Injectable Self-Crosslinkable Thiolated Hyaluronic Acid for Stem Cell Therapy of Atopic Dermatitis

Stem cell therapies offer great promise in regenerative medicine to reinstate the normal function of diseased tissue, thereby avoiding the need for replacement. In stem cell therapies, damaged cells are replaced or restored by regulating inflammation and the immune system. However, the low survival rate and local retention of transplanted cells pose a significant challenge. In this study, injectable self-crosslinkable hydrogels using thiol-functionalized hyaluronic acid (HA-SH) were developed to improve the efficacy of mesenchymal stem cells (MSCs) for treating atopic dermatitis (AD)-related inflammatory lesions. The gelation kinetics and mechanical properties of HA-SH hydrogels were easily tuned by varying the concentration of the polymer in the precursor solution before injection. The MSC-laden HA-SH hydrogels exhibited high cell viability (>80%) for 1 week and good in vivo biocompatibility after implantation beneath the mouse skin. Moreover, the MSC-laden HA-SH hydrogel showed increased expression of anti-inflammatory cytokines, which can alleviate the immune response. In an AD animal model, a reduction in epidermal thickness and mast cell infiltration was achieved by applying a self-crosslinkable HA-SH solution including MSCs. This HA-based injectable hydrogel represents a potential carrier of stem cells, and its strong immunomodulation capabilities can be utilized for treating inflammation-related diseases.