title: Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.
abstract: Currently available skin grafts and skin substitutes for healing following third-degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative manner would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate the vulnerary efficacy and accelerated healing mechanism of a dextran-based hydrogel in a 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 re-epithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared with 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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences - Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles street, Baltimore, MD 21218, USA.
authors.forename: Yu-I
authors.initials: YI
authors.lastname: Shen
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences - Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles street, Baltimore, MD 21218, USA.
authors.forename: Hyun-Ho Greco
authors.initials: HG
authors.lastname: Song
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles street, Baltimore, MD 21218, USA.
authors.forename: Arianne
authors.initials: A
authors.lastname: Papa
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles street, Baltimore, MD 21218, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Burke
authors.affiliation: Department of Clinical Studies--Philadelphia, University of Pennsylvania School of Veterinary Medicine, 380 S. University Ave, Philadelphia, PA 19104, USA.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Volk
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences - Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles street, Baltimore, MD 21218, USA.|Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles street, Baltimore, MD 21218, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Gerecht
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D002056:Burns / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D007150:Immunohistochemistry; D011897:Random Allocation; D012038:Regeneration / Q000187:drug effects; D012680:Sensitivity and Specificity; D017592:Skin Care / Q000379:methods; D016038:Skin Transplantation / Q000379:methods; D017768:Skin, Artificial; D034421:Sus scrofa; D013552:Swine; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D020100:Hydrogels