Jorge A Mojica-Santiago, Gopal Agarwal, Steven Robles-Blasini, Isabella C Young, Victor A Lopez, Shelby Giza, Aaron Choi, Siobhan Malany, Christine E Schmidt
In this study, we describe the gelation kinetics, cytocompatibility, and mechanical properties of interpenetrating networks of collagen (COL), fibrin (FIB), hyaluronan (HA), and laminin (LAM) to evaluate their potential to produce mature skeletal muscle tissue. Skeletal muscle is a dynamic tissue that relies on the fusion of myoblasts into multinucleated myofibers to maintain homeostasis. In progressively degenerative conditions, impaired myoblast fusion leads to skeletal muscle atrophy and significant mass loss. Three-dimensional (3D) in vitro models for skeletal muscle disease have been developed to better understand disease mechanisms and facilitate drug screening. However, most rely on Matrigel, a tumor-derived matrix that supports robust cell growth but has limited clinical relevance. To address this limitation, we focused on creating natural, multi-component scaffolds specifically tailored for muscle applications with clinically relevant drug testing use. Using spectrophotometry and rheology, we characterized the gelation kinetics and viscoelastic properties of interpenetrating networks with varying mass ratios of COL to FIB, supplemented with fixed proportions of HA and LAM. Tunable gelation was achieved within a range of 10 to 16 min. Cytocompatibility studies with C2C12 murine myoblasts demonstrated favorable cell viability in 1:1 and 1:2 (w/w) COL:FIB blends incorporating HA and LAM. Immunostaining of differentiated C2C12 cells confirmed Myosin 4 Monoclonal Antibody (MF-20) expression in these blends when seeded into polydimethylsiloxane (PDMS)-anchored bundles. Notably, in cell-laden 1:1 COL:FIB gels with a seeding density of 10 × 106 cells/mL, the compressive modulus increased three-fold between days 4 and 7 of differentiation. These findings highlight the potential of COL:FIB interpenetrating networks, enhanced with HA and LAM, as promising scaffolds for developing clinically relevant models of skeletal muscle tissue.
{"title":"Comparative Analysis of Matrigel and Tunable Collagen-Fibrin Blends for in Vitro Skeletal Muscle Models.","authors":"Jorge A Mojica-Santiago, Gopal Agarwal, Steven Robles-Blasini, Isabella C Young, Victor A Lopez, Shelby Giza, Aaron Choi, Siobhan Malany, Christine E Schmidt","doi":"10.1002/jbma.70039","DOIUrl":"https://doi.org/10.1002/jbma.70039","url":null,"abstract":"<p><p>In this study, we describe the gelation kinetics, cytocompatibility, and mechanical properties of interpenetrating networks of collagen (COL), fibrin (FIB), hyaluronan (HA), and laminin (LAM) to evaluate their potential to produce mature skeletal muscle tissue. Skeletal muscle is a dynamic tissue that relies on the fusion of myoblasts into multinucleated myofibers to maintain homeostasis. In progressively degenerative conditions, impaired myoblast fusion leads to skeletal muscle atrophy and significant mass loss. Three-dimensional (3D) in vitro models for skeletal muscle disease have been developed to better understand disease mechanisms and facilitate drug screening. However, most rely on Matrigel, a tumor-derived matrix that supports robust cell growth but has limited clinical relevance. To address this limitation, we focused on creating natural, multi-component scaffolds specifically tailored for muscle applications with clinically relevant drug testing use. Using spectrophotometry and rheology, we characterized the gelation kinetics and viscoelastic properties of interpenetrating networks with varying mass ratios of COL to FIB, supplemented with fixed proportions of HA and LAM. Tunable gelation was achieved within a range of 10 to 16 min. Cytocompatibility studies with C2C12 murine myoblasts demonstrated favorable cell viability in 1:1 and 1:2 (w/w) COL:FIB blends incorporating HA and LAM. Immunostaining of differentiated C2C12 cells confirmed Myosin 4 Monoclonal Antibody (MF-20) expression in these blends when seeded into polydimethylsiloxane (PDMS)-anchored bundles. Notably, in cell-laden 1:1 COL:FIB gels with a seeding density of 10 × 10<sup>6</sup> cells/mL, the compressive modulus increased three-fold between days 4 and 7 of differentiation. These findings highlight the potential of COL:FIB interpenetrating networks, enhanced with HA and LAM, as promising scaffolds for developing clinically relevant models of skeletal muscle tissue.</p>","PeriodicalId":94066,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 2","pages":"e70039"},"PeriodicalIF":3.