Injectable platelet-mimicking silk protein-peptide conjugate microspheres for hemostasis modulation and targeted treatment of internal bleeding
Yajun Shuai, Qian Yu, Meidan Zheng, Chi Yan, Jue Wang, Peng Wang, Jie Wang, Chuanbin Mao, Mingying Yang
Abstract
Uncontrolled deep bleeding, commonly encountered in surgical procedures, combat injuries, and trauma, poses a significant threat to patient survival and recovery. The development of effective hemostatic agents capable of precisely targeting trauma sites in deep tissues and rapidly halt bleeding remains a considerable challenge. Drawing inspiration from the natural hemostatic cascade, we present platelet-like microspheres composed of silk fibroin (SF) and thrombus-targeting peptides, engineered to mimic natural platelets for rapid hemostasis in vivo. These peptide/SF hemostatic microspheres, formulated using a freezing self-assembly technology, closely resemble natural platelets in terms of size, shape, and zeta potential. Moreover, they exhibit favorable cytocompatibility, hemocompatibility, and anti-cell adhesion. Assessment of fibrin polymerization revealed that these hemostatic microspheres possessed enzymatic physiological functions, similar to activated platelets, facilitating platelet adhesion, fibrin binding, and wound-triggered hemostasis. Notably, these hemostatic microspheres rapidly target the bleeding site in vivo within 5 min, with minimal dispersion elsewhere, persisting after blood clot formation. Furthermore, these microspheres exhibit favorable metabolic kinetics, with 71% degradation occurring within one-day post-subcutaneous injection. Histological assessment revealed well-preserved organ structures and minimal inflammatory responses at 14 d post-injection, supporting their long-term biocompatibility. Importantly, they can be injected and targeted into damaged blood vessels, selectively binding to fibrin and forming blood clots within 2 min, resulting in a 74% reduction in bleeding volume compared to SF microspheres alone. Therefore, these injectable SF-based hemostatic microspheres emerge as promising candidates for future rapid hemostasis in tissue injuries.