Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers

Abstract

A diabetic foot ulcer (DFUs) is a state of prolonged chronic inflammation, which can result in amputation. Different from normal skin wounds, various commercially available dressings have not sufficiently improved the healing of DFUs. In this study, a novel self-healing hydrogel was prepared by in situ crosslinking of N-carboxyethyl chitosan ( N-chitosan) and adipic acid dihydrazide (ADH) with hyaluronic acid-aldehyde (HA-ALD), to provide a moist and inflammatory relief environment to promote stem cell proliferation or secretion of growth factors, thus accelerating wound healing. The results demonstrated that this injectable and self-healing hydrogel has excellent swelling properties, stability, and mechanical properties. This biocompatible hydrogel stimulated secretion of growth factors from bone marrow mesenchymal stem cells (BM-MSCs) and regulated the inflammatory environment by inhibiting the expression of M1 macrophages and promoting the expression of M2 macrophages, resulting in granulation tissue formation, collagen deposition, nucleated cell proliferation, neovascularization, and enhanced diabetic wound healing. This study showed that N-chitosan/HA-ALD hydrogel could be used as a multifunctional injectable wound dressing to regulate chronic inflammation and provide an optimal environment for BM-MSCs to promote diabetic wound healing.

Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation

“…Another approach to increase growth factors is to provide bone-marrow mesenchymal stem cells (BM-MSCs). Bai et al developed an injectable hydrogel made from crosslinking N-chitosan and adipic acid dihydrazide with hyaluronic acid-aldehyde to deliver BM-MSCs into the wound bed (250). In vitro and in vivo investigations in diabetic wound healing showed that the hydrogel was able to stimulate BM-MSC-derived secretion of TGF-b1, VEGF, and FGF-2 as well as inhibiting chronic inflammation through M2 macrophage polarization (250).…”

“…Bai et al developed an injectable hydrogel made from crosslinking N-chitosan and adipic acid dihydrazide with hyaluronic acid-aldehyde to deliver BM-MSCs into the wound bed (250). In vitro and in vivo investigations in diabetic wound healing showed that the hydrogel was able to stimulate BM-MSC-derived secretion of TGF-b1, VEGF, and FGF-2 as well as inhibiting chronic inflammation through M2 macrophage polarization (250). It also induced granulation tissue formation, collagen deposition, tissue vascularization, and improved wound closure (250).…”

“…In vitro and in vivo investigations in diabetic wound healing showed that the hydrogel was able to stimulate BM-MSC-derived secretion of TGF-b1, VEGF, and FGF-2 as well as inhibiting chronic inflammation through M2 macrophage polarization (250). It also induced granulation tissue formation, collagen deposition, tissue vascularization, and improved wound closure (250). The LeucoPatch uses a similar approach to promote healing.…”

Multifunctional bioactive core-shell electrospun membrane capable to terminate inflammatory cycle and promote angiogenesis in diabetic wound

“…Prolonged inflammation is the ultimate cause of delayed DW healing [ 71 ]. One of the key bioactivities features desired for an active wound dressing is the anti-inflammatory effect.…”

3D Printing of Dual-cell Delivery Titanium Alloy Scaffolds for Improving Osseointegration Through Enhancing Angiogenesis and Osteogenesis

“…Bone marrow mesenchymal stem cells (BMSC) is widely used as seed cells in tissue engineering and regenerative medicine [10]. A series of researches have indicated that BMSC have great potential for enhancing the repair of bone defects, owing to its high capacity for self-renewal and multi differentiation potential.…”