Journal of Functional Biomaterials

18 pages, 2565 KiB

Open AccessArticle

Six-Year Implants Follow-Up After Guided Bone Regeneration Using Autologous Tooth Graft: Innovative Biomaterial for Bone Regeneration Tooth Transformer^®

by Elio Minetti, Angelo Michele Inchingolo, Laura Ferrante, Grazia Marinelli, Francesco Inchingolo, Alessio Danilo Inchingolo, Andrea Palermo and Gianna Dipalma

J. Funct. Biomater. 2025, 16(5), 172; https://doi.org/10.3390/jfb16050172 - 9 May 2025

Abstract

Objectives: Recently, there has been great interest in teeth and their derivatives as suitable substrates for the treatment of alveolar bone defects. This retrospective study evaluates the clinical and radiographic outcomes of implants inserted in a site that underwent GBR procedure using a [...] Read more.

Objectives: Recently, there has been great interest in teeth and their derivatives as suitable substrates for the treatment of alveolar bone defects. This retrospective study evaluates the clinical and radiographic outcomes of implants inserted in a site that underwent GBR procedure using a tooth derivate material. Materials and methods: A total of 21 patients received a GBR using an autologous extracted tooth. Four months after the GBR techniques, the implants were inserted and were followed for an average of 5.28 + −1.10 years after loading. The X-ray was analyzed after a period of 63.36 + −13.2 months for a total follow-up period. Results: A total of 28 implants were inserted. All the implants were clinically functional after the follow-up period. The average bone loss from the X-ray images was 0.1208 + −0.1307. Conclusion: Within the limitations of this study, the use of a tooth as a graft using a tooth transformer device guarantees the production of bone and maintenance over time. Full article

(This article belongs to the Special Issue Application of Biomaterials and Techniques in Dental Surgical Treatment (2nd Edition))

► Show Figures

Figure 1

2 pages, 2188 KiB

Open AccessCorrection

Correction: Al Madhoun et al. Randomized Clinical Trial: Bone Bioactive Liquid Improves Implant Stability and Osseointegration. J. Funct. Biomater. 2024, 15, 293

by Ashraf Al Madhoun, Khaled Meshal, Neus Carrió, Eduard Ferrés-Amat, Elvira Ferrés-Amat, Miguel Barajas, Ana Leticia Jiménez-Escobar, Areej Said Al-Madhoun, Alaa Saber, Yazan Abou Alsamen, Carles Marti and Maher Atari

J. Funct. Biomater. 2025, 16(5), 171; https://doi.org/10.3390/jfb16050171 - 9 May 2025

Abstract

Error in Figure and Figure Legend [...] Full article

(This article belongs to the Section Dental Biomaterials)

► Show Figures

Figure 3

17 pages, 23065 KiB

Open AccessArticle

The Influence of Ca on Mechanical Properties of the Mg–Ca–Zn–RE–Zr Alloy for Orthopedic Applications

by Mircea Cătălin Ivănescu, Corneliu Munteanu, Ramona Cimpoeșu, Bogdan Istrate, Fabian Cezar Lupu, Marcelin Benchea, Eusebiu Viorel Șindilar, Alexandru Vlasa, Ovidiu Stamatin and Georgeta Zegan

J. Funct. Biomater. 2025, 16(5), 170; https://doi.org/10.3390/jfb16050170 - 9 May 2025

Abstract

Background: This study examined how the concentration of calcium (Ca) influences the microstructure, mechanical characteristics, and tribological attributes of Mg–Ca–Zn–RE–Zr alloys for orthopedic medicine. Materials and methods: Experimental alloys with 0.1 and 0.5 wt% Ca were prepared in a controlled atmosphere induction furnace. [...] Read more.

Background: This study examined how the concentration of calcium (Ca) influences the microstructure, mechanical characteristics, and tribological attributes of Mg–Ca–Zn–RE–Zr alloys for orthopedic medicine. Materials and methods: Experimental alloys with 0.1 and 0.5 wt% Ca were prepared in a controlled atmosphere induction furnace. The microstructure of the alloys was investigated by scanning electron microscopy, the chemical composition by X-ray fluorescence and energy-dispersive spectroscopy, the mechanical properties by indentation and scratching, and the corrosion resistance by linear and cyclic potentiometry. Results: The alloy with 0.1% Ca exhibited greater fluctuations in the coefficient of friction, while the sample with 0.5% Ca showed a higher susceptibility to cracking. Regarding corrosion resistance, both samples exhibited a generalized corrosion trend with similar corrosion currents. At lower Ca concentrations (0.1%), the refined microstructure of the alloys provided an elastic modulus closer to that of human bone, minimizing the risk of excessive local stress and promoting uniform load distribution at the bone-implant interface. Conclusion: The 0.5% Ca alloy offered superior tribological stability and better shock absorption, making it suitable for applications requiring long-term stability. The study highlighted the potential of both compositions based on the specific requirements of biodegradable orthopedic implants. Full article

