A Whole-Course-Repair System Based on Neurogenesis-Angiogenesis Crosstalk and Macrophage Reprogramming Promotes Diabetic Wound Healing

作者：Xiong, Yuan; Lin, Ze; Bu, Pengzhen; Yu, Tao; Endo, Yori; Zhou, Wu; Sun, Yun; Cao, Faqi; Dai, Guandong; Hu, Yiqiang; Lu, Li; Chen, Lang; Cheng, Peng; Zha, Kangkang; Shahbazi, Mohammad-Ali^*; Feng, Qian^*; Mi, Bobin^*; Liu, Guohui^*

来源：Advanced Materials, 2023, 35(19).

DOI：10.1002/adma.202212300

• angiogenesis
• diabetic wounds
• hydrogels
• macrophages
• neurogenesis

Diabetic wound (DW) therapy is currently a big challenge in medicine and strategies to enhance neurogenesis and angiogenesis have appeared to be a promising direction. However, the current treatments have failed to coordinate neurogenesis and angiogenesis simultaneously, leading to an increased disability rate caused by DWs. Herein, a whole-course-repair system is introduced by a hydrogel to concurrently achieve a mutually supportive cycle of neurogenesis-angiogenesis under a favorable immune-microenvironment. This hydrogel can first be one-step packaged in a syringe for later in situ local injections to cover wounds long-termly for accelerated wound healing via the synergistic effect of magnesium ions (Mg2+) and engineered small extracellular vesicles (sEVs). The self-healing and bio-adhesive properties of the hydrogel make it an ideal physical barrier for DWs. At the inflammation stage, the formulation can recruit bone marrow-derived mesenchymal stem cells to the wound sites and stimulate them toward neurogenic differentiation, while providing a favorable immune microenvironment via macrophage reprogramming. At the proliferation stage of wound repair, robust angiogenesis occurs by the synergistic effect of the newly differentiated neural cells and the released Mg2+, allowing a regenerative neurogenesis-angiogenesis cycle to take place at the wound site. This whole-course-repair system provides a novel platform for combined DW therapy.

• 单位
  1; 南方医科大学; 华中科技大学; 上海交通大学; 重庆大学