John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Division of Trauma, Emergency Surgery, and Surgical Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA.
Sci Adv. 2020 Jul 31;6(31):eaba0588. doi: 10.1126/sciadv.aba0588. eCollection 2020 Jul.
Uncontrolled noncompressible hemorrhage is a major cause of mortality following traumatic injuries in civilian and military populations. An injectable hemostat for point-of-care treatment of noncompressible hemorrhage represents an urgent medical need. Here, we describe an injectable hemostatic agent via polymer peptide interfusion (HAPPI), a hyaluronic acid conjugate with a collagen-binding peptide and a von Willebrand factor-binding peptide. HAPPI exhibited selective binding to activated platelets and promoted their accumulation at the wound site in vitro. In vivo studies in mouse tail vein laceration model demonstrated a reduction of >97% in both bleeding time and blood loss. A 284% improvement in the survival time was observed in the rat inferior vena cava traumatic model. Lyophilized HAPPI could be stably stored at room temperature for several months and reconstituted during therapeutic intervention. HAPPI provides a potentially clinically translatable intravenous hemostat.
未控制的非压迫性出血是民用和军用创伤后死亡的主要原因。一种用于非压迫性出血即时治疗的可注射止血剂是一种迫切的医疗需求。在这里,我们描述了一种通过聚合物肽融合(HAPPI)的可注射止血剂,它是一种透明质酸缀合物,带有胶原蛋白结合肽和血管性血友病因子结合肽。HAPPI 表现出对活化血小板的选择性结合,并促进其在体外伤口部位的聚集。在小鼠尾静脉切割模型的体内研究中,出血时间和失血量减少了 >97%。在大鼠下腔静脉创伤模型中,观察到生存时间提高了 284%。冻干的 HAPPI 可以在室温下稳定储存数月,并在治疗干预期间重新配制。HAPPI 提供了一种潜在的可临床转化的静脉内止血剂。