Treating myocardial infarction with 3D-printed conductive myocardial patch fabricated from granular composite hydrogel

Abstract

In recent years, engineered conductive myocardial patches have gained increasing attention for their potential in repairing myocardial infarction (MI). However, the traditional fabrication process of these patches often includes the use of toxic conductive monomers and crosslinking agents, along with harsh physical treatments such as low-temperature drying. These elements not only hinder the effective in situ loading of myocardial cells but also limit the efficiency and retention of cell seeding post-fabrication. To address these challenges, we developed an innovative approach using a granular composite hydrogel, comprising myocardial cell-laden microgels integrated with an interstitial conductive matrix, capable of being printed into 3D complex electroactive cardiac patches. We used microfluidic technology to encapsulate cardiomyocytes in microgels. Furthermore, we integrated the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styre ne sulfonate) into a GelMA prepolymer to fabricate a conductive matrix. This matrix was subsequently combined with microgels to form a conductive bioink, which was then utilized for printing a conductive myocardial patch. The results demonstrated that the myocardial cell-laden microgels within the patches maintained robust viability and functionality. Moreover, the patches exhibited electrical conductivity aligned with physiological levels and possessed the requisite mechanical properties for structural support to the infarcted heart. We found that these conductive cell-laden patches significantly improved left ventricular remodeling and heart function post-infarction in a rat model of MI. We believe that the design and engineering of conductive cellular myocardium patches represent a significant advancement in the treatment of MI.

Keywords

3D bioprinting / Conductive Myocardium patch / Granular composite hydrogel / Myocardial infarction repair

Funding

We acknowledge the funding support from the National Natural Science Foundation of China (No. U21A20394; No. 52305314) and the National Key Research and Development Program of China (2023YFB4605800).

Conflict of interest

The authors declare they have no competing interests.

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