The long-term objective of this project is to develop a tissue engineered cardiac graft (TECG) for use in the surgical repair of congenital and acquired lesions of the heart. The end-point objective of the research proposed herein is to develop a structurally well-organized and electromechanically functional TECG eliciting demonstrable mechanical benefits in an in vivo rat model of myocardial infarction (Ml). This end-point objective will be approached by first quantifying the efficacy of protein-modified, poly(glycerol sebacate) (PGS) elastomeric scaffolds exhibiting cell-orienting 3-D open pore structures (cellular guidance motifs; CGM) to promote cardiomyocyte (CM) adhesion, survival, and alignment. Secondly, the efficacy of in vitro biaxial mechanical stimulation in promoting the organization of electromechanically functional TECG suitable for implantation will be assessed.
The specific aims are: 1. Microfabricate elastomeric scaffolds with cellular guidance motifs (CGM). 2. Quantify CM adhesion, survival, and alignment on protein-modified CGM-PGS scaffolds. 3. Quantify TECG electromechanical function in response to in vitro biaxial stretch. 4. In vivo studies of TECG in a rodent model of myocardial infarction (Ml). ? ? ?
|Cheng, Mingyu; Moretti, Matteo; Engelmayr, George C et al. (2009) Insulin-like growth factor-I and slow, bi-directional perfusion enhance the formation of tissue-engineered cardiac grafts. Tissue Eng Part A 15:645-53|
|Freed, Lisa E; Engelmayr Jr, George C; Borenstein, Jeffrey T et al. (2009) Advanced material strategies for tissue engineering scaffolds. Adv Mater 21:3410-8|
|Mobine, Hector R; Engelmayr Jr, George C; Moussazadeh, Nelson et al. (2009) Encapsulated pheochromocytoma cells secrete potent noncatecholamine factors. Tissue Eng Part A 15:1719-28|
|Nichol, Jason W; Engelmayr Jr, George C; Cheng, Mingyu et al. (2008) Co-culture induces alignment in engineered cardiac constructs via MMP-2 expression. Biochem Biophys Res Commun 373:360-5|
|Engelmayr Jr, George C; Cheng, Mingyu; Bettinger, Christopher J et al. (2008) Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nat Mater 7:1003-10|