rada16-i and Hemorrhage

Ionic self-assembly of the peptide RADARADARADARADA (RADA16-1) may form a well-defined nanofiber and eventually a hydrogel scaffold, with a water content of over 99.5%. This leads to the establishment of a nanofiber barrier that can be used to achieve complete hemostasis in less than 20 s in multiple tissues and in a variety of different wounds. In the present study, the nanofiber scaffolds of RADA16-1 peptide were sonicated into smaller fragments to identify possible molecular mechanisms underlying the rapid cessation of bleeding associated with these materials. Atomic force microscopy (AFM), circular dichroism (CD), and rheometry were also used to evaluate the re-assembly kinetics of this peptide. A bleeding control experiment was performed in animal models to uncover the molecular mechanisms underlying this fast hemostasis. In this way, these sonicated fragments not only quickly reassembled into nanofibers indistinguishable from the original material, but the degree of reassembly was also correlated with an increase in the rigidity of the scaffold and increased as the time required for hemostasis increased.

Topics: Animals; Coagulants; Disease Models, Animal; Hemorrhage; Microscopy, Atomic Force; Models, Molecular; Nanofibers; Peptides; Protein Structure, Secondary; Rats

We evaluated the hemostatic efficacy of a biological self-assembling peptide RADA16-I in a rat kidney injury model. Adult male rats were randomized into five groups: sham operation (no renal excision), no hemostatic agent (control), commercially available gelatin sponge (Gelfoam), 1% RADA16-I, and 2% RADA16-I. After left partial nephrectomy, the anesthetized animal was anticoagulated using 300 IU x kg(-1) heparin, and the topical hemostatic agent was applied to the injury. Blood loss and mean arterial pressure (MAP) were recorded. As was the case for Gelfoam, 2% RADA16-I produced marked hemostasis versus controls (p < 0.01). Blood loss with 1% and 2% RADA16-I was significantly less than controls. The decline in MAP during surgery was less with 2% versus 1% RADA16-I. RADA16-I also resulted in less histological tissue responses than Gelfoam. These data suggest that RADA16-I can stop hemorrhage, with only minimal tissue responses, in experimental renal injury.

Topics: Analysis of Variance; Animals; Blood Pressure; Dose-Response Relationship, Drug; Hemorrhage; Hemostatics; Kidney; Male; Microscopy, Atomic Force; Nanofibers; Nephrectomy; Peptides; Postoperative Hemorrhage; Rats