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

Author

Listed:
  • Andrea S. Carlini

    (University of California, San Diego
    Northwestern University)

  • 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)

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.

Suggested Citation

  • Andrea S. Carlini & Roberto Gaetani & Rebecca L. Braden & Colin Luo & Karen L. Christman & Nathan C. Gianneschi, 2019. "Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09587-y
    DOI: 10.1038/s41467-019-09587-y
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    Cited by:

    1. Di Wu & Jing Zhou & Yanrong Zheng & Yuyi Zheng & Qi Zhang & Zhuchen Zhou & Xiaojie Chen & Qi Chen & Yeping Ruan & Yi Wang & Zhong Chen, 2023. "Pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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