Injectable platelet-mimicking silk protein-peptide conjugate microspheres for hemostasis modulation and targeted treatment of internal bleeding

• Published in: Journal of nanobiotechnology Vol. 23; no. 1; pp. 128 - 19
• Main Authors: Shuai, Yajun, Qian, Yu, Zheng, Meidan, Yan, Chi, Wang, Jue, Wang, Peng, Wang, Jie, Mao, Chuanbin, Yang, Mingying
• Format: Journal Article
• Language: English
• Published: London BioMed Central 20.02.2025; BioMed Central Ltd; BMC
• Subjects: Animals; Biomimetics; Biotechnology; Blood clot; Blood Platelets; Care and treatment; Chemical properties; Chemistry; Chemistry and Materials Science; Fibrin; Fibroins - chemistry; Fibroins - pharmacology; Health aspects; Hemorrhage; Hemorrhage - drug therapy; Hemostasis; Hemostasis - drug effects; Hemostatic agents; Hemostatics - chemistry; Hemostatics - pharmacology; Humans; Injectable microsphere; Male; Mice; Micro-nanoparticles; Microspheres; Molecular Medicine; Nanotechnology; Peptides; Peptides - chemistry; Peptides - pharmacology; Platelet Adhesiveness - drug effects; Polymerization; Proteins; Silk; Targeted therapy; Therapeutics, Experimental; Thrombosis; Wound closure; China; Hemostatic agents; Injectable microsphere; Micro-nanoparticles; Targeted therapy; Wound closure
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-025-03180-w

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. Graphical Abstract