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

Abstract

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.

Adipose Mesenchymal Stem Cell Derived Exosomes Promote Keratinocytes and Fibroblasts Embedded in Collagen/Platelet‐Rich Plasma Scaffold and Accelerate Wound Healing

“…The important role of immune microenvironment in wound healing should also be considered. Yuan et al [54] designed a hydrogel that packaged engineered small extracellular vesicles (sEVs) and applied them to diabetic wounds, showing that sustained release of sEVs induced macrophages to switch from M1 to M2 phenotype and thereby exert prohealing effects throughout the inflammation and proliferation stages of diabetic wound healing. In our study, the ADSC-exos loaded in the COL/PRP scaffold material can play a similar effect through sustained release.…”

Reactive Oxygen Species‐Scavenging Nanosystems in the Treatment of Diabetic Wounds

“…Therefore, we constructed a whole‐course‐repair system by a nanosystem‐enriched hydrogel to concurrently gain a mutually supportive cycle of neurogenesis–angiogenesis. [ 121 ] This hydrogel can be in situ locally injected to cover wounds long‐term for facilitated healing via the synergistic effect of Mg 2+ and engineered sEVs. During the inflammation phase, this system can effectively induce MSCs toward neurogenic differentiation, meanwhile providing a beneficial immune microenvironment for tissue repair.…”

“…The preparation of this hydrogel needed only one step by mixing the solution of HA-ADH/Mg and the solution of OSA in equal volume. Reproduced with permission [121]. Copyright 2023, Wiley-VCH.…”

Dynamical Integration of Antimicrobial, Anti‐Inflammatory, and Pro‐Osteogenic Activities on Polyetheretherketone via a Porous N‐Halamine Polymeric Coating

“…Macrophage polarization could be regulated by a variety of factors of implant surface, including chemical components, stiffness, elastic modulus, and topography, which either promote or mitigate macrophage polarization and thereby influence the outcomes of osteogenesis and angiogenesis. [50][51][52][53][54] In particular, the surface topography can effectively control the cellular behaviors of macrophages around implants. The hydrophilic or neutral surfaces tend to inhibit the adhesion and activation of macrophages and create an anti-inflammatory microenvironment, and the porous surfaces tend to inhibit M1 polarization of macrophages.…”