Author(s): Silva, Lucília Pereira ; Santos, T. C. ; Rodrigues, Daniel Barreira ; Pirraco, Rogério P. ; Cerqueira, Mariana Teixeira ; Reis, R. L. ; Correlo, V. M. ; Marques, A. P.
Date: 2017
Persistent ID: https://hdl.handle.net/1822/52067
Origin: RepositóriUM - Universidade do Minho
Subject(s): Diabetic foot ulcerations; Spongy-like hydrogels; Stem cells
The detailed pathophysiology of diabetic foot ulcers is yet to be established and improved treatments are still required. We propose a strategy that directs inflammation, neovascularization, and neoinnervation of diabetic wounds. Aiming to potentiate a relevant secretome for nerve regeneration, stem cells were precultured in hyaluronic acid-based spongy hydrogels under neurogenic/standard media before transplantation into diabetic mice full-thickness wounds. Acellular spongy hydrogels and empty wounds were used as controls. Reepithelialization was attained 4 weeks after transplantation independently of the test groups, whereas a thicker and more differentiated epidermis was observed for the cellular spongy hydrogels. A switch from the inflammatory to the proliferative phase of wound healing was revealed for all the experimental groups 2 weeks after injury, but a significantly higher M2(CD163 þ )/M1(CD86 þ ) subtype ratio was observed in the neurogenic preconditioned group that also failed to promote neoinnervation. A higher number of intraepidermal nerve fibers were observed for the unconditioned group probably due to a more controlled transition from the inflammatory to the proliferative phase. Overall, stem cell-containing spongy hydrogels represent a promising approach to enhance diabetic wound healing by positively impacting re-epithelialization and by modulating the inflammatory response to promote a successful neoinnervation.
