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...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)cross-linked 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.展开更多
基金NIH R03AR068108,NIH R01AR071649 and Purdue Start-up Package is greatly appreciated.The authors acknowledge the use of Purdue Life Science Microscopy Facility,Purdue Histology Core Facility.The authors also acknowledge the use of facilities of the Bindley Bioscience Center,a core facility of the NIH-funded Indiana Clinical and Translational Sciences Institute.
文摘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)cross-linked 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.
