Current cell-based therapies administered after myocardial infarction (MI) show limited efficacy due to subpar cell retention in a dynamically beating heart. In particular, cardiac patches generally provide a cursory level of cell attachment due to the lack of an adequate microenvironment. From this perspective, decellularized cell-derived ECM (CDM) is attractive in its recapitulation of a natural biophysical environment for cells. Unfortunately, its weak physical property renders it difficult to retain in its original form, limiting its full potential. Here, a novel strategy to peel CDM off from its underlying substrate is proposed. By physically stamping it onto a polyvinyl alcohol hydrogel, the resulting stretchable extracellular matrix (ECM) membrane preserves the natural microenvironment of CDM, thereby conferring a biological interface to a viscoelastic membrane. Its various mechanical and biological properties are characterized and its capacity to improve cardiomyocyte functionality is demonstrated. Finally, evidence of enhanced stem cell delivery using the stretchable ECM membrane is presented, which leads to improved cardiac remodeling in a rat MI model. A new class of material based on natural CDM is envisioned for the enhanced delivery of cells and growth factors that have a known affinity with ECM.
Bibliographical noteFunding Information:
I.G.K. and M.P.H. contributed equally to this work. This work was supported by a National Research Foundation of Korea (NRF) grant (No. 2015R1A2A2A04004469) from the Ministry of Science, ICT and Future Planning, Republic of Korea. This work was also supported by the Technology Innovation Program (or Industrial Strategic Technology Development Program) (10063334, Vascularized 3D tissue (liver/heart, cancer) chip for evaluation of drug efficacy and toxicity) funded by the Ministry of Trade, industry & Energy (MI, Korea).
All Science Journal Classification (ASJC) codes
- Biomedical Engineering
- Pharmaceutical Science