Journal of Functional Biomaterials最新文献

{"title":"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.","authors":"Antonija Tadin, Marija Badrov, Danijela Juric Kacunic, Nada Galic, Matea Macan, Ivan Kovacic, Davor Zeljezic","doi":"10.3390/jfb16050169","DOIUrl":"10.3390/jfb16050169","url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Materials and methods: </strong>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 (<i>p</i> < 0.05).</p><p><strong>Results: </strong>At lower concentrations in both cell lines, MTA Fillapex showed no significant difference in the measured comet assay parameters compared to the negative control (<i>p</i> > 0.05). In addition, it showed significantly lower genotoxic effects compared to AH Plus for all comet assay parameters, concentrations, and cell lines (<i>p</i> ≤ 0.001). BioRoot RCS showed lower primary DNA damage (<i>p</i> ≤ 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 (<i>p</i> < 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 (<i>p</i> < 0.05). Both materials increased the number of apoptotic cells compared to the negative control (<i>p</i> < 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 (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Six-Year Implants Follow-Up After Guided Bone Regeneration Using Autologous Tooth Graft: Innovative Biomaterial for Bone Regeneration Tooth Transformer^®.","authors":"Elio Minetti, Angelo Michele Inchingolo, Laura Ferrante, Grazia Marinelli, Francesco Inchingolo, Alessio Danilo Inchingolo, Andrea Palermo, Gianna Dipalma","doi":"10.3390/jfb16050172","DOIUrl":"10.3390/jfb16050172","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12111868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Stepped Structures on Hydroxyapatite Surfaces: A Potential Strategy to Modulate Bone Marrow Mesenchymal Stem Adhesion, Spreading, and Proliferation.","authors":"Yongmei Wang, Fang Wang, Min Gong, Lidan Chen, Yun Wang, Pu Xu, Zhu Zeng, Zuquan Hu, Jin Chen","doi":"10.3390/jfb16050165","DOIUrl":"10.3390/jfb16050165","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Hyaluronan in Collagen Biomaterials on Human Macrophages and Fibroblasts <i>In Vitro</i>.","authors":"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, Willeke F Daamen","doi":"10.3390/jfb16050167","DOIUrl":"10.3390/jfb16050167","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Trends in Microfluidic Biomaterials: From Functional Design to Applications.","authors":"Jiaqi Lin, Lijuan Cui, Xiaokun Shi, Shuping Wu","doi":"10.3390/jfb16050166","DOIUrl":"10.3390/jfb16050166","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Biomechanical Characteristics of Bone Tissues Using a Bayesian Neural Network: A Narrative Review.","authors":"Nail Beisekenov, Marzhan Sadenova, Bagdat Azamatov, Boris Syrnev","doi":"10.3390/jfb16050168","DOIUrl":"10.3390/jfb16050168","url":null,"abstract":"<p><p><i>Background:</i> 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. <i>Methods:</i> 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. <i>Results:</i> 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. <i>Conclusions:</i> 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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Musculoskeletal Tissue Engineering: The Role of Melt Electrowriting in 3D-Printed Scaffold Fabrication.","authors":"Kunal Ranat, Hong Phan, Suhaib Ellythy, Mitchell Kenter, Adil Akkouch","doi":"10.3390/jfb16050163","DOIUrl":"10.3390/jfb16050163","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodegradable Double-Layer Hydrogels with Sequential Drug Release for Multi-Phase Collaborative Regulation in Scar-Free Wound Healing.","authors":"Xinyu Zhang, Qianhe Zu, Chunlin Deng, Xin Gao, Hongxu Liu, Yi Jin, Xinjian Yang, Enjun Wang","doi":"10.3390/jfb16050164","DOIUrl":"10.3390/jfb16050164","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12111865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating Osteoclast Activity and Immune Responses with Ultra-Low-Dose Silver Nanoparticle-Loaded TiO₂ Nanotubes for Osteoporotic Bone Regeneration.","authors":"Zhen Wang, Penghui Xiang, Zhe Xu, Meiqi Gu, Rui Zhang, Yifei Li, Fei Xin, Chengla Yi","doi":"10.3390/jfb16050162","DOIUrl":"10.3390/jfb16050162","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-Treating Fields Alter Nanomechanical Properties of Pancreatic Ductal Adenocarcinoma Cells Co-Cultured with Extracellular Matrix.","authors":"Tanmay Kulkarni, Sreya Banik, Debabrata Mukhopadhyay, Hani Babiker, Santanu Bhattacharya","doi":"10.3390/jfb16050160","DOIUrl":"10.3390/jfb16050160","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"16 5","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}