Modulating Oxidative Stress and Inflammatory Responses of Aloe vera-Silk Fibroin-Chitosan Gel Formulation in...

Chronic and diabetic wounds are characterized by persistent inflammation, excessive oxidative stress, and impaired cellular responses, collectively leading to delayed tissue repair. This study aimed to evaluate a thermoresponsive gel incorporating Aloe vera (AV) extracts and silk fibroin (SF), focusing on its biocompatibility, anti-inflammatory, antioxidant, and pro-regenerative potential. The AV: SF mixture and gel formulation were evaluated in macrophage-like THP-1 cells, and human diabetic dermal fibroblasts (HDdF) under non-induced and LPS/IL-6/TNF-α-induced inflammatory conditions. Both formulations maintained high cell viability across all cell types, indicating good biocompatibility. Under inflammatory conditions, both the AV: SF mixture and gel significantly reduced intracellular ROS levels and suppressed TNF-α and IL-1β secretion. In addition, NF-κB p65 activation was attenuated in both macrophage-like THP-1 cells and HDdF. Macrophage-like THP-1 cells displayed the M2 (CD80^low/CD206^high) phenotype, indicating modulation of macrophage polarization toward wound remodeling and repair. Overall, the AV: SF-based gel system demonstrated coordinated antioxidant, anti-inflammatory, and pro-regenerative effects in vitro. These findings support its potential as a multifunctional biomaterial for modulating inflammation-associated cellular dysfunction in chronic and diabetic wound environments.