Date of Award

1-1-2009

Document Type

Campus Access Thesis

Department

Biomedical Engineering

First Advisor

Esmaiel Jabbari

Abstract

Polymers, as hydrogel macromers, have been studied and widely applied to develop scaffolds in tissue engineering since 1990s, because they offer a number of advantages over other materials such as the ability to tailor mechanical properties and degradation kinetics based on various applications. Among these synthetic polymers, poly(lactide-co-glycolide) (PLGA) copolymers have been popularly used either as temporary scaffolds for cell transplantation to regenerate tissues or as drug carriers for delivery of bioactive molecules. Our laboratory has done researches in developing hydrogel scaffolds for bone regeneration for over 5 years, including PLGA polymer synthesis and characterization, mechanical properties, degradation and swelling rate, embedding nanoparticle as drug carrier, chemical modification on hydrogel substrate with osteogenic differentiation factors of marrow stromal cells. In this thesis, the main result of my research work has been the development of injectable macromer star-poly(lactide-co-glycolide-co-acrylate) (PLGAA). Thus, the goals of work are synthesis design, macromer characterization, studies of hydrogel physical properties including water content and degradation characteristics, and study of hydrogel rheological properties.

We develop 4-arm PLGAA macromers synthesized by ring-opening polymerization method. Nuclear magnetic resonance (NMR) and gel permeation chromotography (GPC) are used to characterize polymer chemical structure and molecular weight distribution. Chapter three presents the synthesis method and results of NMR and GPC. Averagely, 2.5-3 units of lactides and glycolides are randomly added to the arms of macromer. The end of each arm is linked with a vinyl group which can function in cross-linking into hydrogel or being modified by other functional groups. The Number average molecular weight (Mn) of PLGA is 2.5KDa.

In chapter four, degradation and swelling profiles, and mechanical property were studied. The degradation and swelling of hydrogel prepared by star-shaped PLGAA macromers can be controlled by adjusting ratio of LA to GA. GA is more hydrophilic than LA. Increasing GA content in PLGAA macromer can improve swelling characteristic of hydrogel. Furthermore, degradation of hydrogel containing more GA will be faster. Hydrogel prepared by 50/50 PLGAA was completely degraded within 9 weeks, while hydrogel prepared by 75/25 PLGAA lost 50% of original weight during the same period. Factors affecting rheological properties of the hydrogel include fractions of cross linker N-vinyl-2-pyrrolidone, fractions of photoinitiator Irgacure 2959, and water content. In this research work, the effects of these factors on gelation time and ultimate storage modulus have been experimentally determined. Generally, the effects of photoinitiator are not obvious. Water content and NVP in hydrogel precursor solution are the most important factors on rheological properties of hydrogel. The maximum G'ult is 2MPa. The gelation time is around 40 seconds. These results greatly contribute to further study of for bone marrow stromal cell differentiation and proliferation, even for bone regeneration and wound healing.

Rights

© 2009, Jianping Wu

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