期刊
ACTA BIOMATERIALIA
卷 14, 期 -, 页码 84-95出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2014.11.035
关键词
Biomimetic material; Cardiac tissue engineering; Extracellular matrix; Fibrin; Mechanical properties
资金
- NRSA [F32 HL112538]
- Tufts University Biomedical Engineering Research Scholars (TUBERS) Program
- NIH [R00 HL093358]
- NIH-NHLBI [R21 HL115570]
- NSF [NSF1351241]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1351241] Funding Source: National Science Foundation
Solubilized cardiac extracellular matrix (ECM) is being developed as an injectable therapeutic that offers promise for promoting cardiac repair. However, the ECM alone forms a hydrogel that is very soft compared to the native myocardium. As both the stiffness and composition of the ECM are important in regulating cell behavior and can have complex synergistic effects, we sought to develop an ECM-based scaffold with tunable biochemical and mechanical properties. We used solubilized rat cardiac ECM from two developmental stages (neonatal, adult) combined with fibrin hydrogels that were cross-linked with transglutaminase. We show that ECM was retained within the gels and that the Young's modulus could be tuned to span the range of the developing and mature heart. C-kit+ cardiovascular progenitor cells from pediatric patients with congenital heart defects were seeded into the hybrid gels. Both the elastic modulus and composition of the scaffolds impacted the expression of endothelial and smooth muscle cell genes. Furthermore, we demonstrate that the hybrid gels are injectable, and thus have potential for minimally invasive therapies. ECM fibrin hybrid scaffolds offer new opportunities for exploiting the effects of both composition and mechanical properties in directing cell behavior for tissue engineering. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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