Infusible Extracellular Matrix Biomaterial Enhances Cell‐Specific Pro‐Repair Responses Following Acute Myocardial Infarction
To mitigate the pathological effects of myocardial infarction, we developed and investigated a pro-reparative decellularized extracellular matrix (ECM) biomaterial, an intravascularly infusible ECM (iECM). However, the cellular and molecular mechanisms by which iECM mediates repair are unknown because investigations have relied on bulk techniques. Here, we leverage single-nucleus RNA sequencing (snRNAseq) to measure pro-repair responses in various cell types across acute timepoints (1, 3, and 7 days post infusion). In iECM, we found pro-reparative macrophage activation, fibroblast remodeling, increased vascular development, lymphangiogenesis, cardioprotection, and neurogenesis. These findings are validated through spatial transcriptomics. Thus, we define the pro-reparative nature of the decellularized ECM biomaterial on cardiac cell types and elucidate previously undiscovered therapeutic pathways, further demonstrating the potential of iECM as an MI therapy, as well as display the wealth of data generated from next-generation sequencing.
Authors
- Karen L. Christman (ORCID: https://orcid.org/0000-0002-6179-898X)
- Zhenxing Fu (ORCID: https://orcid.org/0000-0002-5674-2105)
- Emily Gardner (ORCID: https://orcid.org/0000-0002-1265-2298)
- Michael Nguyen (ORCID: https://orcid.org/0000-0003-1847-4557)
- Maria Karkanitsa (ORCID: https://orcid.org/0000-0003-3474-2371)
- Kevin R. King (ORCID: https://orcid.org/0000-0003-1472-2189)
- Justin Yu (ORCID: https://orcid.org/0000-0001-5917-5401)
- Julian Cheng
- Joshua M. Mesfin (ORCID: https://orcid.org/0000-0003-1022-8175)
- Van K. Ninh (ORCID: https://orcid.org/0000-0001-6017-4035)
- Colin Luo (ORCID: https://orcid.org/0000-0002-3269-2027)
- Alexander Chen (ORCID: https://orcid.org/0000-0002-8396-8759)
- Shuanglin Cao (ORCID: https://orcid.org/0000-0002-5599-9267)
- Kate E. Reimold (ORCID: https://orcid.org/0009-0006-5353-4614)
- Elizabeth Wong
- Sriya N. Paleti
- Quincy P. Lyons (ORCID: https://orcid.org/0009-0003-1042-5627)
- Benjamin D. Bridgelal (ORCID: https://orcid.org/0009-0007-8986-5201)
- Connor Uhre
Institutions
- University of California San Diego (US)
- Sanford Consortium for Regenerative Medicine (US)
- La Jolla Bioengineering Institute (US)
Publication Details
- Journal
- Advanced Healthcare Materials
- Published
- 2025-12-18
- DOI
- https://doi.org/10.1002/adhm.202503469
- Primary Topic
- Tissue Engineering and Regenerative Medicine
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- American Heart Association
- National Institutes of Health
- University of California, San Diego
- National Heart, Lung, and Blood Institute
- National Institute of Biomedical Imaging and Bioengineering
- School of Medicine, University of California, San Diego