(455d) Microrheological Measurement of the Degradation of Covalently Adaptable Hydrogel Scaffolds

Synthetic hydrogel scaffold are designed for a broad array of applications, including wound healing, tissue regeneration and 3D stem cell culture platforms. The lack of knowledge of the material microstructure and its effect on the performance of the scaffold is a growing challenge especially in complex matrices. Covalently adaptable (CA) hydrogels mimic the native extracellular matrix that cells experience in vivo due to their ability to physically adapt to their environment. The CA hydrogels we are studying is made from multi-arm poly(ethylene glycol) (PEG) molecules that form reversible bis-aliphatic hydrazone bonds. This unique chemistry creates a material that yields when a stress is applied and reforms covalent bonds once the stress is released. In this work, we use multiple particle tracking microrheology (MPT) to measure dynamic material properties during scaffold degradation due to a change in pH or shift in reaction equilibrium. MPT measures the thermal motion of embedded probe particles to extract rheological properties using the Generalized Stokes-Einstein Relation. The CA hydrogel in a pH 4.3 buffer degrades over 2 days and has a smooth transition through time from a gel to a sol. Reverse time-cure superposition is used to pinpoint the critical degradation time, t_c=0.3 days, and critical relaxation exponent, n=0.43. The pH 7.1 progresses through the gel-sol transition, but breaks and reforms bonds throughout the entire gelation reaction until complete dissolution of the matrix occurs. This occurs over a much longer time scale, on the order of tens of days. These measurements also show that the scaffold degrades homogeneously throughout the entire process, determined from an ensemble-averaged van Hove correlation function. In depth information about the material microstructure will enhance design of implantable scaffolds that accelerate tissue regeneration by enabling facile motility and differentiation of encapsulated cells.