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Comparative Analysis of Matrigel and Tunable Collagen-Fibrin Blends for in Vitro Skeletal Muscle Models. 基质型和可调型胶原-纤维蛋白混合物用于体外骨骼肌模型的比较分析。
IF 3.9 Pub Date : 2026-02-01 DOI: 10.1002/jbma.70039
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.

在这项研究中,我们描述了胶原蛋白(COL)、纤维蛋白(FIB)、透明质酸(HA)和层粘连蛋白(LAM)互穿网络的凝胶动力学、细胞相容性和力学特性,以评估它们产生成熟骨骼肌组织的潜力。骨骼肌是一种动态组织,依靠成肌细胞融合成多核肌纤维来维持体内平衡。在进行性退行性疾病中,成肌细胞融合受损导致骨骼肌萎缩和显著的质量损失。为了更好地了解疾病机制和促进药物筛选,骨骼肌疾病的三维(3D)体外模型已经开发出来。然而,大多数依赖于Matrigel,一种肿瘤来源的基质,支持强劲的细胞生长,但临床相关性有限。为了解决这一限制,我们专注于创造天然的、多组分的支架,专门为临床相关药物测试的肌肉应用量身定制。利用分光光度法和流变学,我们表征了不同质量比的COL和FIB,以及固定比例的HA和LAM的互穿网络的凝胶动力学和粘弹性。可调凝胶在10至16分钟的范围内实现。与C2C12小鼠成肌细胞的细胞相容性研究表明,在含有HA和LAM的1:1和1:2 (w/w) COL:FIB混合物中,细胞活力良好。当将分化的C2C12细胞植入聚二甲基硅氧烷(PDMS)锚定束时,免疫染色证实了这些混合物中Myosin 4单克隆抗体(MF-20)的表达。值得注意的是,在种子密度为10 × 106细胞/mL的1:1 COL:FIB凝胶中,压缩模量在分化的第4天至第7天增加了3倍。这些发现突出了COL:FIB互穿网络的潜力,通过HA和LAM增强,作为开发临床相关骨骼肌组织模型的有希望的支架。
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引用次数: 0
Bioactive ZnO Decorated PVDF-Based Piezoelectric, Osteoconductive Nanofibrous Coatings for Orthopedic Implants. 生物活性ZnO修饰pvdf基压电、骨导电性纳米纤维涂层用于骨科植入物。
IF 3.9 Pub Date : 2025-08-01 DOI: 10.1002/jbm.a.37971
Sumedh Vaidya, Mansi Joshi, Sumanta Ghosh, Namdev More, Ravichandiran Velyutham, Srivalliputtur Sarath Babu, Govinda Kapusetti

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.

在过去的几十年里,人们一直在研究钛基骨科植入物的表面改性,以促进更好的骨与植入物的结合、骨整合和骨折愈合。然而,由于包被材料黏附强度差、疲劳失效、磨损率高、生物相容性低、骨整合受限、应力屏蔽作用等原因,导致包被骨科种植体术后失效。因此,开发一种智能涂层策略是尚未满足的临床需求。在此,我们利用压电聚偏氟乙烯(PVDF)聚合物和骨导电性纳米填料氧化锌(ZnO)增强,创造了一种用于钛植入物的电纺纳米纤维涂层。我们发现,通过改变ZnO含量从0.5到2.0 wt。在PVDF基体中,我们可以调节静电纺涂层的机械、热、物理化学稳定性和压电特性。我们的研究结果证明,与纯PVDF相比,PVDF- zno纳米纤维涂层的压电d33系数和输出电压几乎增加了~3-4倍。此外,与未极化纳米纤维相比,电极化压电PVDF-ZnO纳米纤维在胶原沉积、羟基磷灰石形成以及生物和血液相容性方面也有显著增加(约5倍)。此外,通过体外实验,我们证实压电型PVDF-ZnO纳米纤维激活钙-钙调素介导的细胞通路,诱导成骨细胞的细胞粘附、增殖和细胞扩散。尽管如此,使用仿生机械生物反应器,我们研究了骨细胞在生理相关(即1%)机械应变下,压电介导的局灶粘连增加和f -肌动蛋白生成增强。此外,目前的研究阐明了基于压电的智能多功能涂层策略,用于开发骨传导植入物。
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引用次数: 0
Correction to "Photocrosslinkable and elastomeric hydrogels for bone regeneration". 更正“用于骨再生的光交联和弹性水凝胶”。
IF 3.9 Pub Date : 2025-08-01 DOI: 10.1002/jbm.a.37974
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引用次数: 0
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