CONTROLLED RELEASE FROM A BIODEGRADABLE ELASTOMER FOR APPLICATIONS IN CARDIOVASCULAR REGENERATIVE MEDICINE

Insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) have been implicated in the intrinsic response of the heart to myocardial infarction (MI), and it has been postulated that exogenous administration of one or both of these growth factors may enhance myocardial repair and regeneration. We hypothesized that a biodegradable, elastomeric poly(ester urethane)urea (PEUU) capable of sustained, local delivery of IGF-1 or HGF to ischemic myocardium would improve left ventricular (LV) dimension and function. PEUU scaffolds without growth factor or scaffolds containing either IGF-1 or HGF were applied onto the hearts of rats injured by MI. Improvement in LV function and restoration of LV wall thickness, muscle mass, and angiogenesis were assessed 8 weeks post-patch implantation. Improvement in LV dimension and function due to IGF-1-loaded patches was not significant compared to control patches, while HGF-loaded patches significantly worsened LV dimension compared to IGF-loaded and control patches. No significant differences in muscle or capillary formation or LV function were noted between groups. Although no significant improvements were noted with growth factor-loaded patches, trends towards improved LV dimension with IGF-1-loaded patches and trends towards worsened LV dimension and function with HGF-loaded patches may warrant additional investigation.Furthermore, we evaluated the ability of PEUU to deliver molecules deigned to induce cellular gene expression in a spatially-controlled manner in vitro. PEUU films and scaffolds with spatially-defined regions containing or omitting inducer molecules were fabricated, and cells transduced to express green fluorescent protein (GFP) were cultured on films and within scaffolds to evaluate spatial control of gene expression. PEUU demonstrated an extended period of controlled release of the inducer molecule as well as providing spatial control over GFP expression in both PEUU films and three-dimensional scaffolds. Hence, these scaffolds may provide a means to control progenitor cell commitment in a spatially-defined manner in vivo for tissue repair and regeneration. With an elastic scaffold delivery system, such a technique might ultimately find application in cardiovascular tissue engineering