Non-Immunogenic Structurally and Biologically Intact Tissue Matrix Grafts for the Immediate Repair of Ballistic-Induced Vascular and Nerve Tissue Injury in Combat Casualty Care

摘要

Produce decellularized and freeze-dried umbilical vessel grafts to serve as off-the-shelf vascular graft prostheses for below-the-knee vassal replacement, AV access, and other clinically relevant applications. Procedures for procurement, dissection, and processing of human umbilical veins, including decallularization and cryo or solution preservation, were optimized. The umbilical artery was found unsuitable for use. Veins were Successfully processed with rhDNase instead of bovine DNase, and gamma irradiated to reduce the risk of disease transmission. Processed veins were found to maintain matrix structural integrity, biomechanical properties and were biocompatible and biologically active. Umbilical vein grafts were evaluated acutely in viva as arterio- venous shunts in both pigs and dogs and were easily accessed with needle despite their anatomical coiling. When grafts were implanted in the Same porcine model for a 12-day period, they remained palpable and 100% patent under high flow conditions. In addition, the lumen re-endothelialized in central areas of the grafts despite a significant cross-species inflammatory response. To limit cross-species immune issues a non-human primate model was developed and used to demonstrate patency and healing of the vein graft up to 6 weeks as an arterio-venous shunt.