Date Available

12-7-2011

Year of Publication

2005

Document Type

Thesis

College

Graduate School

Department

Biomedical Engineering

First Advisor

David A. Puleo

Abstract

Biodegradable polymer materials, specifically poly(lactic-co-glycolide) (PLGA) can be used as bone replacements for bone regeneration. Scaffolds can be prepared to be porous to induce bone growth into a scaffold so that it is replaced with natural tissue as the polymer degrades. However, simply using PLGA will result in formation of scar tissue rather than regeneration of natural bone. Therefore focus has turned to attaching growth factors to the PLGA molecules to elicit a specific cellular response when the implant is placed in the body. Site-directed immobilization utilizes specific groups on both the biomaterial and biomolecule so that growth factors can be oriented in a specific manner for increased cellular response. In this research, exposed carboxyl groups on a non end-capped PLGA were modified with bishydrazide spacer molecules of varying length for the eventual attachment of a biomolecule via carbodiimide chemistry. The number of hydrazide groups attached to the surface could be controlled to investigate the effects of the spacer length on protein immobilization. Both vascular endothelial growth factor (VEGF) and parathyroid hormone (PTH) were used in these studies. These two molecules have different target cells and actions, although both can play a role in bone formation. Both molecules have carbohydrate residues that were oxidized with periodate to form aldehyde moieties that were able to react with the hydrazide spacers to form a stable bond between the spacer and protein. The use of a spacer enhanced the binding accessibility of the protein as compared to randomly adsorbed protein. The shortest and longest of the spacers resulted in the highest amount of protein, with corresponding results for antibody binding. The modification of PLGA functional groups with a spacer molecule indicates that this material could be used for site-directed immobilization for any application, simply by tailoring the reaction between the biomaterial and biomolecule.

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