Modified-Hyaluronic Acid Based Hydrogels for Mesenchymal Stem Cell Delivery of the Wound: Optimization, Characterization, and In-Vivo Experiment

Following the injury, skin which is the largest physical barrier against harmful external stimuli, enters the four-stage healing process, including Hemostasis, inflammation, proliferation, and maturation. Hyaluronic acid (HA), as one of the main components of the skin extracellular matrix, has granted promising results in skin tissue engineering applications. Herein, by the use of design expert software, different experiment conditions were investigated to optimize the hydrogel formulation features such as modification degree, photo-crosslinker concentration, UV exposure time, and polymer concentration as a sign of morphological appearance, swelling degree, mechanical properties, and degradation time. Then, Wharton's jelly-derived mesenchymal stem cell (WJ-MSC), with potential activity for skin regeneration, was cultured on the final selected modified-HA hydrogel, and proliferation of the MSCs was investigated. The in-vivo data showed enhanced tissue regeneration and scarless wound healing within ۲۱ days in the studied rats. In addition, pathological and molecular studies of animal tissue revealed that the final hydrogel composite enhanced scarless wound healing due to the greater expression of VEGF, IL-۱۰, TGF-B۳/ TGF-B۱ ratio, and Collagen III/ Collagen I ratio. As a consequence, the in-vitro and in-vivo evaluations proposed that this composite hydrogel can be a good choice for scarless healing of acute wounds.