background: CY1-4, 9-nitropyridine [2′,3′:4,5] pyrimido [1,2-α] indole -5,11- dione, is an indoleamine 2,3-dioxygenase (IDO) inhibitor and a poorly water-soluble substance. It is very important to increase the solubility of CY1-4 to improve its bioavailability and therapeutic effect. In this study, the mesoporous silica [...] Read more.

Background: CY1-4, 9-nitropyridine [2′,3′:4,5] pyrimido [1,2-α] indole -5,11- dione, is an indoleamine 2,3-dioxygenase (IDO) inhibitor and a poorly water-soluble substance. It is very important to increase the solubility of CY1-4 to improve its bioavailability and therapeutic effect. In this study, the mesoporous silica nano-skeleton carrier material Sylysia was selected as the carrier to load CY1-4, and then the CY1-4 nano-skeleton drug delivery system (MSNM@CY1-4) was prepared by coating the hydrophilic polymer material Hydroxypropyl methylcellulose (HPMC) and the lipid material Distearoylphosphatidyl-ethanolamine-poly(ethylene glycol)₂₀₀₀ (DSPE-PEG₂₀₀₀) to improve the anti-tumor effect of CY1-4. Methods: The solubility and dissolution of MSNM@CY1-4 were investigated, and its bioavailability, anti-tumor efficacy, IDO inhibitory ability and immune mechanism were evaluated in vivo. Results: CY1-4 was loaded in MSNM@CY1-4 in an amorphous form, and MSNM@CY1-4 could significantly improve the solubility (up to about 200 times) and dissolution rate of CY1-4. In vivo studies showed that the oral bioavailability of CY1-4 in 20 mg/kg MSNM@CY1-4 was about 23.9-fold more than that in 50 mg/kg CY1-4 suspension. In B16F10 tumor-bearing mice, MSNM@CY1-4 significantly inhibited tumor growth, prolonged survival time, significantly inhibited IDO activity in blood and tumor tissues, and reduced Tregs in tumor tissues and tumor-draining lymph nodes to improve anti-tumor efficacy. Conclusions: The nano-skeleton drug delivery system (MSNM@CY1-4) constructed in this study is a potential drug delivery platform for improving the anti-tumor effect of oral poorly water-soluble CY1-4. Full article

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

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17 pages, 27303 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of the Degradation Properties of Plasma Electrolytically Oxidized Mg Alloy AZ31 Using Fluid Dynamic Accelerated Tests for Biodegradable Implants

by Muhammad Saqib, Kerstin Kremmer, Joerg Opitz, Michael Schneider and Natalia Beshchasna

J. Funct. Biomater. 2024, 15(12), 366; https://doi.org/10.3390/jfb15120366 - 3 Dec 2024

Cited by 2 | Viewed by 1278

Abstract

Magnesium alloys are promising biodegradable implant materials due to their excellent biocompatibility and non-toxicity. However, their poor corrosion resistance limits their application in vivo. Plasma electrolytic oxidation (PEO) is a powerful technique to improve the corrosion resistance of magnesium alloys. In this study, [...] Read more.

Magnesium alloys are promising biodegradable implant materials due to their excellent biocompatibility and non-toxicity. However, their poor corrosion resistance limits their application in vivo. Plasma electrolytic oxidation (PEO) is a powerful technique to improve the corrosion resistance of magnesium alloys. In this study, we present the accelerated degradation of PEO-treated AZ31 samples using a fluid dynamic test. The samples were prepared using different concentrations of KOH as an electrolyte along with NaSiO₃. The anodizing time and the biasing time were optimized to obtain the increased corrosion resistance. The analysis of the degraded samples using microscopy, SEM EDX measurements, and by calculating mass loss and corrosion rates showed a significant increase in the corrosion resistance after the polymer (Resomer© LG 855 S) coating was applied to the anodized samples. The results confirm (or convince) that PEO treatment is an effective way to improve the corrosion resistance of AZ31 magnesium alloy. The fluid dynamic test can be used as an accelerated degradation test for biodegradable alloys in simulated body fluids at a physiological temperature. The polymer coating further improves the corrosion resistance of the PEO-treated AZ31 samples. Full article

(This article belongs to the Special Issue Medical Application of Functional Biomaterials (2nd Edition))

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11 pages, 1834 KiB

Open AccessEditor’s ChoiceArticle

Photodynamic Therapy Using IR-783 Liposomes for Advanced Tongue and Breast Cancers in Humans

by Yasuo Komura, Shintarou Kimura, Yumi Hirasawa, Tomoko Katagiri, Ayana Takaura, Fumika Yoshida, Saki Fukuro, Hiromi Muranishi, Osamu Imataki and Koichiro Homma

J. Funct. Biomater. 2024, 15(12), 363; https://doi.org/10.3390/jfb15120363 - 2 Dec 2024

Viewed by 1698

Abstract

Photodynamic therapy (PDT) is a minimally invasive treatment that elicits tumor apoptosis using laser light exclusively applied to the tumor site. IR-783, a heptamethine cyanine (HMC) dye, impedes the proliferation of breast cancer cells, even without light. Although studies have investigated the efficacy [...] Read more.

