Journal
BIOMATERIALS
Volume 34, Issue 2, Pages 393-401Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.09.038
Keywords
Cardiac tissue engineering; Elastomer; Bioreactor; Cardiac ischemia; Angiogenesis; VEGF
Funding
- NIH [HL088913, HL076485, EB002520]
- Swiss National Science Foundation [310030-127426]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R21HL108668, R21HL089913, R01HL076485] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [P41EB002520] Funding Source: NIH RePORTER
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Key requirements for cardiac tissue engineering include the maintenance of cell viability and function and the establishment of a perfusable vascular network in millimeters thick and compact cardiac constructs upon implantation. We investigated if these requirements can be met by providing an intrinsic vascularization stimulus (via sustained action of VEGF secreted at a controlled rate by transduced myoblasts) to a cardiac patch engineered under conditions of effective oxygen supply (via medium flow through channeled elastomeric scaffolds seeded with neonatal cardiomyocytes). We demonstrate that this combined approach resulted in increased viability, vascularization and functionality of the cardiac patch. After implantation in a mouse model of myocardial infarction, VEGF-expressing patches displayed significantly improved engraftment, survival and differentiation of cardiomyocytes, leading to greatly enhanced contractility as compared to controls not expressing VEGF. Controlled VEGF expression also mediated the formation of mature vascular networks, both within the engineered patches and in the underlying ischemic myocardium. We propose that this combined cell-biomaterial approach can be a promising strategy to engineer cardiac patches with intrinsic and extrinsic vascularization potential. (C) 2012 Elsevier Ltd. All rights reserved.
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