Bioengineered cell-constructs using decellularized fish skin-based composite bioink for regenerating muscle tissue

Abstract

A biocomposite for enhancing muscle tissue regeneration was introduced using decellularized fish skins. Decellularized tilapia and cod skin were explored as constituents of the composite and compared with the conventionally used decellularized extracellular matrix (dECM) derived from porcine skin tissue. As a cell-laden bioink for 3D bioprinting, the choice of tilapia skin dECM, which possesses remarkable printability, allows for precise three-dimensional (3D) structure fabrication. Meanwhile, cod skin dECM was selected as the dispersed phase for enhancing biological activities because of its omega-3 unsaturated fatty acid, which is known to promote angiogenesis and is crucial for nutrient supply during tissue regeneration and lower inflammation. Through meticulous compositional optimization of the fish skin dECMs, efficient printability and high myogenic activity of the fish skin dECM composite were attained. In vitro evaluations using adipose stem cells clearly demonstrated the support of the cell-laden composite bioink for myogenesis, as determined by various cellular activities, including myogenic genes, compared to those of the porcine-based dECM bioink. The regenerative potential of the composites was validated using an in vivo mouse model of volumetric muscle loss. Based on these results, this study provides valuable insights into the use of decellularized fish skin as composite biomaterials and demonstrates their distinct advantages in muscle tissue engineering, in terms of both printability and bioactivity induction.