Photodynamic therapy (PDT) is a minimally invasive treatment that elicits tumor apoptosis using laser light exclusively applied to the tumor site. IR-783, a heptamethine cyanine (HMC) dye, impedes the proliferation of breast cancer cells, even without light. Although studies have investigated the efficacy of IR-783 in cell and animal studies, its efficacy in clinical settings remains unknown. Therefore, we aimed to determine the efficacy of PDT using IR-783 liposomes. An HMC dye, excited by long-wavelength infrared light and with high tissue permeability, was used for PDT after liposomization to enhance tumor tissue accumulation. PDT was performed using IR-783 in two patients with either tongue or breast cancer, one each. IR-783 liposomes inhibited cell proliferation in tongue cancer cells even when not excited by light. Tumor size was markedly reduced in both cases, with no significant adverse events. Furthermore, the patient with tongue cancer exhibited improved respiratory, swallowing, and speech functions, which were attributed not only to the shrinkage of the tumor but also to the improvement in airway narrowing. In conclusion, PDT using IR-783 liposomes effectively reduces tumor size in tongue and breast cancers. Full article

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

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20 pages, 4201 KiB

Open AccessEditor’s ChoiceArticle

Impact of Particle Size and Sintering Temperature on Calcium Phosphate Gyroid Structure Scaffolds for Bone Tissue Engineering

by Romina Haydeé Aspera-Werz, Guanqiao Chen, Lea Schilonka, Islam Bouakaz, Catherine Bronne, Elisabeth Cobraiville, Grégory Nolens and Andreas Nussler

J. Funct. Biomater. 2024, 15(12), 355; https://doi.org/10.3390/jfb15120355 - 21 Nov 2024

Cited by 4 | Viewed by 1816

Abstract

Due to the chemical composition and structure of the target tissue, autologous bone grafting remains the gold standard for orthopedic applications worldwide. However, ongoing advancements in alternative grafting materials show that 3D-printed synthetic biomaterials offer many advantages. For instance, they provide high availability, [...] Read more.

Due to the chemical composition and structure of the target tissue, autologous bone grafting remains the gold standard for orthopedic applications worldwide. However, ongoing advancements in alternative grafting materials show that 3D-printed synthetic biomaterials offer many advantages. For instance, they provide high availability, have low clinical limitations, and can be designed with a chemical composition and structure comparable to the target tissue. This study aimed to compare the influences of particle size and sintering temperature on the mechanical properties and biocompatibility of calcium phosphate (CaP) gyroid scaffolds. CaP gyroid scaffolds were fabricated by 3D printing using powders with the same chemical composition but different particle sizes and sintering temperatures. The physicochemical characterization of the scaffolds was performed using X-ray diffractometry, scanning electron microscopy, and microtomography analyses. The immortalized human mesenchymal stem cell line SCP-1 (osteoblast-like cells) and osteoclast-like cells (THP-1 cells) were seeded on the scaffolds as mono- or co-cultures. Bone cell attachment, number of live cells, and functionality were assessed at different time points over a period of 21 days. Improvements in mechanical properties were observed for scaffolds fabricated with narrow-particle-size-distribution powder. The physicochemical analysis showed that the microstructure varied with sintering temperature and that narrow particle size distribution resulted in smaller micropores and a smoother surface. Viable osteoblast- and osteoclast-like cells were observed for all scaffolds tested, but scaffolds produced with a smaller particle size distribution showed less attachment of osteoblast-like cells. Interestingly, low attachment of osteoclast-like cells was observed for all scaffolds regardless of surface roughness. Although bone cell adhesion was lower in scaffolds made with powder containing smaller particle sizes, the long-term function of osteoblast-like and osteoclast-like cells was superior in scaffolds with improved mechanical properties. Full article

(This article belongs to the Special Issue Biomaterials and Porous Scaffolds for Tissue Engineering and Regenerative Medicine)

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14 pages, 6217 KiB

Open AccessEditor’s ChoiceArticle

The Effects of Surface Patterning and Photobiomodulation on the Osseointegration of Titanium Implants in Osteoporotic Long Bones: An In Vivo Study in Rats

by Theodor Popa, Mircea Negrutiu, Luciana Madalina Gherman, Alina Deniza Ciubean, Dan Ionut Cosma, Dan Gheban, Catalin Popa and Laszlo Irsay

J. Funct. Biomater. 2024, 15(11), 346; https://doi.org/10.3390/jfb15110346 - 14 Nov 2024

Viewed by 1317

Abstract

This study aimed to assess the impact of titanium surface patterning used in combination with photobiomodulation therapy on enhancing osseointegration in osteoporotic bone fractures. C.p. titanium implants were employed, half with an unmodified surface and half with a modified one, showing a nanostructured [...] Read more.

This study aimed to assess the impact of titanium surface patterning used in combination with photobiomodulation therapy on enhancing osseointegration in osteoporotic bone fractures. C.p. titanium implants were employed, half with an unmodified surface and half with a modified one, showing a nanostructured cellular surface. Surface patterning aimed to obtain a complex morphology designed for better osseointegration, using a selective anodization process after photoresist coating. A total of 52 rats were used, of which 4 were sacrificed 12 weeks after ovariectomy to evaluate bone density. A total of 48 rats received titanium implants in both tibiae and underwent surgery for implant placement and bone fracture. Half of the rats were subjected to photobiomodulation. The times of sacrifice were 2, 4, and 6 weeks after finalizing LASER therapy. The evaluation methods were micro-CT scanning, the mechanical pull-force test, and morphology. Mechanical tests revealed a significant difference in the surface-patterned titanium with the LASER group at 2 weeks, but not at 4 and 6 weeks. This group outperformed regular titanium and titanium/LASER groups. Micro-CT showed no significant differences, while the morphology indicated better bone quality at 4 weeks in all LASER-treated groups. The effect of surface patterning and photobiomodulation leads to better osseointegration, especially in the earlier stages. Full article

(This article belongs to the Special Issue Functional Composites for Bone Implants and Osseointegration)

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20 pages, 1556 KiB

Open AccessEditor’s ChoiceReview

Spheroid-Exosome-Based Bioprinting Technology in Regenerative Medicine

by Hwa-Yong Lee and Jin Woo Lee

J. Funct. Biomater. 2024, 15(11), 345; https://doi.org/10.3390/jfb15110345 - 14 Nov 2024

Cited by 1 | Viewed by 1752

Abstract

Since the discovery that exosomes can exchange genes, their potential use as tools for tissue regeneration, disease diagnosis, and therapeutic applications has drawn significant attention. Emerging three-dimensional (3D) printing technologies, such as bioprinting, which allows the printing of cells, proteins, DNA, and other [...] Read more.

