Surgical replacement or repair of diseased or defective myocardium currently involves use of either non-biological materials (e.g., Dacron, ePTFE) or material of biological origin that is rendered inert by means of chemical treatment (e.g., glutaraldehyde-fixed bovine pericardium). While these materials are useful to achieve short-term objectives such as immediate repair of septal defects or substitution of infarcted and aneurysmic myocardium, they are limited by inability to allow recruitment of host cells and thereby eventual replacement by host tissue. Cryopreserved allografts used as patch material may invoke immunogenic responses with long-term failure and systemic complications. Harvesting of host tissue such as veins or pericardium for autograft material increases invasive stress and may render suboptimal early results. We propose to investigate the use of a recently developed extracellular matrix (ECM) biological material, acellular porcine urinary bladder or intestinal submucosa, for surgical repair of infarcted myocardium. Preliminary studies suggested that myocardiogenesis and vasculogenesis occured within the material as a result, at least partially, of bone marrow-derived stem cell recruitment and differentiation. In the proposed study, that hypothesis will be tested and the healing and incorporation of this material as a myocardial prosthetic patch will be studied over time until stable resorption and replacement. Implant geometry, cardiovascular hemodynamics, cardiac performance, and cardiac electrophysiologic signal propagation both globally and locally at the patch implant site will be evaluated. The recruitment of host cells into the prosthetic material and subsequent transformation into host tissue will be analyzed by microscopic morphology, immunohistochemistry, cell labeling studies, and flow cytometry. This will aid in the determination of the source and fate of host cells recruited into the prosthetic patch, as well as the remodeling of the extracellular matrix of the material. These investigations are integral to determining the utility of acellular submucosa and elucidating mechanisms of its integration into host tissue. If this material can be used to replace infarcted myocardium with functional tissue in an animal preparation it may have therapeutic benefit greater than currently available materials or surgical procedures. Patients suffering from ischemic cardiomyopathy and associated heart failure could benefit substantially, with increased exercise capacity and reduced morbidity and mortality. Considerable savings in health care costs and improvements in patient quality of life may concomitantly be achieved.
| Cui, Jianhua; Li, Jinsheng; Mathison, Megumi et al. (2005) A clinically relevant large-animal model for evaluation of tissue-engineered cardiac surgical patch materials. Cardiovasc Revasc Med 6:113-20 |
