Photoresponsive Blood-Derived Protein Hydrogels Packed with Bioactive Carbon Dots Modulate Mitochondrial Homeostasis and Reprogram Metabolism for Chronic Wound Healing in Diabetes
Sicong Ren, Huixin Lv, Sheng Chen, Jing Zhou, Siyu Chen, Jingxia Chen, Jiaxin Luo, Yuanxin Guo, Huan Wang, Jingjie Zhai, Yanmin Zhou
Abstract
Autologous platelet concentrates (APC) represent a class of personalized regenerative materials for vascularized tissue regeneration. However, shortcomings including poor controllability of gel formation, lack of reactive oxygen species (ROS) scavenging ability, and deficient anti-inflammatory capacity restrict the tissue healing outcomes of APC. This study proposes an APC-based synergistic platform (CurCDs@iPRF-MA) for the treatment of chronic wounds in diabetes. Such a platform is composed of injectable platelet-rich fibrin (iPRF), gelatin methacryloyl (GelMA), and a carbogenic nanodrug from curcumin (CurCDs) that is injectable before the light-induced gel formation process, greatly facilitating the clinical applications of APC. Significantly, CurCDs@iPRF-MA can modulate the mitochondrial homeostasis under inflammatory conditions, activate the oxidative phosphorylation (OXPHOS) program, and regulate the diabetic microenvironment through metabolic reprogramming to achieve macrophage phenotype regulation and ROS elimination, as well as promote vascularization by releasing autologous growth factors, dramatically improving the healing efficacy of the chronic wounds in diabetes. This study offers a practical and effective approach to developing spatiotemporally controllable and multifunctional APC-based hydrogels for highly effective tissue regeneration.