Anti-fibrotic properties of a decellularized extracellular matrix scaffold from porcine small intestinal submucosa are evident in normal human and keloid fibroblasts

Abstract

Abstract Uncontrolled fibrosis via excess deposition of extracellular matrix (ECM), is a hallmark of hypertrophic scars and keloids. A decellularized ECM biomaterial from porcine small intestinal submucosa (SIS; Biodesign® or BioD, Cook Biotech, Inc.), is widely used in clinical applications for tissue repair. The current study tested the effects of BioD scaffolds, as compared with collagen constructs, on normal human skin (nFB) and keloid fibroblasts (kFB). Real-time qPCR, ELISA, and knockdown studies were performed to study pro-fibrotic pathways in cultured cells. ECM gene expression array revealed that BioD significantly attenuated (p < 0.05) the expression of thrombospondin-1 and fibronectin-1, two drivers of fibrosis in nFB as well as kFB. BioD repressed thrombospondin-1 and fibronectin-1 gene expression manifested as significant downregulation (n = 5–6; p < 0.05) of both proteins in nFB and kFB. The levels of latent transforming growth factor (LAP-TGFβ-1) were markedly reduced (n = 5; p < 0.05) in both nFB and kFB following treatment with BioD but not the other constructs. Knockdown of FN1 using siRNA significantly attenuated (n = 5, p < 0.05) pro-fibrotic responses including expression of Col1A1 and the levels of LAP-TGFβ-1 in nFB suggesting downregulation of FN1 by BioD is one of the primary underlying mechanisms of attenuated pro-fibrotic responses in keloid fibroblasts.