Nerve-specific extracellular matrix hydrogel promotes functional regeneration following nerve gap injury.

Nerve transection requires surgical intervention to restore function. The standard of care involves coaptation when a tension-free repair is achievable, or interposition of a graft or conduit when a gap remains. Despite advances, nerve gap injury is associated with unsatisfactory recovery. This study investigates the use of a decellularized, porcine nerve-derived hydrogel filler (peripheral nerve matrix, PNM) for conduits in an 8 mm rat sciatic nerve gap model. The decellularized tissue maintained multiple nerve-specific matrix components and nerve growth factors. This decellularized tissue was used to formulate hydrogels, which were deployed into conduits for nerve gap repair. Nerve recovery was assessed up to 24 weeks post injury by gait analysis, electrophysiology, and axon counting. Deployment of PNM within conduits was shown to improve electrophysiologic response and axon counts compared with those of empty conduit controls. These results indicate that PNM has potential benefits when used as a filler for conduits in nerve gap injuries.

Free radical-decellularized tissue promotes enhanced antioxidant and anti-inflammatory macrophage response.

Oxidative stress leads to the progression of many diseases including chronic wounds, atherosclerosis, stroke and cancer. The modification of biomolecules with reactive nitrogen or oxygen species has been shown to trigger oxidative stress pathways that are beneficial for healing. Extracellular matrix scaffolds have been used successfully in reconstructive applications due to the beneficial host response they induce. To tailor extracellular matrix scaffolds to enhance antioxidant response, ECM were prepared using reactive nitrogen or oxygen species. These scaffolds were shown to be effectively decellularized and possess oxidative or nitroxidative protein modifications. Macrophage responses in vitro and in an in vivo muscle injury model were shown to have enhanced antioxidant phenotypes without impairment of long-term remodeling. These observations suggest that ECM decellularized with reactive oxygen or nitrogen species could provide better outcomes for the treatment of ischemic diseases.