Injectable Self-Oxygenating Cardio-Protective and Tissue Adhesive Silk-Based Hydrogel for Alleviating Ischemia After Mi Injury

Shabir Hassan, Zahra Rezaei, Eder Luna, Dilara Yilmaz-Aykut, Myung Chul Lee, Ana Marie Perea, Anurag Jamaiyar, Nicole Bassous, Minoru Hirano, Fatima Mumtaza Tourk, Cholong Choi, Malin Becker, Iman Yazdi, Kai Fan, Alan Eduardo Avila-Ramirez, David Ge, Reza Abdi, Sudeshna Fisch, Jeroen Leijten, Mark W. FeinbergBiman B. Mandal, Ronglih Liao, Su Ryon Shin*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.

Original languageEnglish
JournalSmall
DOIs
Publication statusAccepted/In press - 2024

Keywords

  • UT-Hybrid-D
  • Oxygenating microparticles
  • Silk hydrogel
  • Stromal differentiation factor
  • Vascularization
  • Myocardial infarction

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