Changes in Polymer, Scaffold, and IGF-I Delivery Methods Directly Affect Cartilage Tissue Development: A Dissertation

As cartilage tissue has limited repair capacities, tissue engineering has emerged as a promising alternative for cartilage repair. The scaffold is a primary component of the tissue engineerig design, yet little inormation exists regarding the effects of polymer and scaffold properties on tissue growth. In this study, we have developed a novel scaffold, PLG micro spheres, for use in cartilage tissue engineerig, which has the capacity for alterations in polymer and scaffold. We examed the effects of molecular weight, hydrophobic capping, delivery ofMg(OHh microsphere size, and controlled release oflGF-I. Our fmdings demonstrated that polymer parameters distinctively affect tissue and matrx output. Specifcally, micro spheres with high molecular weight polymer produced tissue with high GAG content and tissue mass in vivo and in vitro, while micro spheres with capped polymer induced steady tissue and matrx accumulation, but may have precluded cell attachment. Release of buffer to the growing cartilage had negative effects on tissue formation in vivo and in vitro. Additionally, increasing microsphere diameter generated more samples with center of necrotic tissue. The presence of micro spheres induced greater carlage mass and matrx content than cartilage from cells alone. Delivery oflGF-I induced a dose-dependent effect on matrx and tissue production in vivo, with the highest effective load oflGF-I (0.3%) generating the most matrx and tissue accumulation. In contrast, the in vitro IGF-I dosedependent effect induced on matrix and tissue production peaked at a dose of 0.02% IGFwith higher doses generating less tissue and matrx. Taken together, changes in polymer or scaffold composition and release of growth factor can be optimzed to form carilage with enhanced tissue parameters. Moreover, these results demonstrate a novel scaffold with potential to support carilage regeneration and provide simultaneous drug delivery.