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by claude@2026-07, 2026-07-04
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The paper studies a recombinant, enzyme-responsive elastin-like polypeptide hemostat designed to stabilize fibrin clots and restore coagulation in thrombocytopenia, using a peptide library (Q-block-ELPs) that self-assembles and phase separates at body temperature. The key finding is that Q-block-ELPs increase fibrin network density and stiffness in vitro, and in a thrombocytopenic mouse model they reduce blood loss and accelerate clot formation by incorporating glutamine motifs recognized by coagulation factor XIIIa for site-specific grafting into fibrin during clot formation. A stated limitation is that the work focuses on preclinical in vitro and animal outcomes, with patent-related commercialization constraints noted via inventor disclosures. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Hemorrhage remains a leading cause of mortality in trauma and surgery, and treatment options are limited for thrombocytopenic patients with impaired platelet function. Current plasma-derived hemostatic products face challenges including limited supply, storage requirements, and infectious risk. Here we report a recombinant protein-based hemostat designed to enhance clot mechanics through enzyme responsiveness and self-assembly, which integrates biophysical design principles with clot-targeted drug delivery. We rationally designed a library of enzyme-responsive glutamine (Q)-containing block elastin-like polypeptides (Q-block-ELPs) that reinforce fibrin clots through phase separation and covalent cross-linking. Q-block-ELPs incorporate glutamine residues within a peptide motif recognized by coagulation factor XIIIa, enabling site-specific grafting into fibrin networks during clot formation. By tuning polymer length, Q-block valency, and lower critical solution temperature (LCST) behavior, we engineered Q-block-ELPs to phase separate at body temperature and integrate into the fibrin architecture. In vitro, Q-block-ELPs increase fibrin network density and stiffness. In a thrombocytopenic mouse model, systemic administration reduced blood loss and accelerated clot formation. This strategy delivers a programmable, pathogen-free platform for systemic bleeding control, bridging biophysical protein design with translational hemostatic therapy, addressing an urgent need for platelet-deficient bleeding disorders.
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Abstract
Hemorrhage remains a leading cause of mortality in trauma and surgery, and treatment options are limited for thrombocytopenic patients with impaired platelet function. Current plasma-derived hemostatic products face challenges including limited supply, storage requirements, and infectious risk. Here we report a recombinant protein-based hemostat designed to enhance clot mechanics through enzyme responsiveness and self-assembly, which integrates biophysical design principles with clot-targeted drug delivery. We rationally designed a library of enzyme-responsive glutamine (Q)-containing block elastin-like polypeptides (Q-block-ELPs) that reinforce fibrin clots through phase separation and covalent cross-linking. Q-block-ELPs incorporate glutamine residues within a peptide motif recognized by coagulation factor XIIIa, enabling site-specific grafting into fibrin networks during clot formation. By tuning polymer length, Q-block valency, and lower critical solution temperature (LCST) behavior, we engineered Q-block-ELPs to phase separate at body temperature and integrate into the fibrin architecture. In vitro, Q-block-ELPs increase fibrin network density and stiffness. In a thrombocytopenic mouse model, systemic administration reduced blood loss and accelerated clot formation. This strategy delivers a programmable, pathogen-free platform for systemic bleeding control, bridging biophysical protein design with translational hemostatic therapy, addressing an urgent need for platelet-deficient bleeding disorders.
Competing Interest Statement
Michael Nash and Ivan Urosev are inventors on a patent application related to the Q-block-ELP technology described in this manuscript. All other authors declare no competing interests.
Footnotes
We have improved the SDS-PAGE gels in the main text, added mass spectrometry analysis to the supplementary information (Figure S1), and added additional animal experimental data (Figure S8).
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