Extracellular Matrix-Mimetic Intrinsic Versatile Coating Derived from Marine Adhesive Protein Promotes Diabetic Wound Healing through Regulating the Microenvironment
Lulu Wang, Xue Bo, Xin Zhang, Yahui Gao, Pingping Xu, Bohua Dong, Lujia Zhang, Lei Zhang, Lin Li, Weizhi Liu
Abstract
The management of diabetic wound healing remains a severe clinical challenge due to the complicated wound microenvironments, including abnormal immune regulation, excessive reactive oxygen species (ROS), and repeated bacterial infections. Herein, we report an extracellular matrix (ECM)-mimetic coating derived from scallop byssal protein (Sbp9 Δ ), which can be assembled in situ within 30 min under the trigger of Ca 2+ driven by strong coordination interaction. The biocompatible Sbp9 Δ coating and genetically programmable LL37-fused coating exhibit outstanding antioxidant, antibacterial, and immune regulatory properties in vitro . Proof-of-concept applications demonstrate that the coating can reliably promote wound healing in animal models, including diabetic mice and rabbits, ex vivo human skins, and Staphylococcus aureus -infected diabetic mice. In-depth mechanism investigation indicates that improved wound microenvironments accelerated wound repair, including alleviated bacterial infection, lessened inflammation, appearance of abundant M2-type macrophages, removal of ROS, promoted angiogenesis, and re-epithelialization. Collectively, our investigation provides an in situ, convenient, and effective approach for diabetic wound repair.