Basurto Ivan M, Boudreau Ryann D, Bandara Geshani C, Muhammad Samir A, Christ George J, Caliari Steven R
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22903.
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903.
bioRxiv. 2024 Sep 3:2024.08.30.610194. doi: 10.1101/2024.08.30.610194.
Volumetric muscle loss (VML) injuries are characterized by the traumatic loss of skeletal muscle resulting in permanent damage to both tissue architecture and electrical excitability. To address this challenge, we previously developed a 3D aligned collagen-glycosaminoglycan (CG) scaffold platform that supported myotube alignment and maturation. In this work, we assessed the ability of CG scaffolds to facilitate functional muscle recovery in a rat tibialis anterior (TA) model of VML. Functional muscle recovery was assessed following implantation of either non-conductive CG or electrically conductive CG-polypyrrole (PPy) scaffolds at 4, 8, and 12 weeks post-injury by electrical stimulation of the peroneal nerve. After 12 weeks, scaffold-treated muscles produced maximum isometric torque that was significantly greater than non-treated tissues. Histological analysis further supported these reparative outcomes with evidence of regenerating muscle fibers at the material-tissue interface in scaffold-treated tissues that was not observed in non-repaired muscles. Scaffold-treated muscles possessed higher numbers of M1 and M2 macrophages at the injury while conductive CG-PPy scaffold-treated muscles showed significantly higher levels of neovascularization as indicated by the presence of pericytes and endothelial cells, suggesting a persistent wound repair response not observed in non-treated tissues. Finally, only tissues treated with non-conductive CG scaffolds displayed neurofilament staining similar to native muscle, further corroborating isometric contraction data. Together, these findings show that CG scaffolds can facilitate improved skeletal muscle function and endogenous cellular repair, highlighting their potential use as therapeutics for VML injuries.
容积性肌肉损失（VML）损伤的特征是骨骼肌受到创伤性损失，导致组织结构和电兴奋性均受到永久性损害。为应对这一挑战，我们之前开发了一种三维排列的胶原-糖胺聚糖（CG）支架平台，该平台可支持肌管排列和成熟。在这项研究中，我们评估了CG支架在大鼠胫骨前肌（TA）VML模型中促进功能性肌肉恢复的能力。在损伤后4周、8周和12周，通过电刺激腓总神经，对植入非导电CG或导电CG-聚吡咯（PPy）支架后的功能性肌肉恢复情况进行评估。12周后，接受支架治疗的肌肉产生的最大等长扭矩明显大于未治疗的组织。组织学分析进一步支持了这些修复结果，在接受支架治疗的组织中，材料-组织界面处有再生肌纤维的证据，而在未修复的肌肉中未观察到这一现象。在损伤部位，接受支架治疗的肌肉拥有更多数量的M1和M2巨噬细胞，而接受导电CG-PPy支架治疗的肌肉显示出明显更高的新生血管化水平，周细胞和内皮细胞的存在表明了这一点，这表明在未治疗的组织中未观察到持续的伤口修复反应。最后，只有接受非导电CG支架治疗的组织显示出与天然肌肉相似的神经丝染色，进一步证实了等长收缩数据。总之，这些发现表明CG支架可以促进骨骼肌功能的改善和内源性细胞修复，突出了其作为VML损伤治疗方法的潜在用途。