Since the discovery that exosomes can exchange genes, their potential use as tools for tissue regeneration, disease diagnosis, and therapeutic applications has drawn significant attention. Emerging three-dimensional (3D) printing technologies, such as bioprinting, which allows the printing of cells, proteins, DNA, and other biological materials, have demonstrated the potential to create complex body tissues or personalized 3D models. The use of 3D spheroids in bioprinting facilitates volumetric tissue reconstruction and accelerates tissue regeneration via exosome secretion. In this review, we discussed a convergence approach between two promising technologies for bioprinting and exosomes in regenerative medicine. Among the various 3D cell culture methods used for exosome production, we focused on spheroids, which are suitable for mass production by bioprinting. We then summarized the research results on cases of bioprinting applications using the spheroids and exosomes produced. If a large number of spheroids can be supplied through bioprinting, the spheroid-exosome-based bioprinting technology will provide new possibilities for application in tissue regeneration, disease diagnosis, and treatment. Full article

(This article belongs to the Special Issue Advanced Technologies for Processing Functional Biomaterials)

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12 pages, 424 KiB

Open AccessEditor’s ChoiceSystematic Review

Propolis in Dental Implantology: A Systematic Review of Its Effects and Benefits

by Magdalena Sycińska-Dziarnowska, Liliana Szyszka-Sommerfeld, Magdalena Ziąbka, Krzysztof Woźniak and Gianrico Spagnuolo

J. Funct. Biomater. 2024, 15(11), 339; https://doi.org/10.3390/jfb15110339 - 12 Nov 2024

Cited by 1 | Viewed by 1677

Abstract

Dental implants are widely recognized for their effectiveness in restoring missing teeth, yet their success is often compromised by infections or inadequate osseointegration. Propolis, a natural resinous substance with potent antimicrobial, anti-inflammatory, and osteogenic properties, has emerged as a promising adjunct in dental [...] Read more.

Dental implants are widely recognized for their effectiveness in restoring missing teeth, yet their success is often compromised by infections or inadequate osseointegration. Propolis, a natural resinous substance with potent antimicrobial, anti-inflammatory, and osteogenic properties, has emerged as a promising adjunct in dental implantology. This systematic review critically evaluates the current evidence on the incorporation of propolis into dental implants, focusing on its impact on antimicrobial efficacy, bone healing, and overall implant stability. The study protocol was registered in PROSPERO under the registration number CRD42024577122. The PRISMA diagram visually represented the search strategy, screening, and inclusion process. Two reviewers conducted a comprehensive literature search across five databases: PubMed, PubMed Central, Embase, Scopus, and Web of Science. The review synthesized findings from 13 studies; in vitro, in vivo, and clinical studies, highlighting that propolis significantly enhances antibacterial and antifungal activities against pathogens such as Staphylococcus aureus, Candida albicans, and Streptococcus mutans, thereby reducing the risk of peri-implant infections. Additionally, propolis promotes osseointegration by stimulating osteoblast activity and reducing inflammatory cytokine expression, leading to improved bone formation and implant stability. The anti-inflammatory and antioxidant properties of propolis further contribute to a favorable healing environment, enhancing the long-term success of dental implants. The systematic review underscores the potential of propolis as a safe, biocompatible, and effective material for improving dental implant outcomes. However, it also identifies the need for more extensive clinical trials to fully establish standardized protocols for propolis application in implantology. This review provides an overview of propolis’s potential role in dental implants and suggests promising avenues for future research to optimize its benefits in clinical practice. Full article

(This article belongs to the Special Issue Biomaterials in Dentistry 2024)

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34 pages, 4136 KiB

Open AccessEditor’s ChoiceReview

Synthesis, Functionalization, and Biomedical Applications of Iron Oxide Nanoparticles (IONPs)

by Mostafa Salehirozveh, Parisa Dehghani and Ivan Mijakovic

J. Funct. Biomater. 2024, 15(11), 340; https://doi.org/10.3390/jfb15110340 - 12 Nov 2024

Cited by 10 | Viewed by 5644

Abstract

Iron oxide nanoparticles (IONPs) have garnered significant attention in biomedical applications due to their unique magnetic properties, biocompatibility, and versatility. This review comprehensively examines the synthesis methods, surface functionalization techniques, and diverse biomedical applications of IONPs. Various chemical and physical synthesis techniques, including [...] Read more.

Iron oxide nanoparticles (IONPs) have garnered significant attention in biomedical applications due to their unique magnetic properties, biocompatibility, and versatility. This review comprehensively examines the synthesis methods, surface functionalization techniques, and diverse biomedical applications of IONPs. Various chemical and physical synthesis techniques, including coprecipitation, sol–gel processes, thermal decomposition, hydrothermal synthesis, and sonochemical routes, are discussed in detail, highlighting their advantages and limitations. Surface functionalization strategies, such as ligand exchange, encapsulation, and silanization, are explored to enhance the biocompatibility and functionality of IONPs. Special emphasis is placed on the role of IONPs in biosensing technologies, where their magnetic and optical properties enable significant advancements, including in surface-enhanced Raman scattering (SERS)-based biosensors, fluorescence biosensors, and field-effect transistor (FET) biosensors. The review explores how IONPs enhance sensitivity and selectivity in detecting biomolecules, demonstrating their potential for point-of-care diagnostics. Additionally, biomedical applications such as magnetic resonance imaging (MRI), targeted drug delivery, tissue engineering, and stem cell tracking are discussed. The challenges and future perspectives in the clinical translation of IONPs are also addressed, emphasizing the need for further research to optimize their properties and ensure safety and efficacy in medical applications. This review aims to provide a comprehensive understanding of the current state and future potential of IONPs in both biosensing and broader biomedical fields. Full article

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

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11 pages, 2744 KiB

Open AccessEditor’s ChoiceArticle

Enhancing the Biological Properties of Organic–Inorganic Hybrid Calcium Silicate Cements: An In Vitro Study

by Minji Choi, Jiyoung Kwon, Ji-Hyun Jang, Duck-Su Kim and Hyun-Jung Kim

J. Funct. Biomater. 2024, 15(11), 337; https://doi.org/10.3390/jfb15110337 - 10 Nov 2024

Cited by 2 | Viewed by 1495

Abstract

(1) Background: This study aimed to enhance the biological properties of hydraulic calcium silicate cements (HCSCs) by incorporating organic and inorganic components, specifically elastin-like polypeptides (ELPs) and bioactive glass (BAG). We focused on the effects of these composites on the viability, migration, and [...] Read more.

