Minimally invasive approach to the repair of injured skeletal muscle with a shape-memory scaffold.
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.
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.
Lin
L
Wang
School of Engineering and Applied Sciences and Wyss Institute, Harvard University, Cambridge, Massachusetts, USA.
Lan
L
Cao
Myomics, Providence, Rhode Island, USA.
Janet
J
Shansky
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.
Zheng
Z
Wang
School of Engineering and Applied Sciences and Wyss Institute, Harvard University, Cambridge, Massachusetts, USA.
David
D
Mooney
School of Engineering and Applied Sciences and Wyss Institute, Harvard University, Cambridge, Massachusetts, USA; Myomics, Providence, Rhode Island, USA; Department of Pathology, Brown Medical School-Miriam Hospital, Providence, Rhode Island, USA. Electronic address: Vandenburghlab@gmail.com.
Herman
H
Vandenburgh
D000464:Alginates / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000293:injuries* / Q000503:physiopathology / Q000601:surgery*; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D017695:Soft Tissue Injuries / Q000628:therapy; D054457:Tissue Scaffolds / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D042461:Vascular Endothelial Growth Factor A; C519530:insulin-like growth factor-1, mouse; C467480:vascular endothelial growth factor A, mouse; D007334:Insulin-Like Growth Factor I; D020723:Glucuronic Acid