Biocompatibility analysis and biomedical device development using novel L-tyrosine based polymers.

摘要

L-tyrosine based 'pseudo' poly (amino acids) such as polyphosphates and polyurethanes have been developed using desaminotyrosine tyrosyl hexyl ester (DTH) as the monomer, and characterized with the aim of using them for biomedical applications. The successful establishment of the biocompatibility of these novel materials is critical for their success and acceptance in the biomedical device field. One of the main aims of the research presented in this dissertation has been to evaluate the biocompatibility of novel L-tyrosine based polymers and their degradation products by examining their cytotoxicity, investigating the adhesion and proliferation of human fibroblast cells on L-tyrosine based polymeric substrates, and correlating the cell adhesion to surface wettability and composition of the substrates.;Characterization results of L-tyrosine based polyurethanes and polyphosphate have shown that although these polymers are synthesized using a common monomer, they exhibit dramatically different physico-mechanical properties. Another aim of this dissertation has been to examine the blending of polyphosphate and polyurethanes in order to develop materials with a wider spectrum of physico-mechanical properties and thus obtain a stepwise transition in the material properties by adjusting the blends composition. The blends have been extensively characterized for different bioengineering properties including surface and bulk characteristics. In addition, the possibility of application of polyphosphate and polyurethanes for the formulation of controlled drug delivery devices has been investigated. Drug delivery devices in the form of microparticles and electrospun micro- and nano-fibrous membranes have been developed and certain process parameters associated with the formulation process have been optimized.;The results indicate that L-tyrosine based polymers and their degradation products are non-cytotoxic under test conditions (dosages and time frames examined). The adhesion of cells onto L-tyrosine based polymeric substrates has been found to be a function of the polymer chemistry and its surface wettability. Polymers with moderate hydrophobicity have been found to promote cellular adhesion whereas hydrophilic surfaces retarded cellular adhesion and proliferation. These results coupled with the physico-chemical and mechanical properties of these novel polymers suggest that they are prospective candidates for biomedical applications including tissue engineering and drug delivery devices. Further, results obtained from blend characterizations indicate that the material properties of blends are a strong function of the blend composition and blending of polyphosphate and polyurethanes provides an easy way to obtain materials with a wide range of properties intermediate to the parent polymer properties. Finally, the successful development of drug delivery devices in the form of microparticles and micro- and nano-fibrous membranes has shown that these novel materials can indeed prove to be a very valuable addition to the existing arsenal of biomaterials.