Bioinspired electrospun decellularized extracellular matrix scaffolds promote muscle regeneration in a rat skeletal muscle defect model

Abstract

Volumetric muscle loss is a debilitating injury that can leave patients with long-lasting or permanent structural and functional deficits. With clinical treatments failing to address these shortcomings, there is a great need for tissue-engineered therapies to promote skeletal muscle regeneration. In this study, we aim to assess the potential for electrospun decellularized skeletal muscle extracellular matrix (dECM) to promote skeletal muscle regeneration in a rat partial thickness tibialis anterior defect model. Aligned electrospun scaffolds with varying degrees of crosslinking density were implanted into the defect site and compared to an empty defect control. After 8 weeks, muscles were harvested, weighed, and cellular and morphological analyses were performed via histology and immunohistochemistry. Cell infiltration, angiogenesis, and myogenesis were observed in the defect site in both dECM groups. However, favorable mechanical properties and slower degradation kinetics resulted in greater support of tissue remodeling in the more crosslinked scaffolds and preservation of existing myofiber area in both dECM groups compared to the empty defect control. More sustained release of proregenerative degradation products also promoted greater myofiber formation in the defect site. This study allowed for a greater understanding of how electrospun skeletal muscle scaffolds interact with existing skeletal muscle and can inform their potential as a therapy in a wide variety of soft tissue applications.

Cyclic freeze–thaw grinding to decellularize meniscus for fabricating porous, elastic scaffolds

“…17,67 In contrast, our dmECM scaffolds show moderate immune responses and might promote constructive tissue remodeling and regeneration. 68 Future studies should evaluate the long-term FBR responses to the dmECM scaffold and also assess its capacity to repair and regenerate the meniscus in situ.…”

Decellularized ECM hydrogels: prior use considerations, applications, and opportunities in tissue engineering and biofabrication

“…Skeletal musclederived dECM hydrogels have been shown in multiple studies to induce greater proliferation and differentiation of myosatel-lite cells than conventional 3D cultures in materials such as collagen or PCL. 221,288,289 Implantation of dECM hydrogels can promote healing processes of various muscle injuries by enabling cell infiltration, angiogenesis and myogenesis as demonstrated in animal models. 221 Greater myotube formation and increased activity of anti-inflammatory M2 macrophages has been observed in animals to which dECM scaffold was implanted in regions with volumetric muscle loss.…”

“…221,288,289 Implantation of dECM hydrogels can promote healing processes of various muscle injuries by enabling cell infiltration, angiogenesis and myogenesis as demonstrated in animal models. 221 Greater myotube formation and increased activity of anti-inflammatory M2 macrophages has been observed in animals to which dECM scaffold was implanted in regions with volumetric muscle loss. 221,289 Skeletal muscle, being a structural and load bearing tissue, benefits from the addition of various modifiers that can stiffen their native dECM.…”

“…218 dECM hydrogels have been used in conjunction with carrier polymers or on their own to produce bioactive scaffolds. 202,220,221 A mixture of porcine cardiac dECM hydrogel and polyethylene oxide (PEO) has been successfully used in electrospinning with hexafluoro-2-propanol (HFIP) as a solvent. After fabrication, the PEO was washed with aqueous medium leaving only the dECM hydrogel fibers.…”

“…202 In an animal study, they observed cell infiltration, angiogenesis and myogenesis in groups where electrospun dECM hydrogel scaffolds were implanted. 221 Electrospraying is a variation of electrospinning where the electric field applied to the nozzle containing the material forces its dispersion into droplets. 223 These can vary in range from hundreds of micrometers down to tens of nanometer.…”