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

Abstract

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 selfcrosslinkable 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.

Immunomodulatory Hydrogels: Advanced Regenerative Tools for Diabetic Foot Ulcer

“…[ 81 ] With the subcutaneous injection of thiol‐functionalized hyaluronic acid hydrogels carrying adipose MSCs, repressed expression of IL‐13, chemokine ligand 11 (CCL11), and CCL24, the weakening of epidermal thickness and mast cell permeation are seen in the target region, accompanied by the amelioration of atopic dermatitis ( Figure A,B). [ 82 ] Induced pluripotent stem cells released from the biocompatible hydrogel reduced the infiltration of neutrophils and CD4+ and CD8+ T cells in the myocardium to trigger cardiovascular repair postmyocardial infarction (Figure 6C). [ 83 ] Through transfecting with lentiviral vector loading IL‐4 gene, the genetically modified MSCs display strengthened immunosuppressive abilities, characterized by a markedly increase of IL‐4 expression and macrophage polarizing to M2 phenotype, thereby favoring inflammation ablation and bone defect healing.…”

“…[ 42 ] Additionally, MSCs‐encapsulated hydrogels might be another feasible option, given that this kind of hybrid mitigates aberrant immune microenvironment to abolish skin inflammation responsible for the pathophysiological progression of DFU and promote angiogenesis and tissue regeneration. [ 82 ]…”

“…Reproduced with permission. [ 82 ] Copyright 2022, American Chemical Society. C) Injection of induced pluripotent stem cells encapsulated in hydrogels reduces the infiltration of CD4+ T cells and CD8+ T cells in the injured site of myocardial infarction.…”

Cellular modifications and biomaterial design to improve mesenchymal stem cell transplantation

“…These hydrogels can take the form of a bulk material with suspended MSCs or MSC aggregates, microcarriers with MSCs seeded on the surface, microcapsules with encapsulated MSCs, or as a combination of these forms. Bulk hydrogels are the simplest injectable materials in terms of material preparation, cell encapsulation, and administration, 173 but may possess limited nutrient and oxygen diffusion relative to hydrogel density and dimensions. 174 Encapsulation of MSCs within a bulk hydrogel poses an upper limit for the dimension and size of the injected biomaterial.…”

Electrospun fibers as carriers for topical drug delivery and release in skin bandages and patches for atopic dermatitis treatment

“…The treatment costs reported exceeded those related to cardiovascular issues or diabetes, which are usually considered examples of the most expensive health problems (Flohr & Hay, 2021; Lim et al, 2017). Therefore, medical doctors and scientists are constantly looking for new treatment possibilities to improve the efficiency of the existing ones and reduce costs (Lee et al, 2022). AD is one of the most common skin diseases.…”