| A growing number of applications in the biomedical and pharmaceutical fields rely upon material properties unique to biodegradable, crosslinked hydrogels. The success or failure of these devices in such critical applications is therefore determined by the performance of the highly swollen, yet durable, systems during their degradation. However, relationships between the macroscopic properties of these gels and their constantly changing microscopic characteristics are not straightforward, and their degradation behavior is difficult to predict. Networks based on degradable PLA-b-PEG-b-PLA crosslinkers were specifically tailored and used as a model system to provide a general framework for investigating the process of bulk-degradation in crosslinked gels. The degradation behavior of swollen, crosslinked hydrogels was initially characterized through measurements of swelling and compressive modulus in these systems. The influence of various chemical, environmental, and processing parameters on the macroscopic behavior of the gels was also studied. A degradation mechanism assuming pseudo first-order hydrolysis kinetics and accounting for the structure of the crosslinked networks successfully predicted the experimentally observed trends in these properties with degradation. Understanding the controlling factors behind the degradation of crosslinked gels allows networks to be specifically tailored for desired applications such as controlled release matrices. Thus, once verified, the proposed degradation mechanism was extended to correlate polymer degradation kinetics, and subsequent changes in network structure, with release behavior of bioactive molecules from these dynamic systems.; Finally, a theoretical model utilizing a statistical approach to predict the cleavage of crosslinks within the network was developed to predict the complex erosion profiles produced by these hydrogels. These profiles were shown to depend on the hydrolysis rate constant, the number of crosslinks per backbone chain, and other structural and chemical parameters. Model predictions were validated through comparisons to mass-loss observations. Analysis of degradation products using MALDI and GPC provided an additional method to validate model predictions, as well as to investigate the structure of crosslinked networks. |
