Dynamic Changes in Material Properties and Degradation of Poly(ethylene glycol)–Hydrazone Gels as a Function of pH

Abstract

Covalent adaptable hydrogels (CAHs) dynamically evolve when pushed out of equilibrium by force or change in environmental conditions. Adapting these materials for advanced biological applications, including 3D cell culture and drug delivery platforms, requires in-depth knowledge of the evolution of scaffold microstructure and rheological properties. We use multiple particle tracking microrheology to measure the changes in a poly­(ethylene glycol)–hydrazone CAH structure and properties when pushed out of equilibrium by a single change in pH. We determine the CAH degrades rapidly at acidic pH with multiple cycles of almost complete degradation and gelation. At pH 7.1, the scaffold degrades and re-forms cross-links over approximately 1.5 weeks with small oscillations between degradation and gelation. These degradation cycles are well described with first- and second-order reaction kinetics. MPT is sensitive enough to measure the phase transitions in these materials giving new insight into how CAHs evolve and their potential uses in biological applications.

A Recent Perspective on Noncovalently Formed Polymeric Hydrogels

“…There is bond breakage and hysteresis in bond reformation, leading to the scaffold degrading slowly over 1.5 weeks. This study provides a better understanding of degradation of these hydrazine linkages . It is also possible to tune the degradability of dynamic hydrogels from less than 24 h to more than 7 days by changing the proportion of the more stable oxime linkages and the less stable hydrazine linkage ,…”

Microrheological characterization of covalent adaptable hydrogels for applications in oral delivery

“…Probe particles are isotropically suspended within this scaffold to enable microrheological measurement. Previous investigations characterized swelling, cell encapsulation, gelation kinetics and viability in this hydrogel scaffold 1,12,17 . The rheology of this hydrogel was previously measured and the unswollen equilibrium moduli is reported to be approximately 30 kPa 12,17 .…”

“…At equilibrium, CAHs are stable and behave like conventional covalent cross-linked hydrogels. Bond breakage and reformation is triggered when stimuli pushes the material out of equilibrium [1][2][3][4][5][6][7] . These environmental and external stimuli include temperature, light, electromagnetic fields, pH and mechanic forces 1,[8][9][10][11][12][13][14][15][16] .…”

“…Bond breakage and reformation is triggered when stimuli pushes the material out of equilibrium [1][2][3][4][5][6][7] . These environmental and external stimuli include temperature, light, electromagnetic fields, pH and mechanic forces 1,[8][9][10][11][12][13][14][15][16] . Due to this, CAHs have a wide range of biological applications including platforms for three-dimensional (3D) cell encapsulation and culture 12,14,17,18 , wound healing and tissue regeneration 11,[19][20][21][22][23] and drug delivery 14,20,21,[24][25][26][27] .…”

“…The pH-responsiveness of this scaffold makes it a material that would undergo dynamic transitions in physiologically relevant environments. Previous studies have characterized the pH-dependent degradation and gelation of this PEG-hydrazone CAH 1,12,17,35 . This work indicates scaffold degradation and, subsequently, release of functional molecules from this material can be tuned by changing the environmental pH.…”