(1) Background: This study aimed to enhance the biological properties of hydraulic calcium silicate cements (HCSCs) by incorporating organic and inorganic components, specifically elastin-like polypeptides (ELPs) and bioactive glass (BAG). We focused on the effects of these composites on the viability, migration, and osteogenic differentiation of human periodontal ligament fibroblasts (hPDLFs). (2) Methods: Proroot MTA was supplemented with 1–5 wt% 63S BAG and 10 wt% ELP. The experimental groups contained various combinations of HSCS with ELP and BAG. Cell viability was assessed using an MTT assay, cell migration was evaluated using wound healing and transwell assays, and osteogenic activity was determined through Alizarin Red S staining and a gene expression analysis of osteogenic markers (ALP, RUNX-2, OCN, and Col1A2). (3) Results: The combination of ELP and BAG significantly enhanced the viability of hPDLFs with an optimal BAG concentration of 1–4%. Cell migration assays demonstrated faster migration rates in groups with 2–4% BAG and ELP incorporation. Osteogenic activity was the highest with 2–3% BAG incorporation with ELP, as evidenced by intense Alizarin Red S staining and the upregulation of osteogenic differentiation markers. (4) Conclusions: The incorporation of ELP (organic) and BAG (inorganic) into HCSC significantly enhances the viability, migration, and osteogenic differentiation of hPDLFs. These findings suggest that composite HCSC might support healing in destructed bone lesions in endodontics. Full article

(This article belongs to the Special Issue Biomechanical Studies and Biomaterials in Dentistry)

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12 pages, 1338 KiB

Open AccessEditor’s ChoiceArticle

Bioactive Compounds Enhance the Biocompatibility and the Physical Properties of a Glass Ionomer Cement

by Aline Rogéria Freire de Castilho, Pedro Luiz Rosalen, Marina Yasbeck Oliveira, Jonny Burga-Sánchez, Simone Duarte, Ramiro Mendonça Murata and Regina Maria Puppin Rontani

J. Funct. Biomater. 2024, 15(11), 332; https://doi.org/10.3390/jfb15110332 - 7 Nov 2024

Cited by 1 | Viewed by 1582

Abstract

In order to characterize a novel restorative material, knowledge about the toxicological effect on human cells and the physical behavior of a glass ionomer cement (GIC) containing flavonoids was established. The flavonoids apigenin, naringenin, quercetin, and liquiritigenin were manually incorporated into a GIC. [...] Read more.

In order to characterize a novel restorative material, knowledge about the toxicological effect on human cells and the physical behavior of a glass ionomer cement (GIC) containing flavonoids was established. The flavonoids apigenin, naringenin, quercetin, and liquiritigenin were manually incorporated into a GIC. In the control group, no incorporation was performed. Two cell culture assays evaluated the toxicity of GICs: SRB and MTT. For both assays, the keratinocyte cell line (HaCaT) was exposed to GIC (n = 3/group) for 24 h. The physical properties of the GICs were evaluated by compressive strength (n = 10), surface roughness (n = 10), and hardness (n = 10) tests. Cell viability by SRB ranged from 103% to 97%. The control revealed a significant decrease in the metabolism of cells (61%) by MTT, while the GIC+apigenin slightly increased the succinic dehydrogenase activity (105%; p > 0.05), also confirmed microscopically. The compressive strength and roughness values were similar among groups, but the hardness increased after the incorporation of naringenin and quercetin into GIC (p < 0.05). The incorporation of flavonoids positively altered the biological and physical properties of the GICs. Full article

(This article belongs to the Section Dental Biomaterials)

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20 pages, 1856 KiB

Open AccessEditor’s ChoiceReview

Bioengineering the Junctional Epithelium in 3D Oral Mucosa Models

by Marianna Gavriiloglou, Mira Hammad, Jordan M. Iliopoulos, Pierre Layrolle and Danae A. Apatzidou

J. Funct. Biomater. 2024, 15(11), 330; https://doi.org/10.3390/jfb15110330 - 6 Nov 2024

Cited by 1 | Viewed by 2766

Abstract

Two-dimensional (2D) culture models and animal experiments have been widely used to study the pathogenesis of periodontal and peri-implant diseases and to test new treatment approaches. However, neither of them can reproduce the complexity of human periodontal tissues, making the development of a [...] Read more.

Two-dimensional (2D) culture models and animal experiments have been widely used to study the pathogenesis of periodontal and peri-implant diseases and to test new treatment approaches. However, neither of them can reproduce the complexity of human periodontal tissues, making the development of a successful 3D oral mucosal model a necessity. The soft-tissue attachment formed around a tooth or an implant function like a biologic seal, protecting the deeper tissues from bacterial infection. The aim of this review is to explore the advancements made so far in the biofabrication of a junctional epithelium around a tooth-like or an implant insert in vitro. This review focuses on the origin of cells and the variety of extracellular components and biomaterials that have been used for the biofabrication of 3D oral mucosa models. The existing 3D models recapitulate soft-tissue attachment around implant abutments and hydroxyapatite discs. Hereby, the qualitative and quantitative assessments performed for evidencing the soft-tissue attachment are critically reviewed. In perspective, the design of sophisticated 3D models should work together for oral immunology and microbiology biofilms to accurately reproduce periodontal and peri-implant diseases. Full article

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

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22 pages, 7402 KiB

Open AccessEditor’s ChoiceArticle

Development of Nanocomposite Microspheres for Nasal Administration of Deferiprone in Neurodegenerative Disorders

by Radka Boyuklieva, Plamen Katsarov, Plamen Zagorchev, Silviya Abarova, Asya Hristozova and Bissera Pilicheva

J. Funct. Biomater. 2024, 15(11), 329; https://doi.org/10.3390/jfb15110329 - 5 Nov 2024

Cited by 1 | Viewed by 1530

Abstract

Elevated brain iron levels are characteristic of many neurodegenerative diseases. As an iron chelator with short biological half-life, deferiprone leads to agranulocytosis and neutropenia with a prolonged therapeutic course. Its inclusion in sustained-release dosage forms may reduce the frequency of administration. On the [...] Read more.

Elevated brain iron levels are characteristic of many neurodegenerative diseases. As an iron chelator with short biological half-life, deferiprone leads to agranulocytosis and neutropenia with a prolonged therapeutic course. Its inclusion in sustained-release dosage forms may reduce the frequency of administration. On the other hand, when administered by an alternative route of administration, such as the nasal route, systemic exposure to deferiprone will be reduced, thereby reducing the occurrence of adverse effects. Direct nose-to-brain delivery has been raised as a non-invasive strategy to deliver drugs to the brain, bypassing the blood–brain barrier. The aim of the study was to develop and characterize nanocomposite microspheres suitable for intranasal administration by combining nano- and microparticle-based approaches. Nanoparticles with an average particle size of 213 ± 56 nm based on the biodegradable polymer poly-ε-caprolactone were developed using the solvent evaporation method. To ensure the deposition of the particles in the nasal cavity and avoid exhalation or deposition into the small airways, the nanoparticles were incorporated into composite structures of sodium alginate obtained by spray drying. Deferiprone demonstrated sustained release from the nanocomposite microspheres and high iron-chelating activity. Full article

(This article belongs to the Special Issue Medical Application of Functional Biomaterials (2nd Edition))

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12 pages, 4283 KiB

Open AccessEditor’s ChoiceArticle

Sonification of Deproteinized Bovine Bone Functionalized with Genistein Enhances Bone Repair in Peri-Implant Bone Defects in Ovariectomized Rats

by Nathália Dantas Duarte, Gabriel Mulinari-Santos, Fábio Roberto de Souza Batista, Marcelly Braga Gomes, Naara Gabriela Monteiro, Ana Cláudia Ervolino da Silva, Reinhard Gruber, Paulo Noronha Lisboa-Filho, Pedro Henrique Silva Gomes-Ferreira and Roberta Okamoto

J. Funct. Biomater. 2024, 15(11), 328; https://doi.org/10.3390/jfb15110328 - 5 Nov 2024

Cited by 3 | Viewed by 3034

Abstract

Estrogen deficiency is one of several contributing factors to catabolic changes in bone surrounding dental implants, impairing bone repair in defects requiring bone regeneration. Functionalizing bone substitutes is an alternative approach among various strategies to address this challenge. In this study, the aim [...] Read more.

Estrogen deficiency is one of several contributing factors to catabolic changes in bone surrounding dental implants, impairing bone repair in defects requiring bone regeneration. Functionalizing bone substitutes is an alternative approach among various strategies to address this challenge. In this study, the aim was to evaluate the effect of functionalizing deproteinized bovine bone (Bio-Oss^®, BO) with genistein via sonication on peri-implant bone defects in ovariectomized rats. The animals were randomly distributed according to the treatment into the following four groups (n = 10): BO sonicated with genistein (BOS + GEN), BO sonicated alone (BOS), untreated BO (BO), and blood clot only (CLOT). After twenty-eight days, implant removal torque was determined, and the peri-implant bone parameters were calculated based on computed microtomography. Additionally, the gene expression of bone turnover markers was evaluated. As a main result, the functionalization with genistein increased implant removal torque and the peri-implant bone volume in the BOS + GEN group compared to both BOS and BO groups (both p < 0.05). These findings suggest that the sonification of deproteinized bovine bone functionalized with genistein improves bone repair in peri-implant bone defects in ovariectomized rats. Full article

(This article belongs to the Special Issue Medical Application of Functional Biomaterials (2nd Edition))

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12 pages, 2475 KiB

Open AccessEditor’s ChoiceArticle

Calcium Phosphate Loaded with Curcumin Prodrug and Selenium Is Bifunctional in Osteosarcoma Treatments

by Mingjie Wang, Chunfeng Xu, Dong Xu, Chang Du and Yuelian Liu

J. Funct. Biomater. 2024, 15(11), 327; https://doi.org/10.3390/jfb15110327 - 3 Nov 2024

Viewed by 1627

Abstract

Although SeO₃²⁻ ions have been loaded onto calcium phosphate to treat a wide range of cancers, the quest to promote bone tissue regeneration is still ongoing. Curcumin (cur), an herbal extraction, can selectively inhibit tumor cells and promote osteogenesis. In this [...] Read more.

