Volumetric muscle loss (VML) is a loss of over ∼10% of muscle mass that results in functional impairment. Although skeletal muscle possesses the ability to repair and regenerate itself following minor injuries, VML injuries are irrecoverable. Currently, there are no successful clinical therapies for the treatment of VML. Previous studies have treated VML defects with decellularized extracellular matrix (D-ECM) scaffolds derived from either pig urinary bladder or small intestinal submucosa. These therapies were unsuccessful due to the poor mechanical stability of D-ECM leading to quick degradation in vivo. To circumvent these issues, in this manuscript aligned nanofibers of D-ECM were created using electrospinning that mimicked native muscle architecture and provided topographical cues to primary satellite cells. Additionally, combining D-ECM with polycaprolactone (PCL) improved the tensile mechanical properties of the electrospun scaffold. In vitro testing shows that the electrospun scaffold with aligned nanofibers of PCL and D-ECM supports satellite cell growth, myogenic protein expression, and myokine production.
Decellularization removes cellular antigens while preserving the ultrastructure and composition of extracellular matrix (ECM). Decellularized ECM (DECM) scaffolds have been widely used in various tissue engineering applications with varying levels of success. The mechanical, architectural and bioactive properties of a DECM scaffold depend largely on the method of decellularization and dictate its clinical efficacy. This article highlights the advantages and challenges associated with the clinical use of DECM scaffolds. Poor mechanical strength is a significant disadvantage of some DECM scaffolds in the repair of load-bearing tissues as well as critical-size defects, where long-term mechanical support is required for the regenerating tissue. Combining DECM scaffolds with synthetic biocompatible polymers could provide a useful strategy to circumvent the issues of poor mechanical stability. This article reviews studies that have combined DECM scaffolds from various tissues with synthetic polymers to create hybrid scaffolds using electrospinning. These hybrid scaffolds provide a mechanical backbone while retaining the bioactive properties of DECM, thus offering a significant advantage for tissue engineering and regenerative medicine applications.
Skeletal muscle is inept in regenerating after traumatic injuries due to significant loss of basal lamina and the resident satellite cells. To improve regeneration of skeletal muscle, we have developed biomimetic sponges composed of collagen, gelatin, and laminin (LM)-111 that were crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC). Collagen and LM-111 are crucial components of the muscle extracellular matrix and were chosen to impart bioactivity whereas gelatin and EDC were used to provide mechanical strength to the scaffold. Morphological and mechanical evaluation of the sponges showed porous structure, water-retention capacity and a compressive modulus of 590-808 kPa. The biomimetic sponges supported the infiltration and viability of C 2 C 12 myoblasts over 5 days of culture. The myoblasts produced higher levels of myokines such as VEGF, IL-6, and IGF-1 and showed higher expression of myogenic markers such as MyoD and myogenin on the biomimetic sponges. Biomimetic sponges implanted in a mouse model of volumetric muscle loss (VML) supported satellite, endothelial, and inflammatory cell infiltration but resulted in limited myofiber regeneration at 2 weeks post-injury.
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