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

► Show Figures

Figure 1

18 pages, 1215 KiB

Open AccessArticle

Evaluation of the Genotoxicity and Cytotoxicity of Bioceramic Endodontic Sealers in HepG2 and V79 Cell Lines: An In Vitro Study Using the Comet and Micronucleus Assays

by Antonija Tadin, Marija Badrov, Danijela Juric Kacunic, Nada Galic, Matea Macan, Ivan Kovacic and Davor Zeljezic

J. Funct. Biomater. 2025, 16(5), 169; https://doi.org/10.3390/jfb16050169 - 9 May 2025

Abstract

Background: The primary objective of this study was to evaluate the cytotoxic and genotoxic effects of calcium silicate-based sealers (BioRoot RCS and MTA Fillapex) compared to an epoxy-based sealer (AH Plus). Materials and methods: The study was conducted in vitro with the cell [...] Read more.

Background: The primary objective of this study was to evaluate the cytotoxic and genotoxic effects of calcium silicate-based sealers (BioRoot RCS and MTA Fillapex) compared to an epoxy-based sealer (AH Plus). Materials and methods: The study was conducted in vitro with the cell lines HepG2 and V79 to evaluate cytotoxicity and genotoxicity using the comet and micronucleus assays. Eluates of the materials were tested at two different concentrations (3 cm²/mL and 0.5 cm²/mL) after an exposure time of 72 h. Data were analyzed using the Mann–Whitney and Kruskal–Wallis tests (p < 0.05). Results: At lower concentrations in both cell lines, MTA Fillapex showed no significant difference in the measured comet assay parameters compared to the negative control (p > 0.05). In addition, it showed significantly lower genotoxic effects compared to AH Plus for all comet assay parameters, concentrations, and cell lines (p ≤ 0.001). BioRoot RCS showed lower primary DNA damage (p ≤ 0.001) than AH Plus, only at higher concentrations and in the HepG2 cell line. Concerning the two tested bioceramic sealers, BioRoot RCS showed higher tail intensity values compared to MTA Fillapex (p < 0.05). In contrast to the results of the comet assay, BioRoot RCS significantly reduced the number of nuclear buds and nucleoplasmic bridges in the HepG2 cell line compared to MTA Fillapex, whereas reduction in the V79 cell line was only observed for nuclear buds (p < 0.05). Both materials increased the number of apoptotic cells compared to the negative control (p < 0.05). In comparison to AH Plus, BioRoot RCS and MTA Fillapex significantly reduced the number of cells with micronuclei and increased the number of cells with undamaged chromatin (p < 0.05). Conclusions: The findings suggest that MTA Fillapex and BioRoot RCS exhibit superior biocompatibility over AH Plus, as evidenced by their lower cytotoxic and genotoxic effects in vitro. These results support the use of calcium silicate-based sealers in clinical practice, highlighting the need for further studies to evaluate their performance in vivo and their implications for patient safety. Full article

(This article belongs to the Section Dental Biomaterials)

► Show Figures

Figure 1

27 pages, 5228 KiB

Open AccessReview

Analysis of Biomechanical Characteristics of Bone Tissues Using a Bayesian Neural Network: A Narrative Review

by Nail Beisekenov, Marzhan Sadenova, Bagdat Azamatov and Boris Syrnev

J. Funct. Biomater. 2025, 16(5), 168; https://doi.org/10.3390/jfb16050168 - 8 May 2025

Abstract

Background: Bone elasticity is one of the most important biomechanical parameters of the skeleton. It varies markedly with age, anatomical zone, bone type (cortical or trabecular) and bone marrow status. Methods: This review presents the result of a systematic review and analysis of [...] Read more.

Background: Bone elasticity is one of the most important biomechanical parameters of the skeleton. It varies markedly with age, anatomical zone, bone type (cortical or trabecular) and bone marrow status. Methods: This review presents the result of a systematic review and analysis of 495 experimental and analytical papers on the elastic properties of bone tissue. The bone characteristics of hip, shoulder, skull, vertebrae as a function of the factors of age (young and old), sex (male and female), presence/absence of bone marrow and different test methods are examined. The Bayesian neural network (BNN) was used to estimate the uncertainty in some skeletal parameters (age, sex, and body mass index) in predicting bone elastic modulus. Results: It was found that the modulus of elasticity of cortical bone in young people is in the range of 10–30 GPa (depending on the type of bone), and with increasing age, this slightly decreases to 10–25 GPa, while trabecular tissue varies from 0.2 to 5 GPa and reacts more acutely to osteoporosis. Bone marrow, according to several studies, is able to partially increase stiffness under impact loading, but its contribution is minimal under slow deformations. Conclusions: BNN confirmed high variability, supplementing the predictions with confidence intervals and allowed the formation of equations for the calculation of bone tissue elastic modulus for the subsequent selection of the recommended elastic modulus of the finished implant, taking into account the biomechanical characteristics of bone tissue depending on age (young and old), sex (men and women) and anatomical zones of the human skeleton. Full article

