Pre-clinical evaluation of thermosensitive decellularized adipose tissue/platelet-rich plasma interpenetrating polymer network hydrogel for wound healing

Wound healing remains a challenge worldwide, and an ideal wound dressing that promotes healing is urgently needed. In this study, we developed a thermosensitive injectable hydrogel known as the thermosensitive decellularized adipose tissue/platelet-rich plasma interpenetrating polymer network (t-DPI) hydrogel based on decellularized adipose tissue (DAT) and temperature-controlled platelet-rich plasma (t-PRP). Abundant platelets, growth factors (GFs), and bioactive substances from the decellularized extracellular matrix (dECM) in the t-DPI hydrogel had positive effects on wound healing. The morphology, thermosensitivity, and GFs release properties of the t-DPI hydrogel were studied. In vitro, the t-DPI hydrogel showed ideal cytocompatibility and the abilities to promote the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, M2 macrophage polarization was enhanced after treated with t-DPI hydrogel. In vivo, the t-DPI hydrogel notably accelerated the full-thickness wound healing. The positive role of the t-DPI hydrogel on pro-angiogenesis, macrophage polarization and collagen deposition were validated in the nude mouse full-thickness skin defect model. In addition, the clinical application potential was confirmed using a pre-clinical porcine full-thickness wound model. Overall, this study demonstrated that the t-DPI hydrogel achieves fast and ideal wound healing in full-thickness wound defects and provides a potential clinical treatment strategy.