Rutin encapsulated decellularized earthworm granulation hydrogel promotes angiogenesis in wound healing of diabetic rabbit model by inhibiting TRAF1/NF-κB pathway

Abstract

Diabetic micro-vasculopathy is induced by accumulation of Reactive Oxygen Species (ROS) which results in delayed wound healing under hyperglycemic conditions. The classical practice of treating diabetic wound includes surgical debridement, hyperbaric oxygen therapy and use of antibiotics to control infection. The therapeutic interventions based on these classical practices have been found ineffective in management of diabetic wound healing and diabetic vasculopathy. Henceforth, engineered biomaterials with anti-oxidant activity have become research hotspots for their high biological activity, due to sustained release of active principles and weak immunogenicity. Based on these postulates, current study was conducted to evaluate diabetic wound healing potential of Rutin encapsulated decellularized earthworm granulation tissue (RdECM) with special reference on angiogenesis. The angiogenetic activity of RdECM was evaluated on cell line under hyperglycemic conditions and we found significant decline in ROS induced Deoxyribonucleic acid (DNA) damage and inhibition of Nuclear factor kappa B (NF-Kβ) pathway with subsequent aggregation of cells in tubular structure. Application of RdECM on diabetic wound resulted in accelerated wound healing, reduction in ROS induced DNA damage and down regulation of TNF receptor associated factor 1 (TRAF1). These changes results in inhibition of TRAF1-mediated NF-κB signal activation and subsequently angiogenesis in hyperglycemic conditions of diabetic wound. These findings support therapeutic utility of RdECM as angiogenetic agent and its potential use against diabetic wound healing.