DGGcm Loaded with LGG for Promoting Diabetic Infected Wound Healing

ABSTRACT The skin serves as the body's primary defense barrier, crucial for protection against external aggressors and maintaining stable body temperature. Diabetic patients, due to vascular and neuropathic damage induced by hyperglycemia, experience significantly impaired healing capacity, rendering them vulnerable to chronic wounds and infections, which may necessitate amputations. Therefore, investigating effective treatments that expedite wound healing in diabetic patients is of considerable clinical importance. This study evaluates the efficacy of Dextran‐Gelatin‐Gellan Gum composite microspheres (DGGcm) loaded with Lactobacillus rhamnosus (LGG) in the repair of full‐thickness skin defects and infected wounds in diabetic rats. Uniformly shaped DGGcm were prepared using a combination of emulsification and microfluidic technology. After LGG loading, in vitro experiments—including cell live/dead staining, CCK‐8 proliferation assays, migration and tubule formation evaluations, and antibacterial testing—were performed to assess the effects of DGGcm combined with LGG on cell proliferation, migration, angiogenesis, and antibacterial efficacy. Subsequently, a diabetic rat model with full‐thickness skin defects and infections was established to compare the therapeutic effects of DGGcm combined with LGG against other treatment groups. Histological analysis, qRT‐PCR, and Western Blot (WB) assays were utilized to evaluate tissue repair, collagen deposition, and cytokine expression. The study demonstrated that DGGcm possesses excellent biocompatibility and degradability, with LGG incorporation facilitating sustained release. In vitro experiments revealed that DGGcm combined with LGG significantly enhanced cell proliferation, migration, tubule formation, and antibacterial properties. In vivo results indicated that this combination markedly accelerated wound healing in diabetic rats. Histological analysis revealed that the DGGcm‐LGG formulation closely resembled normal skin architecture, exhibiting effective tissue restoration, fiber alignment, and collagen deposition. Molecular biology analyses indicated that DGGcm combined with LGG significantly suppressed the expression of the pro‐inflammatory cytokine IL‐6, elevated the expression of the anti‐inflammatory cytokine IL‐10, and promoted the expression of critical wound healing proteins, including CD31, KI‐67, MMP‐2, TGF‐β, VEGF, and α‐SMA. This study successfully developed DGGcm with exceptional biocompatibility and degradability, effectively loading LGG to achieve sustained release. The DGGcm‐LGG combination significantly enhances cell proliferation, migration, tubule formation, and antibacterial efficacy, thereby promoting the healing of infected wounds in diabetic rats. These findings propose a novel therapeutic strategy with substantial clinical application potential for wound repair in diabetic patients.