A Bioinspired Hemostatic Nano-Sponge: Sustained Release of Honeysuckle from Mesoporous Silica for Integrated Bleeding Control and Wound Repair.

Uncontrolled hemorrhage and delayed wound healing represent critical challenges in clinical practice. To address these issues, we developed a bioinspired honeysuckle-loaded mesoporous silica nanoparticle (HS-MSN) system that integrates sustained drug release with rapid hemostasis and pro-healing functions. Inspired by the unique surface structure of waxberries, HS-MSN was synthesized via a facile adsorption method, exhibiting high surface area, hierarchical porosity, and efficient loading of bioactive honeysuckle extract. The nanocomposite demonstrated a sustained release profile lasting up to 72 h, significantly enhancing the durability and bioavailability of therapeutic components. In vitro studies showed that HS-MSN accelerated clotting initiation within 10 s in both normal and hemophilic blood models, outperforming its individual components (bare MSN or honeysuckle extract alone). The material also exhibited excellent biocompatibility, hemocompatibility, and efficient cellular uptake. Moreover, the sustained release of honeysuckle constituents potently scavenged reactive oxygen species and suppressed pyroptosis by inhibiting NLRP3 inflammasome activation and pro-inflammatory cytokine release. In multiple murine injury models (tail amputation, liver wound, and limb amputation), HS-MSN achieved rapid hemostasis, significantly reduced blood loss, and shortened clotting time. Most notably, in a hemorrhagic full-thickness wound model, HS-MSN treatment resulted in substantially accelerated wound closure, with (67.02 ± 2.56)% healing achieved within 7 days, enhanced collagen deposition, and improved re-epithelialization, significantly outperforming control groups. The combination of sustained release capability, rapid hemostasis, and potent healing promotion makes HS-MSN a promising multifunctional nanotherapeutic for managing acute hemorrhagic wounds and facilitating tissue regeneration in emergency and surgical settings.