Bioengineered Muscle Implants
Abstract Fundamental research has defined many of the mechanistic events that mediate congenital malformations and the pathological disease processes that alter cardiac structure and function. Despite these efforts, there are a limited number of clinical treatment options available for many of these conditions. In many cases, even for disease processes that cause focal defects in the ventricular wall, the only viable treatment is the complete replacement of the damaged organ by transplant. Unfortunately, the supply of cardiac tissue that is available for transplant therapy remains chronically, and critically, short of demand. The reconstruction of a specific domain of dysfunctional ventricular tissue with a cell-based therapy is a potential avenue of treatment. One of the most direct strategies in this type of treatment regime is the injection of a suspension of fetal or neonatal cardiac myocytes into the injured domain. In small animal models, two limitations have become apparent with this strategy. First, differentiated myocytes do not undergo migration when they are injected into scar tissue and as a result they tend to remain concentrated in the vicinity of the injection site. Second, the myocytes that survive in the injection site are not well integrated into the healthy tissue and contract at rates that are independent of the surrounding myocardium. The long-term objective of this project is to circumvent the limitations of injection therapy by fabricating a cardiac muscle prosthesis that mimics the three dimensional architecture of the intact heart.