Thiolated gellan gum/polyethylene glycol diacrylate hydrogel containing secretome as a wound dressing: In vitro and in vivo studies

Wound healing and dermal reconstitution are complex processes that rely on the interplay of various cellular and molecular factors. The treatment of chronic wounds represents an area of concern in most clinical management, as it is mostly associated with delayed healing and rising costs. This study was designed to investigate the efficacy of a novel bioactive hydrogel by integrating a stem cell-derived secretome into a dual-network matrix of thiolated gellan gum (TGG) and polyethylene glycol diacrylate (PEGDA). Hence, TGG with a free thiol amount of 95.5 µmol g −1 , PEGDA, and secretome derived from stem cells were incorporated in the hydrogel structure. The thiol-ene crosslinked structure was designed to provide mechanical support while enabling the incorporation of secretome components. The physico/chemical properties of the synthesized hydrogels, including swelling ratio, SEM, FT-IR, rheological behavior, texture analysis, porosity determination, in vitro and in vivo tests, were evaluated. For the in vivo test, 1 cm full-thickness wounds were created on the rats, and the gels were applied with/without secretome to study the wound contraction and re-epithelialization period. The results showed that the optimized hydrogel had a highly porous structure with the pore size ranging from about 1.24 μ m to less than 294 μ m. Rheological analysis revealed that the storage (G') and loss (G'') modules both increased with higher PEGDA content, indicating the formation of a more elastic hydrogel network. Besides, the evaluation of secretome-loaded hydrogels demonstrated that hydrogels are biocompatible with human umbilical vein endothelial cells (HUVECs) (cell viability >95%). The in vivo test confirmed that the provided hydrogel containing secretome offers a desirable therapeutic strategy for chronic wound healing (up to day 9). These findings establish the developed hydrogel as a highly promising and multifunctional dressing for wound healing.