Harnessing the potential of response surface methodology-based optimized scaffolds in volumetric muscle loss repair...

Volumetric Muscle Loss (VML) is a complex tissue injury characterised by loss of tissue beyond the body's intrinsic regenerative capacity, resulting in impaired muscle regeneration and functional recovery. Limited cellular proliferation and poor in situ healing make VML one of the most challenging issues in tissue engineering. Conventional approaches of acidic gelling and use of artificial substrates compromise the structural integrity, biocompatibility and functional performance of tissue-engineered constructs. Moreover, the irregular geometries of muscle defects make surgical reconstruction technically challenging and often insufficient to achieve complete functional restoration. In this study, a novel porous scaffold containing collagen, fibronectin, and raloxifene (a cell-proliferative drug) was prepared for VML repair. The concentration of scaffold components was optimized using Response Surface Methodology (RSM) to obtain an effective scaffold composition. The regenerative efficacy of the optimized scaffold was evaluated in a Sprague-Dawley rat model of VML. The results suggested that RSM-optimized scaffold significantly improved VML repair after 21 days (p < 0.05) in vivo. A prominent development of muscle fibre and deposition of collagen was observed. At molecular level, a significant increase in the expression of MyoD and STAT3 genes was observed in optimized scaffold group, suggesting enhanced myogenesis and tissue repair. The findings indicate that RSM may be utilized to optimize the tissue-engineered construct to improve VML repair.