Master's Thesis Defense - Super-Porous PVA Hydrogel with the Controlled Release of IGF-1 for Cartilage Tissue Engineering
Date: June 26, 2012
Time: 10:30 AM
Location: Bossone Research Enterprise, Room: 709
Advisors: Fred Allen, Ph.D., Margaret Wheatley, Ph.D., Kara Spiller, Ph.D., and Tony Lowman, Ph.D.
Repair or regeneration of articular cartilage remains one of the most difficult challenges in orthopedic medicine. Poly(vinyl alcohol) (PVA) hydrogels have shown promise as synthetic cartilage replacement materials, especially those that allow sustained release of insulin-like growth factor 1 (IGF-1). The goal of this study was to increase the porosity of the hydrogels while maintaining IGF-1 release in order to increase infiltration of chondrocytes from surrounding cartilage. The hydrogels were prepared using a previously established, single step, double emulsion technique based on a water-oil-water (W1/O/W2) composition. IGF-1 was encapsulated in degradable poly(lactic-co-glycolic acid) (PLGA) microparticles (W1/O) embedded in non-degradable poly(vinyl alcohol) (PVA) hydrogels (W2). The effects of processing parameters such as volume and composition of the water and oil phases were evaluated towards increasing hydrogel porosity. Hydrogels of various formulations had interconnected pores with an average pore size of as high as 337±205um, with the largest range of pore sizes from 40um to 600um, and porosities of 76% to 84%, all of which were increases over the previous design. The controlled release system sustained release of IGF-1 for 73 days in vitro, with an initial burst on the first day of 1.82 ± 1.15ug. In order to study the controlled release of IGF-1 on cartilage tissue engineering in vivo, the hydrogels were seeded with chondrocytes and implanted subcutaneously into the backs of nude mice and harvested after two and five weeks in vivo. The introduction of high levels of porosity to PVA hydrogels resulted in a reduction in mechanical properties but an increase in cartilage growth within the hydrogels. This study shows that the sustained release of IGF-1 can enhance tissue formation within the pores of a non-degradable hydrogel. The increase in porosity of the IGF1-eluting hydrogels may improve implant integration with surrounding tissue.
The Bossone Research Enterprise Center is located at the corner of 32nd and Market Streets.