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Surface modification of titanium-based orthopedic implants has been investigated over the last decades to promote better bone-to-implant association, osseointegration, and fracture healing. Yet, post-surgical failure of coated orthopedic implants occurs due to poor adhesive strength, fatigue failure, high wear rate of coated materials, low biocompatibility, limited osseointegration, and stress-shielding effect. Therefore, there is an unmet clinical need to develop a smart coating strategy. Herein, we have created an electrospun nanofibrous coating for Ti-implants using piezoelectric Polyvinylidene fluoride (PVDF) polymer reinforced with osteoconductive nanofiller Zinc oxide (ZnO). We have found that by varying the ZnO content from 0.5 to 2.0 wt.% in the PVDF matrix, we can modulate the electrospun coating's mechanical, thermal, physicochemical stability, and piezoelectric characteristics. Our results proved that PVDF-ZnO nanofibrous coatings exhibit almost ~3-4 fold increase in the piezoelectric d33 coefficient as well as output voltage, compared to pure PVDF using Piezo-responsive Force Microscopy (PFM). Furthermore, electrically poled piezoelectric PVDF-ZnO nanofibers also demonstrated a significant increment (~5-fold) in collagen deposition, hydroxyapatite formation, and improved bio- and hemo-compatibility compared to unpoled nanofibers. Furthermore, through the in vitro experiments, we have confirmed that the piezoelectric PVDF-ZnO nanofibrous activates calcium-calmodulin mediated cellular pathway to induce cell adhesion, proliferation, and cell spreading in the osteoblast cells. Nonetheless, using the biomimetic mechanical bioreactor, we have investigated the piezoelectricity-mediated increased focal adhesion and enhanced F-actin production under the physiologically relevant (i.e., 1%) mechanical strain in bone cells. Moreover, the current study elucidates the piezoelectric-based smart, multifunctional coating strategies for developing an osteoconductive implant.
{"title":"Bioactive ZnO Decorated PVDF-Based Piezoelectric, Osteoconductive Nanofibrous Coatings for Orthopedic Implants.","authors":"Sumedh Vaidya, Mansi Joshi, Sumanta Ghosh, Namdev More, Ravichandiran Velyutham, Srivalliputtur Sarath Babu, Govinda Kapusetti","doi":"10.1002/jbm.a.37971","DOIUrl":"https://doi.org/10.1002/jbm.a.37971","url":null,"abstract":"<p><p>Surface modification of titanium-based orthopedic implants has been investigated over the last decades to promote better bone-to-implant association, osseointegration, and fracture healing. Yet, post-surgical failure of coated orthopedic implants occurs due to poor adhesive strength, fatigue failure, high wear rate of coated materials, low biocompatibility, limited osseointegration, and stress-shielding effect. Therefore, there is an unmet clinical need to develop a smart coating strategy. Herein, we have created an electrospun nanofibrous coating for Ti-implants using piezoelectric Polyvinylidene fluoride (PVDF) polymer reinforced with osteoconductive nanofiller Zinc oxide (ZnO). We have found that by varying the ZnO content from 0.5 to 2.0 wt.% in the PVDF matrix, we can modulate the electrospun coating's mechanical, thermal, physicochemical stability, and piezoelectric characteristics. Our results proved that PVDF-ZnO nanofibrous coatings exhibit almost ~3-4 fold increase in the piezoelectric d<sub>33</sub> coefficient as well as output voltage, compared to pure PVDF using Piezo-responsive Force Microscopy (PFM). Furthermore, electrically poled piezoelectric PVDF-ZnO nanofibers also demonstrated a significant increment (~5-fold) in collagen deposition, hydroxyapatite formation, and improved bio- and hemo-compatibility compared to unpoled nanofibers. Furthermore, through the in vitro experiments, we have confirmed that the piezoelectric PVDF-ZnO nanofibrous activates calcium-calmodulin mediated cellular pathway to induce cell adhesion, proliferation, and cell spreading in the osteoblast cells. Nonetheless, using the biomimetic mechanical bioreactor, we have investigated the piezoelectricity-mediated increased focal adhesion and enhanced F-actin production under the physiologically relevant (i.e., 1%) mechanical strain in bone cells. Moreover, the current study elucidates the piezoelectric-based smart, multifunctional coating strategies for developing an osteoconductive implant.</p>","PeriodicalId":94066,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 8","pages":"e37971"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Photocrosslinkable and elastomeric hydrogels for bone regeneration\".","authors":"","doi":"10.1002/jbm.a.37974","DOIUrl":"https://doi.org/10.1002/jbm.a.37974","url":null,"abstract":"","PeriodicalId":94066,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 8","pages":"e37974"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}