In Vitro Assessment of Chitosan‐PEG Hydrogels Enriched with MSCs‐Exosomes for Enhancing Wound Healing

Abstract Regenerating skin tissue remains a major challenge in medical science, especially due to the risk of scarring and prolonged healing, which becomes even more complicated in people with diabetes. Recent advancements have led to the creation of therapeutic dressings incorporating drug‐delivery systems to tackle these issues. Exosomes (Exos) derived from mesenchymal stem cells (MSCs) have gained significant attention for mediating therapy without directly using cells, thanks to their natural anti‐inflammatory and tissue repair properties mirroring those of MSCs. In this study, an advanced wound dressing combines chitosan (CS) and polyethylene glycol (PEG) hydrogel with adipose MSCs‐derived Exos (ADMSCs‐Exos). This composite, formed using a straightforward blending technique, is engineered to improve the healing process of severe skin injuries by steadily releasing Exos as the hydrogel degrades. The in vitro studies demonstrate that this hydrogel‐exosome dressing greatly enhances endothelial cell migration, reduces oxidative stress, and promotes angiogenesis, crucial for effective wound healing. Additionally, real time‐polymerase chain reaction (RT‐PCR) analysis revealed significant upregulation of key genes involved in these processes, supporting the therapeutic potential of the hydrogel‐Exo combination. These findings emphasize the potential of this hydrogel‐Exos combination as an innovative and promising solution for advanced wound care.