Synthesis and characterization of in situ forming polyanhydride networks for orthopaedic applications

Numerous musculoskeletal injuries could benefit from the development of a mechanically durable, slow degrading, and in situ forming synthetic polymer to support the healing of bone as remodeling and resorption occur. To this extent, a novel class of photopolymerizable anhydride monomers, which reacts to form highly crosslinked and surface eroding networks, was rationally designed, synthesized and characterized. The photopolymerization behavior and reaction kinetics of the methacrylate anhydride monomers under simulated in vivo conditions were investigated with differential scanning calorimetry and infrared spectroscopy to determine the clinical feasibility of forming the polyanhydride networks in situ.; Rates of surface erosion were monitored by following network mass loss at 37°C. The degradation times for disks (∼1 mm thick) varied from 2 days to ∼1 year by simple changes in monomer backbone chemistry and hydrophobicity. In addition, surface photografting and bulk modification methods were developed to provide control over additional degradative properties (e.g., direction of the surface erosion front) and material properties (e.g., porosity), without compromising the ability to form these materials in situ.; The methacrylated monomers developed in this thesis exhibit the reaction complexities of other multifunctional monomers but form degradable networks. Thus, crosslinked polyanhydride networks can be used to gain fundamental insight into the microstructure of crosslinked polymers (e.g., kinetic chain lengths) by measurement of the linear polymer degradation products. Matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy was used to characterize the absolute molecular weight distribution of the kinetic chain lengths as a function of network evolution, rate of initiation and monomer size. In addition, a kinetic gelation simulation was used to model multifunctional monomer polymerizations and simulate kinetic chain lengths for comparison to trends discovered with experimental data.; Finally, the biocompatibility of the proposed biomaterials was extensively examined using neonatal rat calvaria in vitro and in vivo subcutaneous implants. In addition, a defect was created in the proximal tibia for determining the feasibility of forming the crosslinked polymers in vivo and to examine any adverse effects due to the photopolymerization reaction.