Habing Krista M, Alcazar Cynthia A, Dobson Nathaniel, Tan Yong How, Huang Ngan F, Nakayama Karina H
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Bioengineering (Basel). 2024 Dec 14;11(12):1269. doi: 10.3390/bioengineering11121269.
A primary challenge following severe musculoskeletal trauma is incomplete muscle regeneration. Current therapies often fail to heal damaged muscle due to dysregulated healing programs and insufficient revascularization early in the repair process. There is a limited understanding of the temporal changes that occur during the early stages of muscle remodeling in response to engineered therapies. Previous work demonstrated that nanotopographically patterned scaffolds provide cytoskeletal guidance and direct endothelial angiogenic and anti-inflammatory phenotypes. The aim of this study was to evaluate how endothelial cell (EC) patterning guides temporal and histomorphological muscle remodeling after muscle injury. In the current study, mice were treated with EC-laden engineered constructs that exhibited either aligned or random patterning of collagen nanofibrils, following a volumetric muscle loss injury (VML). Remodeling was evaluated at 2, 7, and 21 days post injury. Over the 21-day study, all groups (Acellular Aligned, EC Aligned, EC Random) demonstrated similar significant increases in vascular density and myogenesis. Animals treated with acellular controls demonstrated a two-fold decrease in muscle cross-sectional area between days 2 and 21 post injury, consistent with VML-induced muscle atrophy; however, animals treated with patterned EC-laden constructs exhibited preservation of muscle mass. The implantation of an EC-laden construct led to a 50% increase in the number of animals exhibiting areas of fibrous remodeling adjacent to the construct, along with greater collagen deposition ( < 0.01) compared to acellular controls 21 days post injury. These findings suggest that nanotopographically patterned EC-laden constructs may guide early muscle-protective programs that support muscle mass retention through myo-vascular independent pathways.
严重肌肉骨骼创伤后的一个主要挑战是肌肉再生不完全。由于愈合程序失调和修复过程早期血管再生不足，目前的治疗方法常常无法治愈受损肌肉。对于工程治疗所引发的肌肉重塑早期阶段发生的时间变化，人们了解有限。先前的研究表明，具有纳米拓扑图案的支架可提供细胞骨架导向，并引导内皮细胞产生血管生成和抗炎表型。本研究的目的是评估内皮细胞（EC）图案化如何指导肌肉损伤后的时间性和组织形态学肌肉重塑。在本研究中，小鼠在遭受体积性肌肉损失损伤（VML）后，接受了载有EC的工程构建体治疗，这些构建体呈现出胶原纳米纤维的排列或随机图案化。在损伤后2天、7天和21天对重塑情况进行评估。在为期21天的研究中，所有组（无细胞排列组、EC排列组、EC随机组）的血管密度和成肌均有相似的显著增加。接受无细胞对照治疗的动物在损伤后第2天至第21天之间肌肉横截面积减少了两倍，这与VML诱导的肌肉萎缩一致；然而，接受图案化载有EC构建体治疗的动物肌肉质量得以保留。植入载有EC的构建体导致与构建体相邻出现纤维重塑区域的动物数量增加了50%，并且与损伤后21天的无细胞对照相比，胶原沉积更多（<0.01）。这些发现表明，具有纳米拓扑图案的载有EC的构建体可能通过肌血管独立途径引导早期肌肉保护程序，从而支持肌肉质量的保留。
