Optimizing the Polymer Chemistry and Synthesis Method of PolySTAT, an Injectable Hemostat
| Autor: | Robert J. Lamm, Trey J. Pichon, Nathan J. White, Suzie H. Pun, Frederick Huyan, Alexander N. Prossnitz, Xu Wang, Karl T. Manner |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Hemostatic Agent Chitosan Polymers Biomedical Engineering Chain transfer Polymer Methacrylate Combinatorial chemistry Polymerization Rats Thrombelastography Biomaterials chemistry.chemical_compound Monomer chemistry Methacrylamide Animals Reversible addition−fragmentation chain-transfer polymerization |
| Zdroj: | ACS biomaterials scienceengineering. 6(12) |
| ISSN: | 2373-9878 |
| Popis: | There is a lack of prehospital hemostatic agents, especially for noncompressible hemorrhage. We previously reported PolySTAT, a unimeric, injectable hemostatic agent, that physically cross-links fibrin to strengthen clots. In this work, we sought to improve the water-solubility and synthesis yield of PolySTAT to increase the likelihood of clinical translation, reduce cost, and facilitate future mass production. First, we focused on side-chain engineering of the carrier polymer backbone to improve water-solubility. We found that substitution of the 2-hydroxyethyl methacrylate (HEMA) monomer with glycerol monomethacrylate (GmMA) significantly improved the water-solubility of PolySTAT without compromising efficacy. Both materials increased clot firmness and decreased lysis as measured by rotational thromboelastometry (ROTEM). Additionally, we confirmed the in vivo activity of GmMA-based PolySTAT by improving rat survival in a femoral artery bleed model. Second, to reduce waste, we evaluated PolySTAT synthesis via direct polymerization of peptide monomers. Methacrylamide and methacrylate peptide-monomers were synthesized and polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. This approach markedly improved the yield of PolySTAT synthesis while maintaining its biological activity in ROTEM. This work demonstrates the flexibility of PolySTAT to a variety of comonomers and synthetic routes and establishes direct RAFT polymerization of peptide monomers as a potential route of mass production. |
| Databáze: | OpenAIRE |
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