title: Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing.
abstract: Neovascularization is a critical determinant of wound-healing outcomes for deep burn injuries. We hypothesize that dextran-based hydrogels can serve as instructive scaffolds to promote neovascularization and skin regeneration in third-degree burn wounds. Dextran hydrogels are soft and pliable, offering opportunities to improve the management of burn wound treatment. We first developed a procedure to treat burn wounds on mice with dextran hydrogels. In this procedure, we followed clinical practice of wound excision to remove full-thickness burned skin, and then covered the wound with the dextran hydrogel and a dressing layer. Our procedure allows the hydrogel to remain intact and securely in place during the entire healing period, thus offering opportunities to simplify the management of burn wound treatment. A 3-week comparative study indicated that dextran hydrogel promoted dermal regeneration with complete skin appendages. The hydrogel scaffold facilitated early inflammatory cell infiltration that led to its rapid degradation, promoting the infiltration of angiogenic cells into the healing wounds. Endothelial cells homed into the hydrogel scaffolds to enable neovascularization by day 7, resulting in an increased blood flow significantly greater than treated and untreated controls. By day 21, burn wounds treated with hydrogel developed a mature epithelial structure with hair follicles and sebaceous glands. After 5 weeks of treatment, the hydrogel scaffolds promoted new hair growth and epidermal morphology and thickness similar to normal mouse skin. Collectively, our evidence shows that customized dextran-based hydrogel alone, with no additional growth factors, cytokines, or cells, promoted remarkable neovascularization and skin regeneration and may lead to novel treatments for dermal wounds.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences-Oncology Center, and the Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Guoming
authors.initials: G
authors.lastname: Sun
authors.forename: Xianjie
authors.initials: X
authors.lastname: Zhang
authors.forename: Yu-I
authors.initials: YI
authors.lastname: Shen
authors.forename: Raul
authors.initials: R
authors.lastname: Sebastian
authors.forename: Laura E
authors.initials: LE
authors.lastname: Dickinson
authors.forename: Karen
authors.initials: K
authors.lastname: Fox-Talbot
authors.forename: Maura
authors.initials: M
authors.lastname: Reinblatt
authors.forename: Charles
authors.initials: C
authors.lastname: Steenbergen
authors.forename: John W
authors.initials: JW
authors.lastname: Harmon
authors.forename: Sharon
authors.initials: S
authors.lastname: Gerecht
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000628:therapy*; D003911:Dextrans / Q000627:therapeutic use*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012879:Skin Physiological Phenomena; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000502:physiology*
chemical_list: D003911:Dextrans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate