期刊
BIOACTIVE MATERIALS
卷 6, 期 4, 页码 1201-1213出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2020.10.012
关键词
Hyaluronic acid; Chondroitin sulfate; Hydrogels; Volumetric muscle loss; Myoblasts; Skeletal muscle tissue engineering
资金
- NIH [R03AR068108, R01AR071649]
- NIH
Optimizing the biophysical properties of HA-CS hydrogels can promote skeletal muscle regeneration in VML injuries in mice, supporting implant integration with host tissue and facilitating satellite cell migration, myofiber formation, angiogenesis, and innervation with reduced scar tissue formation in vivo. Hydrogel-treated mice showed functional improvements comparable to autograft-treated mice as early as 1 week post-implantation.
Volumetric muscle loss (VML) injuries characterized by critical loss of skeletal muscle tissues result in severe functional impairment. Current treatments involving use of muscle grafts are limited by tissue availability and donor site morbidity. In this study, we designed and synthesized an implantable glycosaminoglycan-based hydrogel system consisting of thiolated hyaluronic acid (HA) and thiolated chondroitin sulfate (CS) crosslinked with poly(ethylene glycol) diacrylate to promote skeletal muscle regeneration of VML injuries in mice. The HA-CS hydrogels were optimized with suitable biophysical properties by fine-tuning degree of thiol group substitution to support C2C12 myoblast proliferation, myogenic differentiation and expression of myogenic markers MyoD, MyoG and MYH8. Furthermore, in vivo studies using a murine quadriceps VML model demonstrated that the HA-CS hydrogels supported integration of implants with the surrounding host tissue and facilitated migration of Pax7(+) satellite cells, de novo myofiber formation, angiogenesis, and innervation with minimized scar tissue formation during 4-week implantation. The hydrogel-treated and autograft-treated mice showed similar functional improvements in treadmill performance as early as 1-week post-implantation compared to the untreated groups. Taken together, our results demonstrate the promise of HA-CS hydrogels as regenerative engineering matrices to accelerate healing of skeletal muscle injuries.
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