Fundamental, model-driven investigations of structure and physical properties of poly(vinyl alcohol) hydrogels and multi-arm poly(ethylene glycol) hydrogels : decoupling stiffness and solute transport

Abstract

Synthetic hydrogels are advanced biomaterials frequently used in cutting-edge biomedical engineering research and clinical interventions. Their value is highly associated with their tunability and ability to mimic the extracellular matrix properties of a variety of tissues such as bone marrow and brain tissue, but many of the fundamental properties of hydrogels are overly generalized and under-investigated. Recent studies have shown that cells respond to both the stiffness and solute transport profile of their environment, but standard hydrogel synthesis methods cause those two properties to be highly correlated. New insight into structural control of hydrogel properties is needed to independently tune stiffness and solute transport in hydrogels. This dissertation combines fundamental modeling, the full capabilities of multi-arm poly(ethylene glycol) (PEG) hydrogel design, and high-throughput, standardized methods for measuring hydrogel swelling, stiffness, and solute transport to decouple stiffness and solute diffusivity in hydrogels without changing their chemical properties. First, we coordinated equilibrium swelling theory, rubberlike elasticity theory, and mesh transport theory into the fundamental predictive swollen polymer network model. From the model and prior studies relating hydrogel structure and function, we identified four structural parameters that could be independently controlled at synthesis. The swollen polymer network model predicted that simultaneously manipulating these four structural parameters would decouple stiffness and solute diffusivity. Poly(vinyl alcohol) (PVA) hydrogels were used to establish model-compatible, high-throughput measurement methods for swelling, stiffness, and solute transport. The eighteen PVA hydrogel formulations with variation in two of the four structural parameters also served as a control group for the multi-arm PEG hydrogels. The extensive validation studies with PVA hydrogels identified limitations of the swollen polymer network model not addressed by the following multi-arm PEG hydrogel studies, such as how solute diffusivity scales differently with solute size for different solute chemical profiles. Stiffness and solute transport were decoupled by the four structural parameters in multi-arm PEG hydrogels. However, the structure-property relationship that facilitated the decoupling was not predicted by the swollen polymer network model, highlighting an opportunity for further model development. The fundamental model-based hydrogel design approach described here provides a foundation for robust hydrogel design for biomedical applications.Biomedical Engineerin