Wang Lin, Cao Lan, Shansky Janet, Wang Zheng, Mooney David, Vandenburgh Herman
School of Engineering and Applied Sciences and Wyss Institute, Harvard University, Cambridge, Massachusetts, USA; Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island, USA; Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Medical Research Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
School of Engineering and Applied Sciences and Wyss Institute, Harvard University, Cambridge, Massachusetts, USA.
Mol Ther. 2014 Aug;22(8):1441-1449. doi: 10.1038/mt.2014.78. Epub 2014 Apr 28.
Repair of injured skeletal muscle by cell therapies has been limited by poor survival of injected cells. Use of a carrier scaffold delivering cells locally, may enhance in vivo cell survival, and promote skeletal muscle regeneration. Biomaterial scaffolds are often implanted into muscle tissue through invasive surgeries, which can result in trauma that delays healing. Minimally invasive approaches to scaffold implantation are thought to minimize these adverse effects. This hypothesis was addressed in the context of a severe mouse skeletal muscle injury model. A degradable, shape-memory alginate scaffold that was highly porous and compressible was delivered by minimally invasive surgical techniques to injured tibialis anterior muscle. The scaffold controlled was quickly rehydrated in situ with autologous myoblasts and growth factors (either insulin-like growth factor-1 (IGF-1) alone or IGF-1 with vascular endothelial growth factor (VEGF)). The implanted scaffolds delivering myoblasts and IGF-1 significantly reduced scar formation, enhanced cell engraftment, and improved muscle contractile function. The addition of VEGF to the scaffold further improved functional recovery likely through increased angiogenesis. Thus, the delivery of myoblasts and dual local release of VEGF and IGF-1 from degradable scaffolds implanted through a minimally invasive procedure effectively promoted the functional regeneration of injured skeletal muscle.
细胞疗法修复受损骨骼肌受到注射细胞存活率低的限制。使用局部递送细胞的载体支架可能会提高体内细胞存活率，并促进骨骼肌再生。生物材料支架通常通过侵入性手术植入肌肉组织，这可能会导致创伤，从而延迟愈合。支架植入的微创方法被认为可以将这些不良反应降至最低。在严重的小鼠骨骼肌损伤模型中验证了这一假设。通过微创外科技术将一种可降解、具有形状记忆功能、高度多孔且可压缩的藻酸盐支架递送至受伤的胫前肌。该支架原位迅速与自体成肌细胞和生长因子（单独的胰岛素样生长因子-1（IGF-1）或IGF-1与血管内皮生长因子（VEGF））重新水化。植入递送成肌细胞和IGF-1的支架可显著减少瘢痕形成，增强细胞植入，并改善肌肉收缩功能。向支架中添加VEGF可能通过增加血管生成进一步改善功能恢复。因此，通过微创程序植入的可降解支架递送成肌细胞以及VEGF和IGF-1的双重局部释放有效地促进了受损骨骼肌的功能再生。
