SDF-1α loaded lipid liquid crystalline hydrogel accelerates diabetic wound healing in in vitro and in vivo models

Diabetes mellitus (DM) significantly impairs wound healing, often leading to chronic wounds with limited effective treatment options. Existing treatments often fail to provide sustained therapeutic effects, underscoring the need for advanced biomaterial-based approaches to enhance tissue regeneration. This study aimed to evaluate the wound healing efficacy of stromal cell-derived factor-1 alpha (SDF-1α)-loaded lipid liquid crystalline (LLC) hydrogel in both in vitro and in vivo models. A scratch wound healing assay was conducted on human dermal fibroblast (HDF) cells treated with allantoin (100 µg), LLC hydrogel, SDF-1α 50 ng/LLC, SDF-1α 25 ng/LLC, SDF-1α 25 ng, and a negative control. In vivo studies utilized diabetic rats (n = 10 per group) with full-thickness wounds, treated with LLC hydrogel, SDF-1α 300 ng/LLC, and polyhexamethylene biguanide (PHMB), compared to a negative control. Wound closure rates were measured on days 3, 7, 14, and 21, and histopathological analysis was performed. The SDF-1α/LLC hydrogel significantly enhanced HDF cell migration, showing a 32.8% improvement over the control (P < 0.001). Diabetic wounds treated with SDF-1α/LLC hydrogel demonstrated 51.4% faster closure by day 14 compared to the control (P < 0.001), with complete closure achieved by day 21. By day 21, SDF-1α/LLC and LLC hydrogels achieved 100% wound closure, while PHMB-treated wounds also exhibited significant healing, reaching 97.86% closure. Histological analysis revealed increased fibroblast proliferation, reduced inflammation, enhanced collagen deposition, and greater epithelial thickness, particularly in the SDF-1α/LLC group. The SDF-1α-loaded LLC hydrogel significantly enhances fibroblast migration, accelerates wound closure, and promotes tissue regeneration, making it a promising candidate for diabetic wound care.