Although SeO₃²⁻ ions have been loaded onto calcium phosphate to treat a wide range of cancers, the quest to promote bone tissue regeneration is still ongoing. Curcumin (cur), an herbal extraction, can selectively inhibit tumor cells and promote osteogenesis. In this study, SeO₃²⁻ ions were co-precipitated in biomimetic calcium phosphate (Se@BioCaP), and modified curcumin prodrug (mcur) was adsorbed on diverse Se@BioCaP surfaces (mcur-Se@BioCaP-Ads). Co-precipitation yielded Se@BioCaP with a significantly higher Se content and exhibited a tailorable micro-/nanostructure. The favorable pH-responsive release of Se and mcur from mcur-Se@BioCaP-Ads showed a synergistic anticancer efficiency in OS cells, enhancing OS cell inhibition more than a single dose of them, which might be associated with ROS production in OS cells. In addition, increased alkaline phosphatase activity and calcium nodule formation in MC3T3-E1 pre-osteoblasts were also verified. These results suggest this novel mcur-Se@BioCaP-Ads has promising and widespread potential in OS treatments. Full article

(This article belongs to the Special Issue Mesoporous Nanomaterials for Bone Tissue Engineering)

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19 pages, 10730 KiB

Open AccessEditor’s ChoiceArticle

Mechanical and Corrosion Behaviour in Simulated Body Fluid of As-Fabricated 3D Porous L-PBF 316L Stainless Steel Structures for Biomedical Implants

by Pedro Nogueira, João Magrinho, Luis Reis, Augusto Moita de Deus, Maria Beatriz Silva, Pedro Lopes, Luís Oliveira, António Castela, Ricardo Cláudio, Jorge L. Alves, Maria Fátima Vaz, Maria Carmezim and Catarina Santos

J. Funct. Biomater. 2024, 15(10), 313; https://doi.org/10.3390/jfb15100313 - 21 Oct 2024

Cited by 2 | Viewed by 1895

Abstract

Laser powder bed fusion (L-PBF) is one of the most promising additive manufacturing technologies for creating customised 316L Stainless Steel (SS) implants with biomimetic characteristics, controlled porosity, and optimal structural and functional properties. However, the behaviour of as-fabricated 3D 316L SS structures without [...] Read more.

Laser powder bed fusion (L-PBF) is one of the most promising additive manufacturing technologies for creating customised 316L Stainless Steel (SS) implants with biomimetic characteristics, controlled porosity, and optimal structural and functional properties. However, the behaviour of as-fabricated 3D 316L SS structures without any surface finishing in environments that simulate body fluids remains largely unknown. To address this knowledge gap, the present study investigates the surface characteristics, the internal porosity, the corrosion in simulated body fluid (SBF), and the mechanical properties of as-fabricated 316L SS structures manufactured by L-PBF with rhombitruncated cuboctahedron (RTCO) unit cells with two distinct relative densities (10 and 35%). The microstructural analysis confirmed that the RTCO structure has a pure austenitic phase with a roughness of ~20 µm and a fine cellular morphology. The micro-CT revealed the presence of keyholes and a lack of fusion pores in both RTCO structures. Despite the difference in the internal porosity, the mechanical properties of both structures remain within the range of bone tissue and in line with the Gibson and Ashby model. Additionally, the as-fabricated RTCO structures demonstrated passive corrosion behaviour in the SBF solution. Thus, as-fabricated porous structures are promising biomaterials for implants due to their suitable surface roughness, mechanical properties, and corrosion resistance, facilitating bone tissue growth. Full article

(This article belongs to the Section Bone Biomaterials)

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17 pages, 6847 KiB

Open AccessEditor’s ChoiceArticle

PLLA/GO Scaffolds Filled with Canine Placenta Hydrogel and Mesenchymal Stem Cells for Bone Repair in Goat Mandibles

by Thamires Santos-Silva, Inácio Silva Viana, Andrea Barros Piazzon S. Queiroz, Fabrício Singaretti de Oliveira, Bianca de Oliveira Horvath-Pereira, Leandro Norberto da Silva-Júnior, Michelle Silva Araujo, Paulo Alescio Canola, Luís Gustavo Gosuen G. Dias, Marcelo Melo Soares and Maria Angelica Miglino

J. Funct. Biomater. 2024, 15(10), 311; https://doi.org/10.3390/jfb15100311 - 20 Oct 2024

Cited by 2 | Viewed by 1740

Abstract

Bone defects in animals can arise from various causes, including diseases, neoplasms, and most commonly, trauma. Comminuted fractures that exceed the critical size may heal poorly due to deficient or interrupted vascularization, resulting in an insufficient number of progenitor cells necessary for bone [...] Read more.

Bone defects in animals can arise from various causes, including diseases, neoplasms, and most commonly, trauma. Comminuted fractures that exceed the critical size may heal poorly due to deficient or interrupted vascularization, resulting in an insufficient number of progenitor cells necessary for bone regeneration. In this context, 3D printing techniques using poly-L-lactic acid/graphene oxide (PLLA/GO) aim to address this issue by creating customized scaffolds combined with canine placenta hydrogel and mesenchymal stem cells for use in goat mandibles, compared to a control group using titanium plate fixation. Ten canine placentas were decellularized and characterized using histological techniques. A hydrogel derived from the canine placenta extracellular matrix (cpECM) was produced to improve cell attachment to the scaffolds. In vitro cytotoxicity and cell adhesion to the cpECM hydrogel were assessed by scanning electron microscopy (SEM). The resulting biomaterials, cpECM hydrogel and PLLA/GO scaffolds, maintained their functional structure and supported cell adhesion, maintenance, and proliferation in vitro. Thermography showed that PLLA/GO scaffolds with cpECM hydrogel performed effectively, similar to the control group. Computed tomography scans revealed bone calluses, suggesting an ongoing repair process. These findings demonstrate the innovative technological potential of these materials for use in surgical interventions. Future studies on PLLA/GO scaffolds will provide further insights into their effects on goat models. Full article

