Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction

Andrea S. Carlini, Roberto Gaetani, Rebecca L. Braden, Colin Luo, Karen L. Christman () and Nathan C. Gianneschi ()
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Andrea S. Carlini: University of California, San Diego
Roberto Gaetani: University of California, San Diego
Rebecca L. Braden: University of California, San Diego
Colin Luo: University of California, San Diego
Karen L. Christman: University of California, San Diego
Nathan C. Gianneschi: Northwestern University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Injectable biopolymer hydrogels have gained attention for use as scaffolds to promote cardiac function and prevent negative left ventricular (LV) remodeling post-myocardial infarction (MI). However, most hydrogels tested in preclinical studies are not candidates for minimally invasive catheter delivery due to excess material viscosity, rapid gelation times, and/or concerns regarding hemocompatibility and potential for embolism. We describe a platform technology for progelator materials formulated as sterically constrained cyclic peptides which flow freely for low resistance injection, and rapidly assemble into hydrogels when linearized by disease-associated enzymes. Their utility in vivo is demonstrated by their ability to flow through a syringe and gel at the site of MI in rat models. Additionally, synthetic functionalization enables these materials to flow through a cardiac injection catheter without clogging, without compromising hemocompatibility or cytotoxicity. These studies set the stage for the development of structurally dynamic biomaterials for therapeutic hydrogel delivery to the MI.

Date: 2019
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DOI: 10.1038/s41467-019-09587-y

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