(This article belongs to the Special Issue Biomaterials in Bone Reconstruction)

► Show Figures

Figure 1

15 pages, 3256 KiB

Open AccessArticle

Effect of Hyaluronan in Collagen Biomaterials on Human Macrophages and Fibroblasts In Vitro

by Nancy Avila-Martinez, Maren Pfirrmann, Madalena L. N. P. Gomes, Roman Krymchenko, Elly M. M. Versteeg, Marcel Vlig, Martijn Verdoes, Toin H. van Kuppevelt, Bouke K. H. L. Boekema and Willeke F. Daamen

J. Funct. Biomater. 2025, 16(5), 167; https://doi.org/10.3390/jfb16050167 - 8 May 2025

Abstract

In adults, scars are formed after deep skin wound injuries like burns. However, the fetal microenvironment allows for scarless skin regeneration. One component that is abundantly present in the fetal extracellular matrix is hyaluronan (HA). To study whether biomaterials with HA improve wound [...] Read more.

In adults, scars are formed after deep skin wound injuries like burns. However, the fetal microenvironment allows for scarless skin regeneration. One component that is abundantly present in the fetal extracellular matrix is hyaluronan (HA). To study whether biomaterials with HA improve wound healing, type I collagen scaffolds with and without HA were prepared and characterized. Their immune effect was tested using macrophages and their phenotypes were analyzed through cell surface markers and cytokine expression after 48 h. Since fibroblasts are the main cellular component in the dermis, adult, fetal and eschar-derived cells were cultured on scaffolds for 14 days and evaluated using histology, gene and protein expression analyses. Biochemical assays demonstrated that HA was successfully incorporated and evenly distributed throughout the scaffolds. Macrophages (M0) cultured on Col I+HA scaffolds exhibited a profile resembling the M2c-like phenotype (CD206^high, CD163^high and IL10^high). HA did not significantly affect gene expression in adult and fetal fibroblasts, but significantly reduced scarring-related genes, such as transforming growth factor beta 1 (TGFB1) and type X collagen alpha 1 chain (COL10A1), in myofibroblast-like eschar cells. These findings highlight the potential of incorporating HA into collagen-based skin substitutes to improve the wound healing response. Full article

(This article belongs to the Collection Feature Papers in Biomaterials for Tissue Engineering and Regenerative Medicine)

► Show Figures

Graphical abstract

33 pages, 10568 KiB

Open AccessReview

Emerging Trends in Microfluidic Biomaterials: From Functional Design to Applications

by Jiaqi Lin, Lijuan Cui, Xiaokun Shi and Shuping Wu

J. Funct. Biomater. 2025, 16(5), 166; https://doi.org/10.3390/jfb16050166 - 8 May 2025

Abstract

The rapid development of microfluidics has driven innovations in material engineering, particularly through its ability to precisely manipulate fluids and cells at microscopic scales. Microfluidic biomaterials, a cutting-edge interdisciplinary field integrating microfluidic technology with biomaterials science, are revolutionizing biomedical research. This review focuses [...] Read more.

The rapid development of microfluidics has driven innovations in material engineering, particularly through its ability to precisely manipulate fluids and cells at microscopic scales. Microfluidic biomaterials, a cutting-edge interdisciplinary field integrating microfluidic technology with biomaterials science, are revolutionizing biomedical research. This review focuses on the functional design and fabrication of organ-on-a-chip (OoAC) platforms via 3D bioprinting, explores the applications of biomaterials in drug delivery, cell culture, and tissue engineering, and evaluates the potential of microfluidic systems in advancing personalized healthcare. We systematically analyze the evolution of microfluidic materials—from silicon and glass to polymers and paper—and highlight the advantages of 3D bioprinting over traditional fabrication methods. Currently, despite significant advances in microfluidics in medicine, challenges in scalability, stability, and clinical translation remain. The future of microfluidic biomaterials will depend on combining 3D bioprinting with dynamic functional design, developing hybrid strategies that combine traditional molds with bio-printed structures, and using artificial intelligence to monitor drug delivery or tissue response in real time. We believe that interdisciplinary collaborations between materials science, micromachining, and clinical medicine will accelerate the translation of organ-on-a-chip platforms into personalized therapies and high-throughput drug screening tools. Full article

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

► Show Figures

Graphical abstract

19 pages, 6997 KiB

Open AccessArticle

Engineering Stepped Structures on Hydroxyapatite Surfaces: A Potential Strategy to Modulate Bone Marrow Mesenchymal Stem Adhesion, Spreading, and Proliferation

by Yongmei Wang, Fang Wang, Min Gong, Lidan Chen, Yun Wang, Pu Xu, Zhu Zeng, Zuquan Hu and Jin Chen

J. Funct. Biomater. 2025, 16(5), 165; https://doi.org/10.3390/jfb16050165 - 8 May 2025

Abstract

Constructing the surface structures of hydroxyapatite (HA) materials is a promising strategy for orchestrating the cell behaviors of bone marrow mesenchymal stem cells (BMSCs), beneficial for advancing BMSC-based tissue repair and regenerative therapies. The majority of previous strategies have focused on fabricating artificial [...] Read more.

