Necrosis reduction efficacy of subdermal biomaterial mediated oxygen delivery in ischemic skin flaps

Abstract

AbstractInadequate tissue blood supply (e.g., in a wound or a poorly vascularised graft) can result in tissue ischemia and necrosis. As revascularization is a slow process relative to the proliferation of bacteria and the onset and spread of tissue necrosis, extensive tissue damage and loss can occur. Necrosis can spread rapidly, and treatment options are limited such that loss of tissue in ischemic tissue following necrosis onset is considered unavoidable and irreversible.Oxygen delivery from biomaterials exploiting aqueous decomposition of peroxy-compounds has shown some potential in overcoming the supply limitations caused by quite short oxygen diffusion distances in tissues by creating higher concentration gradients than can be attained by air saturated solutions or by distributing oxygen supply throughout a scaffold or construct by using particulate formulations. These have found application in tissue preservation, bioinks, creation of 3D tissue analogues etc. In preclinical models among the more exciting reports was a single study demonstrating reduction of ischemic skin necrosis albeit only short term using short term sub dermal delivery of oxygen below ischemic skin flaps. To explore this effect further, we developed an implantable solid peroxide-biomaterial based system with reduced hydrogen peroxide release by virtue of incorporation of minerals to catalytically decompose it in a much longer flap than examined previously. Blood flow in this flap reduced from essentially normal to essentially zero, along its 9cm length. Without treatment ∼50% of the total flap was necrotic in 2-4 days. In both groups, complete necrosis in the distal third of the flap with no observable flood flow was observed. But in the middle low blood flow region of the flap, treatment did prevent necrosis. This study indicated that subdermal oxygen delivery alone cannot completely mitigate dermal necrosis if no blood flow is present, but it could improve the survival of partially tissue at least in the short term which could find application to augment conventional treatments or to gain time until surgical intervention.