Xenogeneic Extracellular Matrix as an Inductive Scaffold for Regeneration of a Functioning Musculotendinous Junction

The prevailing dogma in tissue engineering is cell-centric. One shortcoming of this approach is the failure to provide the implanted cells with a suitable in vivo microenvironment that promotes tissue reconstruction. Extracellular matrix (ECM)-based scaffolds provide a three-dimensional microenvironment that can promote constructive and functional tissue remodeling rather than inflammation and scarring even in the absence of any implanted cells. The objective of this study was to determine the ability of an ECM-based scaffold to facilitate functional restoration of the distal gastrocnemius musculotendinous junction in a canine model after complete resection of the tissue. Within 6 months, vascularized, innervated skeletal muscle that was similar to normal muscle tissue had formed at the ECM-scaffold implantation site. This neo-tissue generated 48% of the contractile force of contralateral musculotendinous junction and represents the first report of de novo formation of contractile, vascularized, and innervated skeletal muscle in situ after significant tissue loss.