Constructing the surface structures of hydroxyapatite (HA) materials is a promising strategy for orchestrating the cell behaviors of bone marrow mesenchymal stem cells (BMSCs), beneficial for advancing BMSC-based tissue repair and regenerative therapies. The majority of previous strategies have focused on fabricating artificial micro-/nano-scale geometric topographies or patterns on HA surfaces. Yet, constructing surface crystal defects has received insufficient attention and application, despite their importance as highlighted by theoretical calculations. This is largely due to the instability of crystal defects, which tend to be eliminated during crystallization. Here, given the fact that stepped structures are rich in stable crystal defects along their edges and kinks, we crafted HA dishes featuring stepped surfaces and utilized them to establish cell culture models of BMSCs. The outcomes revealed that the stepped structures markedly altered the physicochemical properties of HA surfaces and affected the cytoskeleton structures, spreading area, cell morphology, and focal adhesions of BMSCs in the cell culture model, resulting in inhibited cell adhesion. Given that YAP is a key mechanical sensitive factor, and its nuclear translocation is closely tied to cytoskeletal reorganization, the nuclear translocation efficiency of YAP has been investigated. The results showed that a changed cell adhesion could affect the nuclear translocation efficiency of YAP, which would be an important reason for the change in proliferation and differentiation ability of BMSCs. This work not only enhances the understanding of the responses of BMSCs to HA surface structures but also facilitates the design and optimization of HA materials. Moreover, our manufacturing method is facile and efficient, positioning it to potentially integrate with other processing techniques for the more effective and precise regulation of BMSCs. Full article

(This article belongs to the Section Bone Biomaterials)

► Show Figures

Figure 1

20 pages, 13885 KiB

Open AccessArticle

Biodegradable Double-Layer Hydrogels with Sequential Drug Release for Multi-Phase Collaborative Regulation in Scar-Free Wound Healing

by Xinyu Zhang, Qianhe Zu, Chunlin Deng, Xin Gao, Hongxu Liu, Yi Jin, Xinjian Yang and Enjun Wang

J. Funct. Biomater. 2025, 16(5), 164; https://doi.org/10.3390/jfb16050164 - 7 May 2025

Abstract

Scarring is a prevalent and often undesirable outcome of the wound healing process, impacting millions worldwide. The complex and dynamic nature of wound healing, including hemostasis, inflammation, proliferation, and remodeling, necessitates precise, making it hard for stage-specific interventions to prevent pathological scarring. This [...] Read more.

Scarring is a prevalent and often undesirable outcome of the wound healing process, impacting millions worldwide. The complex and dynamic nature of wound healing, including hemostasis, inflammation, proliferation, and remodeling, necessitates precise, making it hard for stage-specific interventions to prevent pathological scarring. This study introduces a double-layer hydrogel system designed for sequential drug release, aligning with the stage-specific need for wound healing. The lower layer, containing curcumin-loaded chitosan nanoparticles, shows early anti-inflammatory and antioxidant effects, while the upper layer, with pirfenidone-encapsulated gelatin microspheres, presents late-stage anti-fibrotic activity. The hydrogel’s unique design, with varying degradation rates and mechanical properties in each layer, facilitates cascade drug release in synchrony with wound healing stages. Rapid release of curcumin from the lower layer promotes proliferation by mitigating inflammation and oxidative stress, while the sustained release of pirfenidone from the upper layer inhibits excessive fibrillation during late proliferation and remodeling. In a rat model of full-thickness skin defect, treatment with a double-layer hydrogel drug delivery system accelerated the wound closure, improved scar quality, and promoted the formation of hair follicles. Therefore, this innovative approach lays a promising foundation for future clinical applications in anti-scar therapies, offering a significant advancement in wound care and regenerative medicine. Full article

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

► Show Figures

Figure 1

45 pages, 18946 KiB

Open AccessReview

Advancements in Musculoskeletal Tissue Engineering: The Role of Melt Electrowriting in 3D-Printed Scaffold Fabrication

by Kunal Ranat, Hong Phan, Suhaib Ellythy, Mitchell Kenter and Adil Akkouch

J. Funct. Biomater. 2025, 16(5), 163; https://doi.org/10.3390/jfb16050163 - 7 May 2025

Abstract

Musculoskeletal tissue injuries of the bone, cartilage, ligaments, tendons, and skeletal muscles are among the most common injuries experienced in medicine and become increasingly problematic in cases of significant tissue damage, such as nonunion bone defects and volumetric muscle loss. Current gold standard [...] Read more.

