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

Abstract

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 engineering design, yet little information exists regarding the effects of polymer and scaffold properties on tissue growth. In this study, we have developed a novel scaffold, PLG microspheres, for use in cartilage tissue engineering, which has the capacity for alterations in polymer and scaffold. We examined the effects of molecular weight, hydrophobic capping, delivery of Mg(OH)2, microsphere size, and controlled release of IGF-I. Our findings demonstrated that polymer parameters distinctively affect tissue and matrix output. Specifically, 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 matrix 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 microspheres induced greater cartilage mass and matrix content than cartilage from cells alone. Delivery of IGF-I induced a dose-dependent effect on matrix and tissue production in vivo, with the highest effective load of IGF-I (0.3%) generating the most matrix and tissue accumulation. In contrast, the in vitro IGF-I dose-dependent effect induced on matrix and tissue production peaked at a dose of 0.02% IGF-I, with higher doses generating less tissue and matrix. Taken together, changes in polymer or scaffold composition and release of growth factor can be optimized to form cartilage with enhanced tissue parameters. Moreover, these results demonstrate a novel scaffold with potential to support cartilage regeneration and provide simultaneous drug delivery.