The native extracellular matrix (ECM) possesses complex viscoelastic mechanical properties. Changes in these dynamic mechanical properties can control cell fate, yet few synthetic strategies exist to mimic and control these complex properties. There is a clear need in tissue engineering for hydrogel systems with robust control over static (stiffness), dynamic (relaxation), and process-related (printability) mechanical properties. Dynamic covalent chemistry (DCvC) is a promising tool to meet these needs, providing the time-dependent viscoelasticity that covalent crosslinks lack. Here, we leverage the molecular constants of the reversible crosslinking reaction (Keq, k1, k-1) to tune the mechanical properties of hydrogels based on Schiff base crosslinkers with aldehyde-functionalized polymers, while maintaining physiological pH and salinity. We explore how changing the crosslinker's structures, and mixing two distinct crosslinkers, allows us to create 3D bioprinted constructs and control cell behavior using rheology, self-healing tests, extrusion printing, and culture/bioprinting of primary human dermal fibroblasts. Our results show that slight chemical variation of the crosslinker leads to Keqs spanning 101–103 L.mol-1, with corresponding shear moduli spanning 2 decades. Notably, all formulations flow similarly after network rupture, separating the initial mechanical properties from flow behavior during printing. We then target specific mechanical regimes (applications) and ultimately produce 3D printable bioinks with varied cell-instructive mechanical microenvironments. These results show a versatile structure-property-application approach to bottom-up hydrogel engineering. This facile approach highlights reversible Schiff bases as a platform for the design of novel hydrogels using molecular constants, is of interest for targeting viscoelastic properties of cellular niches, and is an accessible platform for designing dynamic networks.

From molecular constants to hydrogel mechanics: Engineering tunable dynamic Schiff base hydrogels enables 3D bioprinting

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.