Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model

Abstract

Currently available skin grafts and skin substitute for healing following third-degree burn injuries is fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative fashion would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate vulnerary efficacy and accelerated healing mechanism of dextran-based hydrogel in third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved reepithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared to the dressing treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients.

Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization

“…S14) according to ANOVA analysis. Collectively these results indicate that the treatment with high-dose peptide hydrogel leads to sufficient angiogenesis to drive the rapid formation of granulation tissue without the massive vessel overgrowth early on followed by a pronounced vessel regression that is often reported with treatments that overstimulate early angiogenesis (32)(33)(34).…”

Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous Wound Healing

“…[40] It is worthy to note that our prior study demonstrated that a dextran-based (Dex-AE/PEGDA,80/20) hydrogel could promote full dermal regeneration with skin appendages on a murine third degree burn injury, [36] but the skin regeneration was incomplete during preclinical studies. [37] In this formula, polyethylene glycol (PEG) was not biodegradable and could also have potentially caused immobilization due to its hydrophilicity, which repels cell infiltration. Clearly, it is advantageous for the hydrogel to have a greater polysaccharide component.…”

“…[35][36][37] To examine its regenerative capacity, we assessed DexIEME hydrogels for two desirable applications, including treating pre-existing scars from previous wounds and acute cutaneous wounds (Figure 4). The pre-existing scars or acute wounds may take place from various impairments, including both surgical and traumatic wounds (e.g., incision, burn, and puncture).…”

“…Our prior study demonstrated that dextran-allyl isocyanate-ethylamine (Dex-AE) and polyethylene glycol-diacrylate (PEGDA) hydrogel promoted dermal regeneration on a third degree burn injury in mice, [36] but it was unable to regenerate complete skin during preclinical tests. [37] Given the pro-regenerative potential of immune modulating scaffolds for wound healing, we set forth to develop dextran-based bioabsorbable hydrogels that can modu late immune responses by promoting M2 macrophage phenotype, and further attenuating scar formation during cutaneous wound healing. Our initial screening study identified that DexIEME hydrogel has superior biocompatibility with low proinflammatory responses and favorable M2 phenotype.…”

Tissue Engineering and Regenerative Medicine in Skin Wound Healing: What Has Been Done Recently -A Mini Review

“…Another interesting study 14 suggested dextran-based hydrogels as treatment for third degree burn wound healing for rapid wound closure, re-epithelialization, enhanced extracellular matrix remodelling and even nerve reinnervation. If this could be transferred to humans, it could improve extensive burn care and improve healing reducing pain and risk of infection.…”