Musculoskeletal tissue injuries of the bone, cartilage, ligaments, tendons, and skeletal muscles are among the most common injuries experienced in medicine and become increasingly problematic in cases of significant tissue damage, such as nonunion bone defects and volumetric muscle loss. Current gold standard treatment options for musculoskeletal injuries, although effective, have limited capability to fully restore native tissue structure and function. To overcome this challenge, three-dimensional (3D) printing techniques have emerged as promising therapeutic options for tissue regeneration. Melt electrowriting (MEW), a recently developed advanced 3D printing technique, has gained significant traction in the field of tissue regeneration because of its ability to fabricate complex customizable scaffolds via high-precision microfiber deposition. The tailorability at microscale levels offered by MEW allows for enhanced recapitulation of the tissue microenvironment. Here, we survey the recent contributions of MEW in advancing musculoskeletal tissue engineering. More specifically, we briefly discuss the principles and technical aspects of MEW, provide an overview of current printers on the market, review in-depth the latest biomedical applications in musculoskeletal tissue regeneration, and, lastly, examine the limitations of MEW and offer future perspectives. Full article

(This article belongs to the Special Issue Recent Advances in 3D Printing of Biomaterials)

► Show Figures

Graphical abstract

18 pages, 7605 KiB

Open AccessArticle

Modulating Osteoclast Activity and Immune Responses with Ultra-Low-Dose Silver Nanoparticle-Loaded TiO₂ Nanotubes for Osteoporotic Bone Regeneration

by Zhen Wang, Penghui Xiang, Zhe Xu, Meiqi Gu, Rui Zhang, Yifei Li, Fei Xin and Chengla Yi

J. Funct. Biomater. 2025, 16(5), 162; https://doi.org/10.3390/jfb16050162 - 4 May 2025

Abstract

Introduction: Osteoporosis results from the dysregulation of osteoclast activation mechanisms. The subsequent inflammation in osteoporotic environments further hampers bone healing and impedes osseointegration. Therefore, developing treatments that can modulate osteoclast activity and regulate immune responses is essential for effectively treating osteoporotic bone defects. [...] Read more.

Introduction: Osteoporosis results from the dysregulation of osteoclast activation mechanisms. The subsequent inflammation in osteoporotic environments further hampers bone healing and impedes osseointegration. Therefore, developing treatments that can modulate osteoclast activity and regulate immune responses is essential for effectively treating osteoporotic bone defects. Methods: In this study, silver nanoparticle-decorated TiO₂ nanotubes (Ag@TiO₂-NTs) were synthesized through an electrochemical anodization technique for surface modification. The morphology and elemental composition of the Ag@TiO₂-NTs structures were characterized using scanning electron microscopy (SEM) and related methods. Subsequently, a series of in vitro and in vivo experiments were conducted to investigate the regenerative potential of Ag@TiO₂-NTs in osteoporotic bone defects. In vitro assays focused on evaluating cell viability and osteoclast function, while in vivo assessments employed osteoporotic rat models to monitor bone healing via histological examination and micro-computed tomography (micro-CT) imaging. Results: Our results demonstrated that Ag@TiO₂, through the controlled release of trace amounts of silver ions, significantly suppressed osteoclast activity and consequently alleviated bone resorption under osteoporotic conditions. In addition, Ag@TiO₂-NTs facilitated the polarization of macrophages toward the M2 phenotype. These biological effects were associated with the stimulation of autophagy, a fundamental mechanism involved in cellular repair. Moreover, the activation of autophagy contributed to the suppression of RANKL-induced NF-κB signaling, a pathway essential for the regulation of bone metabolism Conclusion: These results suggest that this surface modification strategy has the potential to be an ideal implant biomaterial for treating osteoporotic bone defects and a promising strategy for future implant surgeries. Full article

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

► Show Figures

Figure 1

39 pages, 8870 KiB

Open AccessReview

Bioglasses Versus Bioactive Calcium Phosphate Derivatives as Advanced Ceramics in Tissue Engineering: Comparative and Comprehensive Study, Current Trends, and Innovative Solutions

by Monika Furko

J. Funct. Biomater. 2025, 16(5), 161; https://doi.org/10.3390/jfb16050161 - 3 May 2025

Abstract

Tissue engineering represents a revolutionary approach to regenerating damaged bones and tissues. The most promising materials for this purpose are calcium phosphate-based bioactive ceramics (CaPs) and bioglasses, due to their excellent biocompatibility, osteoconductivity, and bioactivity. This review aims to provide a comprehensive and [...] Read more.

