Fabrication of silk fibroin microspheres via microfluidics for Co-delivery of dexamethasone and epidermal growth factor to promote skin wound healing

Background The skin, serving as the outermost barrier of the human body, is highly susceptible to injury. Wound healing is a complex biological process, and the widely used repair methodssuch as split-thickness autografts have notable drawbacks. Hence, the development of advanced biomaterials that integrate both safety and multifunctionality for skin wound repair holds significant clinical promise. Methods In this study, silk protein (SF) droplets were prepared using microfluidic technology and cross-linked with ultraviolet light to form microspheres loaded with dexamethasone (Dex) and epidermal growth factor (EGF). The fabricated microspheres were subjected to thorough material characterization. In vitro cellular experiment and in vivo animal experiment were performed to explore the anti-inflammatory properties and wound healing efficacy of the microspheres. Results Characterization via scanning electron microscopy and inverted microscopy revealed that microspheres were uniform, loosely structured, and porous, and exhibited strong liquid absorption capacity. Thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy results indicated that the material was stable and that the modification was successful. Based on the drug loading, encapsulation efficiency, and in vitro release profiles obtained during formulation optimization, 10 μg/mL EGF and 0.8 mg/mL Dex were selected for the preparation of DESF microspheres used in subsequent biological experiments (DESF microspheres, prepared by first loading EGF into SF microspheres followed by Dex post-loading). CCK-8, live/dead cell staining, and scratch assays confirmed that microspheres are non-toxic and promote cell motility. Angiogenesis experiments showed that the experimental group outperformed the control group in terms of total length, number of branching points and nodes. ELISA indicated that levels of TNF-α, IL-1β, and IL-6 were significantly reduced, suggesting that the microspheres exhibit good anti-inflammatory effects. In animal experiments, the wound healing rate in the DESF group reached 95.4% ± 3.7%. Histological and immunofluorescence analyses confirmed that DESF microspheres upregulate the expression of VEGF and CD31, downregulate TNF-α, and upregulate IL-10, thereby suppressing early-stage inflammation, promoting angiogenesis, and accelerating wound repair. Conclusion These findings suggest that the DESF microspheres can promot wound healing, with good biocompatibility, anti-inflammatory and pro-angiogenic properties. Thus, the DESF microspheres hold considerable promise for skin wound repair.