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

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16 pages, 5120 KiB

Open AccessEditor’s ChoiceArticle

A Polyurethane Electrospun Membrane Loaded with Bismuth Lipophilic Nanoparticles (BisBAL NPs): Proliferation, Bactericidal, and Antitumor Properties, and Effects on MRSA and Human Breast Cancer Cells

by Jesús Alejandro Torres-Betancourt, Rene Hernández-Delgadillo, Juan Valerio Cauich-Rodríguez, Diego Adrián Oliva-Rico, Juan Manuel Solis-Soto, Claudia María García-Cuellar, Yesennia Sánchez-Pérez, Nayely Pineda-Aguilar, Samantha Flores-Treviño, Irene Meester, Sergio Eduardo Nakagoshi-Cepeda, Katiushka Arevalo-Niño, María Argelia Akemi Nakagoshi-Cepeda and Claudio Cabral-Romero

J. Funct. Biomater. 2024, 15(10), 309; https://doi.org/10.3390/jfb15100309 - 16 Oct 2024

Cited by 1 | Viewed by 1520

Abstract

Electrospun membranes (EMs) have a wide range of applications, including use as local delivery systems. In this study, we manufactured a polyurethane Tecoflex™ EM loaded with bismuth-based lipophilic nanoparticles (Tecoflex™ EMs-BisBAL NPs). The physicochemical and mechanical characteristics, along with the antitumor and bactericidal [...] Read more.

Electrospun membranes (EMs) have a wide range of applications, including use as local delivery systems. In this study, we manufactured a polyurethane Tecoflex™ EM loaded with bismuth-based lipophilic nanoparticles (Tecoflex™ EMs-BisBAL NPs). The physicochemical and mechanical characteristics, along with the antitumor and bactericidal effects, were evaluated using a breast cancer cell line and methicillin-susceptible and resistant Staphylococcus aureus (MRSA). Drug-free Tecoflex™ EMs and Tecoflex™ EMs-BisBAL NPs had similar fiber diameters of 4.65 ± 1.42 µm and 3.95 ± 1.32 µm, respectively. Drug-free Tecoflex™ EMs did not negatively impact a human fibroblast culture, indicating that the vehicle is biocompatible. Tecoflex™ EMs-BisBAL NPs increased 94% more in size than drug-free Tecoflex™ EMs, indicating that the BisBAL NPs enhanced hydration capacity. Tecoflex™ EMs-BisBAL NPs were highly bactericidal against both methicillin-susceptible S. aureus and MRSA clinical isolates, inhibiting their growth by 93.11% and 61.70%, respectively. Additionally, Tecoflex™ EMs-BisBAL NPs decreased the viability of MCF-7 tumor cells by 86% after 24 h exposure and 70.1% within 15 min. Regarding the mechanism of action of Tecoflex™ EMs-BisBAL NPs, it appears to disrupt the tumor cell membrane. In conclusion, Tecoflex™ EMs-BisBAL NPs constitute an innovative low-cost drug delivery system for human breast cancer and postoperative wound infections. Full article

(This article belongs to the Special Issue Active Biomedical Materials and Their Applications, 2nd Edition)

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14 pages, 3923 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial Activity of Amino-Modified Cellulose Nanofibrils Decorated with Silver Nanoparticles

by Vesna Lazić, Jovan M. Nedeljković and Vanja Kokol

J. Funct. Biomater. 2024, 15(10), 304; https://doi.org/10.3390/jfb15100304 - 13 Oct 2024

Cited by 1 | Viewed by 1540

Abstract

Silver nanoparticles (Ag NPs) conjugated with amino-functionalized cellulose nanofibrils (NH₂−CNFs) were in situ-prepared by reducing silver ions with free amino groups from NH₂−CNFs. The spectroscopy and transmission electron microscopy measurements confirmed the presence of non-agglomerated nanometer-in-size Ag NPs within [...] Read more.

Silver nanoparticles (Ag NPs) conjugated with amino-functionalized cellulose nanofibrils (NH₂−CNFs) were in situ-prepared by reducing silver ions with free amino groups from NH₂−CNFs. The spectroscopy and transmission electron microscopy measurements confirmed the presence of non-agglomerated nanometer-in-size Ag NPs within micrometer-large NH₂−CNFs of high (20 wt.-%) content. Although the consumption of amino groups during the formation of Ag NPs lowers the ζ-potential and surface charge of prepared inorganic–organic hybrids (from +31.3 to +19.9 mV and from 2.4 to 1.0 mmol/g at pH 7, respectively), their values are sufficiently positive to ensure electrostatic interaction with negatively charged cell walls of pathogens in acidic and slightly (up to pH ~8.5) alkaline solutions. The antimicrobial activity of hybrid microparticles against various pathogens (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans) is comparable with pristine NH₂−CNFs. However, a long-timescale use of hybrids ensures the slow and controlled release of Ag⁺ ions to surrounding media (less than 1.0 wt.-% for one month). Full article

(This article belongs to the Special Issue Nanostructured Materials/Biomaterials for Healthcare Applications)

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15 pages, 3373 KiB

Open AccessEditor’s ChoiceArticle

Osteoblast Response to Widely Ranged Texturing Conditions Obtained through High Power Laser Beams on Ti Surfaces

by Federico Alessandro Ruffinatti, Tullio Genova, Ilaria Roato, Martina Perin, Giorgia Chinigò, Riccardo Pedraza, Olivio Della Bella, Francesca Motta, Elisa Aimo Boot, Domenico D’Angelo, Giorgio Gatti, Giorgia Scarpellino, Luca Munaron and Federico Mussano

J. Funct. Biomater. 2024, 15(10), 303; https://doi.org/10.3390/jfb15100303 - 12 Oct 2024

Viewed by 1525

Abstract

Titanium and titanium alloys are the prevailing dental implant materials owing to their favorable mechanical properties and biocompatibility, but how roughness dictates the biological response is still a matter of debate. In this study, laser texturing was used to generate eight paradigmatic roughened [...] Read more.