Tissue engineering represents a revolutionary approach to regenerating damaged bones and tissues. The most promising materials for this purpose are calcium phosphate-based bioactive ceramics (CaPs) and bioglasses, due to their excellent biocompatibility, osteoconductivity, and bioactivity. This review aims to provide a comprehensive and comparative analysis of different bioactive calcium phosphate derivatives and bioglasses, highlighting their roles and potential in both bone and soft tissue engineering as well as in drug delivery systems. We explore their applications as composites with natural and synthetic biopolymers, which can enhance their mechanical and bioactive properties. This review critically examines the advantages and limitations of each material, their preparation methods, biological efficacy, biodegradability, and practical applications. By summarizing recent research from scientific literature, this paper offers a detailed analysis of the current state of the art. The novelty of this work lies in its systematic comparison of bioactive ceramics and bioglasses, providing insights into their suitability for specific tissue engineering applications. The expected primary outcomes include a deeper understanding of how each material interacts with biological systems, their suitability for specific applications, and the implications for future research directions. Full article

(This article belongs to the Special Issue Advanced Bioglasses, Bioceramics and Their Composites: State-of-the-Art and Applications)

► Show Figures

Figure 1

15 pages, 3084 KiB

Open AccessArticle

Tumor-Treating Fields Alter Nanomechanical Properties of Pancreatic Ductal Adenocarcinoma Cells Co-Cultured with Extracellular Matrix

by Tanmay Kulkarni, Sreya Banik, Debabrata Mukhopadhyay, Hani Babiker and Santanu Bhattacharya

J. Funct. Biomater. 2025, 16(5), 160; https://doi.org/10.3390/jfb16050160 - 3 May 2025

Abstract

Tumor-Treating Fields (TTFields), a novel therapeutic avenue, is approved for therapy in Glioblastoma multiforme, malignant pleural mesothelioma, and metastatic non-small cell lung cancer (NSCLC). In pancreatic ductal adenocarcinoma (PDAC), several clinical trials are underway to improve outcomes, yet a significant knowledge gap prevails [...] Read more.

Tumor-Treating Fields (TTFields), a novel therapeutic avenue, is approved for therapy in Glioblastoma multiforme, malignant pleural mesothelioma, and metastatic non-small cell lung cancer (NSCLC). In pancreatic ductal adenocarcinoma (PDAC), several clinical trials are underway to improve outcomes, yet a significant knowledge gap prevails involving the cell-extracellular matrix (ECM) crosstalk. Herein, we hypothesized that treatment with TTFields influence this crosstalk, which is reflected by the dynamic alteration in nanomechanical properties (NMPs) of cells and the ECM in a co-culture system. We employed an ECM gel comprising collagen, fibronectin, and laminin mixed in 100:1:1 stoichiometry to co-culture of Panc1 and AsPC1 individually. This ECM mixture mimics the in vivo tumor microenvironment closely when compared to the individual ECM components studied before. A comprehensive frequency-dependent study revealed the optimal TTFields frequency to be 150 kHz. We also observed that irrespective of the ECM’s presence, TTFields increase cell membrane stiffness and decrease deformation several-folds in both Panc1 and AsPC1 cells at both 48 h and 72 h. Although adhesion for AsPC1 decreased at 48 h, at 72 h it was observed to increase irrespective of ECM’s presence. Moreover, it significantly alters the NMPs of ECM gels when co-cultured with PDAC cell lines. However, AsPC1 cells were observed to be more detrimental to these changes. Lastly, we attribute the stiffness changes in Panc1 cells to the membrane F-actin reorganization in the presence of TTFields. This study paves a path to study complex PDAC TME as well as the effect of various chemotherapeutic agents on such TME with TTFields in the future. Full article

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

► Show Figures

Figure 1

16 pages, 4209 KiB

Open AccessArticle

Squid Skin Decellularised Dermal Matrix for Enhancing Repair of Acute Cranial Injuries in Rabbit Model

by Lixin Liu, Yida Pang, Haoze Yang, Qiyi Zhou, JinHua Hou, Wenhui Wu and Jeevithan Elango

J. Funct. Biomater. 2025, 16(5), 159; https://doi.org/10.3390/jfb16050159 - 30 Apr 2025

Abstract

Squid skin decellularized dermal matrix (SADM) is gaining attention in tissue engineering and regenerative medicine due to its mimicking of the extracellular matrix property. Hence, SADM was used to investigate mimicking the microenvironment of cellular growth, inducing cellular infiltration and angiogenesis, and facilitating [...] Read more.

