Tissue engineering aims at building 3-dimensional living substitutes that are equal to or better than the damaged tissue to be replaced. The development of such a tissue replacement requires a multidisciplinary approach and careful attention to the optimal cell source, the interactions of growth factors and extracellular milieu, and the scaffolding design. This article is a review of the tissue engineering programs of the National Heart, Lung, and Blood Institute, which support research efforts to translate novel approaches for the treatment of cardiovascular disease. Recent progress is discussed, which highlights some major questions relevant to cardiovascular tissue engineering. The National Heart, Lung, and Blood Institute has a strong interest in tissue engineering and will continue to foster the practical, clinical, and commercial development of research discoveries in this emerging field.
"Treatment of arterial obstructions by autologous vascular grafting has several technical and patient-related risks . In contrast to synthetic substitutes that faced complications with compatibility and biological function, cell-seeded tissue engineered vessels (TEVs) have been shown to perform better at the blood-material interface . "
[Show abstract][Hide abstract] ABSTRACT: A quantitative understanding of the complex interactions between cells, soluble factors, and the biological and mechanical properties of biomaterials is required to guide cell remodeling toward regeneration of healthy tissue rather than fibrocontractive tissue. In the present study, we characterized the combined effects of boundary stiffness and transforming growth factor-β1 (TGF-β1) on cell-generated forces and collagen accumulation. We first generated a quantitative map of cell-generated tension in response to these factors by culturing valvular interstitial cells (VICs) within micro-scale fibrin gels between compliant posts (0.15-1.05 nN/nm) in chemically-defined media with TGF-β1 (0-5 ng/mL). The VICs generated 100-3000 nN/cell after one week of culture, and multiple regression modeling demonstrated, for the first time, quantitative interaction (synergy) between these factors in a three-dimensional culture system. We then isolated passive and active components of tension within the micro-tissues and found that cells cultured with high levels of stiffness and TGF-β1 expressed myofibroblast markers and generated substantial residual tension in the matrix yet, surprisingly, were not able to generate additional tension in response to membrane depolarization signifying a state of continual maximal contraction. In contrast, negligible residual tension was stored in the low stiffness and TGF-β1 groups indicating a lower potential for shrinkage upon release. We then studied if ECM could be generated under the low tension environment and found that TGF-β1, but not EGF, increased de novo collagen accumulation in both low and high tension environments roughly equally. Combined, these findings suggest that isometric cell force, passive retraction, and collagen production can be tuned by independently altering boundary stiffness and TGF-β1 concentration. The ability to stimulate matrix production without inducing high active tension will aid in the development of robust tissue engineered heart valves and other connective tissue replacements where minimizing tissue shrinkage upon implantation is critical.
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular disease represents one of the major health challenges in modern times and is the number one cause of death globally. Thus, numerous studies are under way to identify effective cell- and/or growth factor-based therapies for repairing damaged cardiac tissue. In this regard, improving the engraftment or survival of regenerative cells and prolonging growth factor exposure have become fundamental goals in advancing these therapeutic approaches. Therefore, biomaterials have emerged as innovative scaffolds for the delivery of both cells and proteins in tissue engineering applications. In the present study, electrospinning was used to generate smooth homogenous polymeric fibers, which consisted of a PLGA/NCO-sP(EO-stat-PO) polymer blend encapsulating the cardioactive growth factor, Neuregulin-1 (Nrg). We evaluated the biocompatibility and degradation of this Nrg-containing biomaterial in a rat model of myocardial ischemia. Following implantation, histological analysis revealed the presence of an initial acute inflammatory response, which was followed by a chronic inflammatory phase, characterized by the presence of giant cells. Notably, the scaffold remained in the heart after 3 months. Furthermore, increase in the M2:M1 macrophage ratio following implantation suggested the induction of constructive tissue remodeling. Taken together, the combination of Nrg-encapsulating scaffolds with cells capable of inducing cardiac regeneration could represent an ambitious and promising therapeutic strategy for repairing diseased or damaged myocardial tissue.
Tissue Engineering Part A 02/2015; DOI:10.1089/ten.TEA.2014.0523 · 4.64 Impact Factor
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