@article {19481, title = {Stem Cell-Containing Hyaluronic Acid-Based Spongy Hydrogels for Integrated Diabetic Wound Healing}, journal = {Journal Of Investigative Dermatology}, volume = {137}, year = {2017}, month = {2017-03-01 00:00:00}, pages = {1541-1551}, publisher = {Elsevier Inc.}, abstract = {

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
{\th}
)/M1(CD86
{\th}
) 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.

}, keywords = {diabetic foot ulcerations, spongy-like hydrogels, Stem cells}, issn = {0022-202X}, doi = {10.1016/j.jid.2017.02.976}, url = {https://doi.org/10.1016/j.jid.2017.02.976}, author = {da Silva, L. P. and Santos, T. C. and Rodrigues, D. B. and Pirraco, R. P. and Cerqueira, M. T. and Reis, R. L. and Correlo, V. M. and Marques, A. P.} }