Squid skin decellularized dermal matrix (SADM) is gaining attention in tissue engineering and regenerative medicine due to its mimicking of the extracellular matrix property. Hence, SADM was used to investigate mimicking the microenvironment of cellular growth, inducing cellular infiltration and angiogenesis, and facilitating the repair of acute craniofacial wounds. For this, tissue regeneration membranes from squid skin were prepared by decolorization, degreasing and decellularisation methods. The effect of SADM in guiding bone tissue regeneration was evaluated using the rabbit skull bone defect model. SEM images of SADM had a bilayer membrane architecture characterized by a reticulated porous structure on one side and a dense, non-porous surface on the opposite side. Notably, the water absorption capacity of SADM was approximately eight times higher than its weight, exhibiting a porosity of 58% and a peak average tensile stress of 10.43 MPa. Additionally, simulations of tissue fluid degradation indicated a degradation rate of 70.42% and 88.33% on days 8 and 12, respectively. Following 4 and 8 weeks of animal studies focused on repairing cranial bone defects in rabbits, the findings demonstrated that SADM served as an effective barrier against fibrous connective tissue, promoted the proliferation of osteoblasts, and supported bone regeneration. This was confirmed through micro-CT imaging, and sections were stained with senna solid green. In summary, SADM is capable of directing cell infiltration and bone tissue formation, modulating the expression and secretion of inflammatory and skin repair-related factors, thereby enhancing tissue healing. Full article

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

► Show Figures

Graphical abstract

22 pages, 4153 KiB

Open AccessReview

Bioinspired Soft Machines: Engineering Nature’s Grace into Future Innovations

by Ajay Vikram Singh, Mohammad Hasan Dad Ansari, Arindam K. Dey, Peter Laux, Shailesh Kumar Samal, Paolo Malgaretti, Soumya Ranjan Mohapatra, Madleen Busse, Mrutyunjay Suar, Veronica Tisato and Donato Gemmati

J. Funct. Biomater. 2025, 16(5), 158; https://doi.org/10.3390/jfb16050158 - 28 Apr 2025

Abstract

This article explores the transformative advances in soft machines, where biology, materials science, and engineering have converged. We discuss the remarkable adaptability and versatility of soft machines, whose designs draw inspiration from nature’s elegant solutions. From the intricate movements of octopus tentacles to [...] Read more.

This article explores the transformative advances in soft machines, where biology, materials science, and engineering have converged. We discuss the remarkable adaptability and versatility of soft machines, whose designs draw inspiration from nature’s elegant solutions. From the intricate movements of octopus tentacles to the resilience of an elephant’s trunk, nature provides a wealth of inspiration for designing robots capable of navigating complex environments with grace and efficiency. Central to this advancement is the ongoing research into bioinspired materials, which serve as the building blocks for creating soft machines with lifelike behaviors and adaptive capabilities. By fostering collaboration and innovation, we can unlock new possibilities in soft machines, shaping a future where robots seamlessly integrate into and interact with the natural world, offering solutions to humanity’s most pressing challenges. Full article

(This article belongs to the Special Issue 15th Anniversary of JFB—Bioinspired Materials for Medical Applications)

► Show Figures

Figure 1

24 pages, 17467 KiB

Open AccessArticle

Combined Effects of Dual-Scale Modified Surface with Micro- and Nanostructures on the Cellular Biocompatibility, Osteoinduction, and Antibacterial Properties of Titanium Implants

by Shaheer Maher, Nenad L. Ignjatović, Miloš Lazarević, Sanja Petrović, Andrijana Žekić and Dusan Losic

J. Funct. Biomater. 2025, 16(5), 157; https://doi.org/10.3390/jfb16050157 - 28 Apr 2025

Abstract

Titanium implants are widely used in biomedical applications due to their excellent mechanical properties and biocompatibility. However, implant-associated bacterial infections and suboptimal osseointegration remain significant challenges. Recent studies have demonstrated that the interplay between micro- and nanostructures can enhance both biocompatibility and antibacterial [...] Read more.

Titanium implants are widely used in biomedical applications due to their excellent mechanical properties and biocompatibility. However, implant-associated bacterial infections and suboptimal osseointegration remain significant challenges. Recent studies have demonstrated that the interplay between micro- and nanostructures can enhance both biocompatibility and antibacterial properties. This study explores the synergistic effects of hierarchical and dual surface topography on Ti surfaces with micro- and nanostructures to demonstrate their ability to promote cellular biocompatibility and osteoinduction while simultaneously inhibiting bacterial colonization. The combination of selective laser melting (SLM) to create micro-structured surfaces and hydrothermal processes is used to generate distinctive nanopillar structures. By integrating nanoscale features that mimic the extracellular matrix with microscale topographies that influence cellular responses, we achieve a balance between enhanced osseointegration and antimicrobial performance. The physicochemical properties of these dual-scale topographies are characterized through cellular assays using dental pulp stem cells (DPSCs), demonstrating sustained support for long-term cell viability (above 78% in MTT and NR assays (p < 0.05), low levels of LDH release, and high levels of cellular migration) and osteoinduction (statistically significant (p < 0.0001) ALP activity increase and higher levels of calcified matrix deposition, upregulation of ALP and OCN genes compared with smooth surface topographies). Their antibacterial properties against S. aureus and E. coli showed a significant reduction (p < 0.05) in bacterial attachment and biofilm formation. Our findings highlight the potential of multi-scale surface modifications as a promising strategy for next-generation titanium implants, paving the way for improved clinical outcomes in orthopedic and dental applications. Full article

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

► Show Figures

Figure 1

18 pages, 7250 KiB

Open AccessArticle

The Influence of Thermocycling and Ultraviolet Aging on Surface Characteristics and the Repair Bond Strength of CAD/CAM Resin Nanoceramics

by Beyza Unalan Degirmenci, Alperen Degirmenci and Zelal Seyfioglu Polat

J. Funct. Biomater. 2025, 16(5), 156; https://doi.org/10.3390/jfb16050156 - 28 Apr 2025

Abstract

Background: The durability of computer-aided design/computer-aided manufacturing (CAD/CAM) resin nanoceramics in the oral environment is influenced by aging factors such as thermocycling and ultraviolet (UV) exposure. This study investigates the impact of these aging processes on surface characteristics and repair bond strength. Methods: [...] Read more.

Background: The durability of computer-aided design/computer-aided manufacturing (CAD/CAM) resin nanoceramics in the oral environment is influenced by aging factors such as thermocycling and ultraviolet (UV) exposure. This study investigates the impact of these aging processes on surface characteristics and repair bond strength. Methods: CAD/CAM resin nanoceramic samples were divided into the following five groups: control (non-aged), 1-year and 5-year thermocycling, and 1-year and 5-year UV aging (n = 12). For the thermocycling procedure, the parameters employed were a temperature range of 5–55 °C with dwell times of 20 s per bath and 10,000 and 50,000 cycles; for the ultraviolet aging process, the parameters were established at a wavelength of 340 nm, an intensity of 0.55 W/m², and durations of 300 h and 1500 h. Surface roughness, microhardness, and repair bond strength were analyzed through profilometry, Vickers microhardness testing, and shear bond strength assessment, respectively. SEM, AFM, and XRD analyses were performed for structural evaluation. Results: Both thermocycling and UV aging significantly increased surface roughness (p < 0.001) while reducing microhardness and repair bond strength (p < 0.001). UV aging had a more pronounced effect, particularly after five years, leading to the highest surface roughness (Ra: 61.77 μm; Rz: 271.57 μm) and lowest microhardness properties (63.13). EDAX analysis indicated matrix degradation and an increase in inorganic filler exposure. Conclusions: Aging significantly affects the surface characteristics of CAD/CAM resin nanoceramics, with UV aging exhibiting the most detrimental impact. These findings highlight the necessity of considering long-term material stability in dentistry. Full article

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

► Show Figures

Figure 1

12 pages, 2965 KiB

Open AccessArticle

Correlation Between Polymerization Shrinkage and Filler Content for Universal Shade Flowable Resin-Based Composites

by Nagisa Matsui, Mayumi Maesako, Ahmad Alkhazaleh, Masao Irie and Akimasa Tsujimoto

J. Funct. Biomater. 2025, 16(5), 155; https://doi.org/10.3390/jfb16050155 - 28 Apr 2025

Abstract

The purpose of this study was to measure the filler content by weight and volume of universal shade flowable resin-based composites and analyze the correlation between polymerization shrinkage and filler content. The filler content by weight of six universal shade flowalble resin-based composites [...] Read more.

The purpose of this study was to measure the filler content by weight and volume of universal shade flowable resin-based composites and analyze the correlation between polymerization shrinkage and filler content. The filler content by weight of six universal shade flowalble resin-based composites (Bulk Base Hard II Medium Flow, A-Uno Flow Basic, Clearfil Majesty ES Flow Low, Gracefill Low Flow, Omnichroma Flow, Omnichroma Flow Bulk) was measured in accordance with ISO 17304. The filler content by volume of each flowable resin-based composite was determined by measuring the density of the filler using a dry density meter, and the filler content by volume of the composite was calculated from the densities obtained. The correlations between filler content by weight or volume, polymerization shrinkage and filler content by weight ratio, and polymerization shrinkage and filler content by volume were analyzed. The filler content of the universal flowable resin-based composites ranged from 59.40 to 69.81% (by weight) and from 40.61 to 54.84% (by volume), and the correlations between the values for filler content of the composites by weight and volume were weakly negative and not statistically significant. The correlations between polymerization shrinkage (3.15–4.48%) and filler content by weight or volume were also not statistically significant. Full article

(This article belongs to the Special Issue Ceramic, Zirconia, and Resin-Based Composite for Restorative Dentistry)

► Show Figures

Figure 1

5 pages, 190 KiB

Open AccessEditorial

Functional Biomaterials: Scaffolds for Innovative Treatments

by Cristian Scheau, Andreea Cristiana Didilescu and Constantin Caruntu

J. Funct. Biomater. 2025, 16(5), 154; https://doi.org/10.3390/jfb16050154 - 27 Apr 2025

Abstract

Numerous therapies for a multitude of pathologies have reached their limits [...] Full article

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

Journal Description

Journal of Functional Biomaterials

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI