| The work described in this thesis focuses on the design, synthesis, and characterization of novel polyphosphazenes for advanced biomedical applications. In addition, the fabrication of polyphosphazene / poly(lactic-co-glycolic acid) (PLGA) blends were examined for their physical properties as hard tissue engineering scaffolds.;Chapter 2 discusses the synthesis of the dipeptides alanyl-glycine ethyl ester, valinyl-glycine ethyl ester, and phenylalanyl-glycine ethyl esters. The alanyl-glycine ethyl ester replaced all the chlorine atoms in poly(dichlorophosphazene). However, replacement of all the chlorine atoms in poly(dichlorophosphazene) by valinyl-glycine ethyl ester or phenylalanyl-glycine ethyl ester polyphosphazenes was prevented by the insolubility of the partially substituted intermediates. To circumvent this problem, co-substitution was carried out using the valinyl- or phenylalanyl esters with glycine ethyl ester or alanine ethyl ester in a 1:1 ratio. Co-substituted polyphosphazenes with alanyl glycine ethyl ester and glycine ethyl ester or alanine ethyl ester were also synthesized with a side group ratio of 1:1.;Chapter 3 outlines the preparation of phosphazene tissue engineering scaffolds with bioactive side groups using the biological buffer choline chloride. The phosphazene structures and physical properties were studied using multinuclear NMR, differential scanning calorimetry (DSC), and GPC techniques. The resultant polymers were then blended with PLGA (50:50) or PLGA (85:15) and characterized by DSC analysis and scanning electron microscopy (SEM). Polymer products obtained via the sodium hydride route produced miscible blends with both ratios of PLGA, while the cesium carbonate route yielded products with reduced blend miscibility.;Chapter 4 describes the preparation of phosphazenes that possess reversible cross-linking groups to control mechanical stability and hydrolysis using cysteine and methionine amino acid side groups. Small molecule models and linear polymeric phosphazenes that contain methionine ethyl ester and cysteine ethyl disulfide ethyl ester side groups were synthesized. Protection of the free thiol groups was carried out to circumvent unwanted cross-linking of the phosphazenes through the cysteine ethyl ester N- and S-termini. Cyclic trimeric cysteine ethyl disulfide ethyl ester model compounds were deprotected by S-S bond cleavage using beta-mercaptoethanol, dithiothreitol (DTT), and zinc in aqueous hydrochloric acid.;Chapter 5 evaluates the first reported synthesis of a completely hydrolysable polyphosphazene-containing block co-polymer. The synthesis of poly(lactic acid)-co-poly[(bis-alanine ethyl ester phosphazene)], poly(lactic acid)-co-poly[(bis-valine ethyl ester phosphazene)], and poly(lactic acid)-co-poly[(bis-phenylalanine ethyl ester phosphazene)] has been accomplished. These block co-polymers were used as blend compatibalizers to form composites of PLAGA (50:50) or PLAGA (85:15) with poly[(bis-alanine ethyl ester phosphazene)], poly[(bis-valine ethyl ester phosphazene)], or poly[(bis-phenylalanine ethyl ester phosphazene)].;Chapter 6 discusses a unique polymer erosion process for biodegradable biomaterials through which the polymer changes from a solid coherent film to an assemblage of microspheres with interconnected porous structures. The polymer system was developed on the highly versatile platform of self-neutralizing polyphosphazene-polyester blends. Co-substituting a polyphosphazene backbone with both glycylglycine dipeptide and with side groups that can retard the polymer degradation, such as hydrophobic 4-phenylphenoxy, generated a unique polymer with strong hydrogen bonding ability and a slow degradation rate.The blend degradation was further investigated in vivo using a rat subcutaneous implantation model.;Chapter 7 describes a series of closely related polyphosphazenes with propoxy, pentoxy, hexoxy, octoxy, isostearyloxy, and 2-(2-methoxyethoxy)ethoxy (MEE) side groups, together with co-substituent species with both the alkoxy and MEE side chains. These were studied for their morphology and miscibility with oligoisobutylene (OIB). When both alkoxy and MEE side groups were present, the solubility in OIB was also low (0-3%), except for the species with both isostearyloxy and MEE side groups, which was soluble in OIB at a level of 21 wt/wt% at 80°C, and showed Tg evidence of polymer/oligomer miscibility even at -80°C. Explanations are suggested for the unusual behavior of this polymer. (Abstract shortened by UMI.)... |
