Department of Biomedical Engineering, University of Connecticut, Farmington, CT 06030, USA.
Department of Molecular, Cellular & Biomedical Sciences, The City College of New York, New York, NY, 10031, USA.
Nanoscale. 2022 Jan 20;14(3):797-814. doi: 10.1039/d1nr06143g.
Extreme loss of skeletal muscle overwhelms the natural regenerative capability of the body, results in permanent disability and substantial economic burden. Current surgical techniques result in poor healing, secondary injury to the autograft donor site, and incomplete recuperation of muscle function. Most current tissue engineering and regenerative strategies fail to create an adequate mechanical and biological environment that enables cell infiltration, proliferation, and myogenic differentiation. In this study, we present a nanoengineered skeletal muscle scaffold based on functionalized gelatin methacrylate (GelMA) hydrogel, optimized for muscle progenitors' proliferation and differentiation. The scaffold was capable of controlling the release of insulin-like growth factor 1 (IGF-1), an important myogenic growth factor, by utilizing the electrostatic interactions with LAPONITE nanoclays (NCs). Physiologically relevant levels of IGF-1 were maintained during a controlled release over two weeks. The NC was able to retain 50% of the released IGF-1 within the hydrogel niche, significantly improving cellular proliferation and differentiation compared to control hydrogels. IGF-1 supplemented medium controls required 44% more IGF-1 than the comparable NC hydrogel composites. The nanofunctionalized scaffold is a viable option for the treatment of extreme muscle injuries and offers scalable benefits for translational interventions and the growing field of clean meat production.
骨骼肌的极度丧失会超出身体的自然再生能力,导致永久性残疾和巨大的经济负担。目前的手术技术导致愈合不良、对供体部位的自体移植物的二次损伤,以及肌肉功能无法完全恢复。大多数当前的组织工程和再生策略无法创建一个足够的机械和生物环境,使细胞能够渗透、增殖和肌源性分化。在这项研究中,我们提出了一种基于功能化明胶甲基丙烯酰胺(GelMA)水凝胶的纳米工程化骨骼肌支架,该支架经过优化,可促进肌肉祖细胞的增殖和分化。该支架能够通过与 LAPONITE 纳米粘土(NC)的静电相互作用来控制胰岛素样生长因子 1(IGF-1)的释放,IGF-1 是一种重要的肌生成生长因子。在两周的控制释放过程中,能够维持生理相关水平的 IGF-1。NC 能够将释放的 IGF-1 的 50%保留在水凝胶龛内,与对照水凝胶相比,显著提高了细胞增殖和分化。与可比的 NC 水凝胶复合材料相比,添加 IGF-1 的培养基对照需要多 44%的 IGF-1。这种纳米功能化支架是治疗严重肌肉损伤的可行选择,并为转化干预和日益发展的清洁肉类生产领域提供了可扩展的益处。