Design and synthesis of polyphosphazenes: Hard tissue scaffolding biomaterials and physically crosslinked elastomers

The work in this thesis is divided into two main parts. The first part examines the synthesis and characterization of polyphosphazenes as potential scaffolding materials usable for hard tissue repair. The goal of this work was to design polymers containing acidic functional groups in an attempt to encourage the deposition of calcium hydroxyapatite when the polymer is exposed to simulated body fluids. The second part examines the development of a new polymeric architecture which generates elastomeric properties without the use of traditional covalent or physical crosslinks. The goal was to examine the effects of this new architecture on the physical and mechanical properties of the final polymers.;Chapter 1 provides a general background for the two main focus areas mentioned above. More specifically: a brief explanation is provided of the necessary physical and chemical properties of a suitable hard tissue engineering scaffolding substrate, and the basis of those requirements; together with an examination of the traditional ways in which elastomeric properties are introduced into a polymeric sample.;Chapter 2 details the design and synthesis of polyphosphazenes bearing phosphonic acid and phosphoester side groups using two different routes. The first route utilized a linker unit which was functionalized with phosphoesters prior to its attachment to the polyphosphazene backbone, while the second route involved attachment of the same linking group to the polyphosphazene backbone before the introduction of the phosphoester moieties. In both cases, the samples were treated with iodotrimethylsilane to cleave the ester bonds and afford the parent phosphonic acid. Both routes proved successful. However, varying difficulties were encountered for each route.;In Chapter 3 we examine the ability of the phosphonic acid functionalized polyphosphazenes described in Chapter 2 to mineralize calcium hydroxyapatite when exposed to simulated body fluid, which has the same ion concentration as human blood plasma. Scanning electron microscopy studies revealed that those polymers which were synthesized by phosphonation of the linker group after its attachment to the polymer backbone had a higher degree of inorganic deposition along the surface. However, these polymers had a lowed overall concentration of phosphonate groups per polymer chain. The inability to fully remove the ester protecting groups proved to be a key driving force for this increased activity. In addition, Time of Flight Secondary Ion Mass Spectroscopy (ToF-SIMS) analysis was utilized along with X-ray scattering to provide confirmation that the deposited phase was calcium hydroxyapatite, the natural mineral of bone.;Chapter 4 describes the development of a family of carboxylic acid functionalized polyphosphazenes and the examination of their ability to mineralize calcium hydroxyapatite when exposed to simulated body fluids. The acid moieties in this system are introduced by the incorporation of the allyl esters of beta-alanine or gamma-amino butyric acid, followed by deesterification to afford the parent carboxylic acid. These samples show a significant increase in their ability to nucleate the growth of calcium hydroxyapatite along their surface, with the best sample doubling in mass within 4 weeks, which is a major improvement over the phosphonic acid functionalized samples described in Chapter 3.;Chapter 5 contains an account of a new polymer architecture which imparts elastomeric properties without the use of traditional covalent or physical crosslinks. The polymers were synthesized with sterically bulky cyclotriphosphazene side groups linked directly to the polyphosphazene backbone using a hydroquinone linker. The geometry of the linking unit, as well as the large bulk of the side groups themselves, allowed the cyclotriphosphazene units to protrude away from the polymer backbone in a manner similar to the oars on a Viking long ship. This allowed them to interact physically with the oar's on adjacent polymer chains, and lock the chains in place, similar to the way in which the oars on one ship will interdigitate with the oars of another ship if they get too close.;Chapter 6 expands the chemistry of the non-traditional elastomers described in Chapter 5. Specifically, the substituent groups on the cyclotriphosphazene groups are changed from 2,2,2- trifluoroethoxy to phenoxy, while the remaining chlorine atoms along the polymer backbone are still replaced with 2,2,2-trifluoroethoxide. The new polymers are shown to have better mechanical properties then the polymers described in Chapter 5.;Chapter 7 describes a further extension of the ideas in Chapters 5 and 6. Specifically it involves the synthesis and mechanical testing of polyphosphazenes bearing oligo-p-phenylene groups co-substituted with 2,2,2-trifluoroethoxide. The oligo-phenylene groups are incorporated to act as variable length cross-linking moieties to further expand the new family of non-traditional polyphosphazene elastomers. The mechanical and physical properties of these polymers reveal a strong dependence on both the length and concentration of the oligo-phenylene minor co-substituent groups. (Abstract shortened by UMI.).