Smart thermosensitive poloxamer hydrogels loaded with Nr-CWs for the treatment of diabetic wounds.

Abstract

The treatment of diabetic wound is a focus issue. At present, the Nocardia rubra cell wall skeleton (Nr-CWS) has been proved proven to promote angiogenesis and wound repair. Unfortunately, the high-glucose diabetic wound environment makes many drugs unable to be released effectively, and soon be removed. Smart thermosensitive poloxamer hydrogel (TH) is an ideal and adjustable drug delivery platform compatible with most living tissues. Here, a multifunctional composite thermosensitive hydrogel was developed. A mixture of poloxamers 407 and 188 as the gel matrix, and then it was physically mixed with Nr-CWS. The delivery vehicle not only controlled its release stably, preventing degradation in vitro, but also showed good affinity in vitro. In vivo, compared with thermosensitive poloxamer hydrogel alone or the direct use of Nr-CWS, the thermosensitive poloxamer hydrogel loaded with Nr-CWS promoted the proliferation of vascular endothelial cells effectively, resulting in increased expression of derma-related structural proteins and enhanced angiogenesis and wound healing. This study indicated that the angiogenesis and skin regeneration brought by Nr-CWS hydrogel are related to the activation of phosphatidylinositol 3 kinase and protein kinase B, Janus kinase/signal transducer and activator of transcription, and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways.