Injectable Hypoxia-Induced Conductive Hydrogel to Promote Diabetic Wound Healing

Abstract

Injectable hydrogels with the capability to cast a hypoxic microenvironment is of great potentialities to develop novel therapies for tissue regeneration. However, the relative research still remains at the conceptual phase. Herein, we chose diabetic wound as a representative injury model to explore the actual therapeutic results of tissue injury by injectable hypoxiainduced hydrogels. To enhance recovery and widen applicability, the hypoxia-induced system was incorporated with a conductive network by an original sequentially interpenetrating technique based on the combination of a fast "click chemistry" and a slow enzymatic mediated cross-linking. Hyperbranched poly(β-amino ester)-tetraaniline (PBAE-TA) was cross-linked with thiolated hyaluronic acid (HA-SH) via a thiol−ene click reaction, contributing to the rapid formation of the first conductive network, where vanillin-grafted gelatin (Geln-Van) and laccase (Lac) with a slow cross-linking rate were employed in casting a hypoxic microenvironment. The as-prepared injectable hydrogels possessed both suitable conductivity and sustainable hypoxia-inducing capability to upregulate the hypoxia-inducible factor-1α and connexin 43 expressions of the encapsulated adipose-derived stem cells, which enhanced vascular regeneration and immunoregulation and further promoted the reconstruction of blood vessels, hair follicles, and dermal collagen matrix, eventually leading to the recovery of diabetic rat skin wounds and restoration of skin functions. This work provides a promising strategy to broaden the applicability of diverse hydrogels with a long time-consuming gelation process and to integrate different networks with various biological functions for the therapies of diabetic wounds and other complex clinical symptoms.

Bioprinting of a Blue Light-Cross-Linked Biodegradable Hydrogel Encapsulating Amniotic Mesenchymal Stem Cells for Intrauterine Adhesion Prevention

“…This is mainly because gelatin itself can promote cell adhesion and proliferation. 34 At day 7, the OD value of the GelMA/ColMA hydrogel increased significantly, indicating that the addition of ColMA can better support cell proliferation and growth, which was consistent with the results of live/dead staining. This is mainly due to the good biocompatibility of collagen and the highly porous structure of the hydrogel, which can promote cell proliferation.…”

Potential Effects of Phenolic Compounds That Can Be Found in Olive Oil on Wound Healing

“…With regard to its role in tissue regeneration and wound healing, a vanillin-enriched hydrogel was used to treat mesenchymal stem cells derived from the adipose tissue of diabetic rats and upregulated the expression of markers of vascular regeneration, collagen deposition, and hair follicle reconstruction [ 83 ]. In another study, the application of vanillin-supplemented chitosan membranes on skin incisions in diabetic rats reduced the wound size and TNF-α and IL-1β levels, increasing re-epithelialization, angiogenic stimulus, and collagen deposition [ 89 ].…”

Conductive Biomaterials as Bioactive Wound Dressing for Wound Healing and Skin Tissue Engineering

“…Conductive hydrogel has been employed as scaffold for the treatment of diabetic wounds. Jin et al recently reported a 1 3 conductive hydrogel scaffold based on AT, hyaluronic acid and gelatin [184]. Compared with nonconductive hydrogel, the conductive hydrogel was found to upregulate the level of Cx43, owing to better transport of molecules and ions between cells.…”