Titanium and titanium alloys are the prevailing dental implant materials owing to their favorable mechanical properties and biocompatibility, but how roughness dictates the biological response is still a matter of debate. In this study, laser texturing was used to generate eight paradigmatic roughened surfaces, with the aim of studying the early biological response elicited on MC3T3-E1 pre-osteoblasts. Prior to cell tests, the samples underwent SEM analysis, optical profilometry, protein adsorption assay, and optical contact angle measurement with water and diiodomethane to determine surface free energy. While all the specimens proved to be biocompatible, supporting similar cell viability at 1, 2, and 3 days, surface roughness could impact significantly on cell adhesion. Factorial analysis and linear regression showed, in a robust and unprecedented way, that an isotropic distribution of deep and closely spaced valleys provides the best condition for cell adhesion, to which both protein adsorption and surface free energy were highly correlated. Overall, here the authors provide, for the first time, a thorough investigation of the relationship between roughness parameters and osteoblast adhesion that may be applied to design and produce new tailored interfaces for implant materials. Full article

(This article belongs to the Special Issue Advanced Biomaterials and Biotechnology: Applications in Dental Medicine—2nd Edition)

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20 pages, 8915 KiB

Open AccessEditor’s ChoiceArticle

Bioconjugation of Serratiopeptidase with Titanium Oxide Nanoparticles: Improving Stability and Antibacterial Properties

by Jhon Jairo Melchor-Moncada, Santiago Vasquez-Giraldo, Augusto Zuluaga-Vélez, Lina Marcela Orozco, Luz Angela Veloza and Juan Carlos Sepúlveda-Arias

J. Funct. Biomater. 2024, 15(10), 300; https://doi.org/10.3390/jfb15100300 - 7 Oct 2024

Cited by 3 | Viewed by 2078

Abstract

Antimicrobial resistance (AMR) poses a significant global health threat, necessitating the development of novel antibacterial strategies. Serratiopeptidase (SP), a metalloprotease produced by bacteria such as Serratia marcescens, has gained attention not only for its anti-inflammatory properties but also for its potential antibacterial [...] Read more.

Antimicrobial resistance (AMR) poses a significant global health threat, necessitating the development of novel antibacterial strategies. Serratiopeptidase (SP), a metalloprotease produced by bacteria such as Serratia marcescens, has gained attention not only for its anti-inflammatory properties but also for its potential antibacterial activity. However, its protein nature makes it susceptible to pH changes and self-proteolysis, limiting its effectiveness. This study aimed to increase both the enzymatic stability and antibacterial activity of serratiopeptidase through immobilization on titanium oxide nanoparticles (TiO₂-NPs), leveraging the biocompatibility and stability of these nanomaterials. Commercial TiO₂-NPs were characterized using TGA/DTG, FT-IR, UV–Vis, and XRD analyses, and their biocompatibility was assessed through cytotoxicity studies. Serratiopeptidase was produced via fermentation using the C8 isolate of Serratia marcescens obtained from the intestine of Bombyx mori L., purified chromatographically, and immobilized on carboxylated nanoparticles via EDC/NHS coupling at various pH conditions. The optimal enzymatic activity was achieved by using pH 5.1 for nanoparticle activation and pH 5.5 for enzyme coupling. The resulting bioconjugate demonstrated stable proteolytic activity at 25 °C for 48 h. Immobilization was confirmed by FT-IR spectroscopy, and the Michaelis–Menten kinetics were determined. Notably, the bioconjugate exhibited two-fold greater antibacterial activity against E. coli than the free enzyme or TiO₂-NPs at 1000 µg/mL. This study successfully developed a serratiopeptidase–TiO₂ bioconjugate with enhanced enzymatic stability and antibacterial properties. The improved antibacterial activity of the immobilized enzyme presents a promising approach for developing new tools to combat antimicrobial resistance, with potential applications in healthcare, food safety, and environmental protection. Full article

(This article belongs to the Special Issue Medical Application of Functional Biomaterials (2nd Edition))

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17 pages, 6452 KiB

Open AccessEditor’s ChoiceArticle

3D-Printable Gelatin Methacrylate-Xanthan Gum Hydrogel Bioink Enabling Human Induced Pluripotent Stem Cell Differentiation into Cardiomyocytes

by Virginia Deidda, Isabel Ventisette, Marianna Langione, Lucrezia Giammarino, Josè Manuel Pioner, Caterina Credi and Federico Carpi

J. Funct. Biomater. 2024, 15(10), 297; https://doi.org/10.3390/jfb15100297 - 5 Oct 2024

Cited by 3 | Viewed by 2448

Abstract

We describe the development of a bioink to bioprint human induced pluripotent stem cells (hiPSCs) for possible cardiac tissue engineering using a gelatin methacrylate (GelMA)-based hydrogel. While previous studies have shown that GelMA at a low concentration (5% w/v) allows [...] Read more.

We describe the development of a bioink to bioprint human induced pluripotent stem cells (hiPSCs) for possible cardiac tissue engineering using a gelatin methacrylate (GelMA)-based hydrogel. While previous studies have shown that GelMA at a low concentration (5% w/v) allows for the growth of diverse cells, its 3D printability has been found to be limited by its low viscosity. To overcome that drawback, making the hydrogel both compatible with hiPSCs and 3D-printable, we developed an extrudable GelMA-based bioink by adding xanthan gum (XG). The GelMA-XG composite hydrogel had an elastic modulus (~9 kPa) comparable to that of cardiac tissue, and enabled 3D printing with high values of printing accuracy (83%) and printability (0.98). Tests with hiPSCs showed the hydrogel’s ability to promote their proliferation within both 2D and 3D cell cultures. The tests also showed that hiPSCs inside hemispheres of the hydrogel were able to differentiate into cardiomyocytes, capable of spontaneous contractions (average frequency of ~0.5 Hz and amplitude of ~2%). Furthermore, bioprinting tests proved the possibility of fabricating 3D constructs of the hiPSC-laden hydrogel, with well-defined line widths (~800 μm). Full article

(This article belongs to the Special Issue State of the Art: Three-Dimensional Printing Materials and Regenerative Medicine)

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