(495a) Design Parameters for Injectable Biopolymeric Hydrogels with Dynamic Covalent Chemistry Crosslinks

Dynamic covalent chemistry (DCC) is a promising approach to crosslink hydrogels with tunable mechanical properties permissive to injectability. However, these transient bonds cannot universally predict the ease of hydrogel extrusion and self-healing. For this reason, we hypothesized that two additional design parameters must be considered when formulating DCC-crosslinked hydrogels: 1) degree of functionalization (DoF) and 2) polymer molecular weight (MW). To investigate these parameters, we formulated hydrogels comprised of two recombinant biopolymers: (1) a hyaluronic acid (HA) modified with benzaldehyde (HA-BZA) and (2) an elastin-like protein (ELP) modified with hydrazine (ELP-HYD). When these biopolymers are mixed, a hydrogel network is rapidly formed. This platform is uniquely suited to explore the chosen parameters, as the DoF on the ELP-HYD can be maintained constant while altering the HA MW (20, 40, 60, and 100 kDa) and DoF (6, 12, 20, and 30 %) to synthesize a large family of hydrogels. The resulting hydrogels had a wide range of stiffness (G’ ~ 10-1000 Pa) and extrudability, which was attributed to the combined effects of DCC crosslinks and polymer entanglements. In general, lower MW formulations required lower forces for injectability, even for stiffer hydrogels. Formulations with higher DoF exhibited more rapid self-healing. These observations allowed us to develop new design rules for the synthesis of injectable gels. Applying these design rules, we demonstrated the ability to hand-inject an optimized hydrogel formulation through a long, narrow cannula (2-m length, 0.25-mm diameter), suggesting that these materials have strong clinical potential for medical applications involving catheter delivery.