Naturally occurring porcine-derived extracellular matrix (ECM) has successfully been used as a biological scaffold material for site-specific reconstruction of a wide variety of tissues. The site-specific remodelling process includes rapid degradation of the scaffold, with concomitant recruitment of mononuclear, endothelial and bone marrow-derived cells, and can lead to the formation of functional skeletal and smooth muscle tissue. However, the temporal and spatial patterns of innervation of the remodelling scaffold material in muscular tissues are not well understood. A retrospective study was conducted to investigate the presence of nervous tissue in a rat model of abdominal wall reconstruction and a canine model of oesophageal reconstruction in which ECM scaffolds were used as inductive scaffolds. Evidence of mature nerve, immature nerve and Schwann cells was found within the remodelled ECM at 28 days in the rat body wall model, and at 91 days post surgery in a canine model of oesophageal repair. Additionally, a microscopic and morphological study that investigated the response of primary cultured neurons seeded upon an ECM scaffold showed that neuronal survival and outgrowth were supported by the ECM substrate. Finally, matricryptic peptides resulting from rapid degradation of the ECM scaffold induced migration of terminal Schwann cells in a concentration-dependent fashion in vitro. The findings of this study suggest that the reconstruction of tissues in which innervation is an important functional component is possible with the use of biological scaffolds composed of extracellular matrix.