Abstract
Pathological scars (PS) represent a common complication arising post wound healing, potentially resulting in disfigurement and impaired skin functionality in severe instances. Addressing the clinical challenge wherein conventional single treatment modalities struggle to concurrently expedite wound healing and accurately impede scar formation, this study designed and prepared a pH-responsive Bletilla striata polysaccharide (BSP) microneedle patch (BSP-As@ZIF-8 MNs) using a PDMS mold. This MNs with astragaloside Ⅳ (As) encapsulated in zeolite imidazolate framework (ZIF-8) can intelligently respond to pH variations at different stages of wound healing to enable controlled release of As. When further combined with BSP, they achieve precise synergistic therapy for wound healing and scar inhibition. Furthermore, a thorough and systematic characterization and performance assessment of the MNs were conducted, followed by an evaluation of their efficacy in enhancing wound healing and suppressing scarring using a rat model with full-thickness skin defects and a rabbit ear scar model. The experimental results showed that the BSP-As@ZIF-8 MNs exhibited favorable mechanical properties and skin penetration capabilities, alongside remarkable antibacterial efficacy and satisfactory biosafety profiles. Drug release kinetics indicated that the BSP-As@ZIF-8 MNs released 76.35% of the payload at pH 5.5 and 25.78% at pH 7.4 after 48 h, highlighting an accelerated release of As with decreasing pH levels. Further in vivo experiments demonstrated that the closure rate of BSP-As@ZIF-8 MNs reached 96.85 ± 0.9% on day 14 (p < 0.001), with nearly complete wound healing by day 21, suggesting a mechanism involving the activation of VEGF and inhibition of TNF-α, leading to expedited wound closure. Notably, BSP-As@ZIF-8 MNs prevented scar formation (minimal hypertrophic scarring observed on day 35) by reducing TGF-β1, reducing the type I/III collagen ratio, and regulating collagen deposition within the TGF-β1/Smads pathway. In conclusion, BSP-As@ZIF-8 MNs can synergistically promote wound healing and mitigating scar formation, providing a promising drug delivery strategy for wound repair and scar prevention.