In vitro cellular response to oxidized collagen-PLLA hybrid scaffolds designed for the repair of muscular tissue defects and complex incisional hernias

摘要

Unique poly(L-lactic acid) (PLLA)-based scaffolds were constructed by embedding knitted PLLA yarns within a bioresorbable and differentially crosslinked three-dimensional (3D) oxidized collagen scaffold. The scaffolds were designed specifically for the repair of complex incisional abdominal wall hernias and the repair of defects within planar muscular tissues, such as the bladder. The chemical composition of the collagen matrix and the percentage of scaffold infiltration were compared for the different scaffold compositions. The results demonstrate that the incorporation of the collagen sponge within the PLLA scaffold facilitated bladder smooth muscle cell (bSMC) adhesion and proliferation. The highest dose of oxidized collagen (Oxicol) demonstrated better cell adhesion, resulting in the largest cell densities and most uniform distribution throughout the 3D collagen sponge. This formulation promoted the greatest alpha-smooth muscle actin (alpha SMA) expression detected through immunohistochemical staining and western blotting. For abdominal wall repair applications, the proliferation and differentiation of C2C12 myoblasts and myotube formation were studied. Following 7 days of myogenic induction, the greatest expression of mRNA of the myogenic markers myogenin and MRF4 was observed within the scaffolds with the highest dose of oxidized collagen, 1.5-and 3.85-fold greater expressions, respectively, compared to PLLA with unmodified collagen. Furthermore, in vitro myotube formation and MyMC expression were enhanced in the Oxicol scaffolds. We conclude that the Oxicol scaffold formulation with a high-dose oxidized collagen ratio provides enhanced myogenesis and alpha SMA, and the biological induction cues necessary to achieve better tissue integration, than standard PLLA scaffolds in the treatment of complex abdominal wall hernias. Copyright (C) 2013 John Wiley & Sons, Ltd.