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Optimizing the Polymer Chemistry and Synthesis Method of PolySTAT, an Injectable Hemostat
Robert J Lamm1, Trey J Pichon1, Frederick Huyan1
1Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, 3720 15th Avenue NE, Box 355061, Seattle, Washington 98195, United States.
ACS Biomaterials Science & Engineering
|December 15, 2020
Summary
Researchers improved PolySTAT, an injectable hemostatic agent, for better water-solubility and synthesis yield. This advancement enhances its potential for clinical use in treating severe bleeding, especially noncompressible hemorrhage.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Hemostasis Research
Background:
- A critical need exists for effective prehospital hemostatic agents, particularly for noncompressible hemorrhage.
- PolySTAT, an injectable agent, was previously developed to strengthen blood clots by physically cross-linking fibrin.
- Current limitations include challenges in water-solubility and synthesis efficiency, hindering clinical translation and large-scale production.
Purpose of the Study:
- To enhance the water-solubility and synthesis yield of PolySTAT for improved clinical applicability and cost-effectiveness.
- To explore side-chain engineering of the polymer backbone to boost water-solubility.
- To investigate direct polymerization methods for more efficient PolySTAT synthesis.
Main Methods:
- Side-chain engineering: Replacing 2-hydroxyethyl methacrylate (HEMA) with glycerol monomethacrylate (GmMA) in the PolySTAT backbone.
- Efficacy assessment: Evaluating clot firmness and lysis using rotational thromboelastometry (ROTEM).
- In vivo validation: Testing GmMA-PolySTAT in a rat femoral artery bleed model.
- Synthesis optimization: Employing reversible addition-fragmentation chain transfer (RAFT) polymerization for direct synthesis of peptide monomers.
Main Results:
- Glycerol monomethacrylate (GmMA)-based PolySTAT demonstrated significantly improved water-solubility without compromising hemostatic efficacy.
- Both HEMA- and GmMA-based PolySTAT formulations increased clot firmness and reduced lysis in ROTEM assays.
- GmMA-PolySTAT significantly improved survival rates in a rat femoral artery hemorrhage model.
- Direct RAFT polymerization of peptide monomers markedly increased PolySTAT synthesis yield while preserving biological activity.
Conclusions:
- PolySTAT exhibits flexibility in its chemical structure and synthetic pathways, allowing for optimization.
- Glycerol monomethacrylate (GmMA) is a viable comonomer for enhancing PolySTAT's water-solubility and maintaining efficacy.
- Direct RAFT polymerization of peptide monomers presents a promising route for the cost-effective, large-scale production of PolySTAT.
- These advancements bring PolySTAT closer to clinical application for managing severe bleeding.
