Bioactivity of small intestinal submucosa and oxidized regenerated cellulose/collagen

Abstract

Objective: This study examined the bioactivity of porcine small intestinal submucosa (SIS Wound Matrix [SISWM], USP) and oxidized regenerated cellulose/collagen (ORC).

Design: Bioactivity was assessed in vitro as the ability to stimulate neurite outgrowth in rat pheochromocytoma (PC12) cells, proliferation of human fibroblasts, secretion of vascular endothelial growth factor (VEGF) from human fibroblasts, and in an in vivo angiogenesis model. In the angiogenesis model, SISWM and ORC were implanted subcutaneously into the mice, and vessel ingrowth was assessed at day 21 after implantation using fluorescence microangiography and histology.

Main outcome measures: The change in cellular differentiation, proliferation, growth factor secretion, and angiogenesis over the negative control was measured after exposure to SISWM or ORC.

Main results: SISWM increased neurite outgrowth in PC12 cells by approximately 22% over negative controls and induced proliferation in 50.8% of human fibroblasts. These increases were comparable to positive controls. ORC was not active in either of these assays. SISWM also stimulated fibroblast VEGF secretion to a greater extent (422.4 pg/mL) than ORC (4.2 pg/mL) (P < .001). At 21 days, fluorescence microangiography showed dense infiltration of blood vessels in the SISWM that extended approximately 3 mm from the edge of the disc. In contrast, the ORC implant showed blood vessel incursion less than 1 mm from the edge of the disc, and it dissolved in the site.

Conclusions: SISWM shows much greater bioactivity than ORC. This is likely related to its close structural and biochemical approximation to natural dermal extracellular matrix and may help explain the strong clinical successes of SISWM.