Design Parameters for Injectable Biopolymeric Hydrogels with Dynamic Covalent Chemistry Crosslinks.

Dynamic covalent chemistry (DCC) crosslinks can form hydrogels with tunable mechanical properties permissive to injectability and self-healing. However, not all hydrogels with transient crosslinks are easily extrudable. For this reason, 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). We synthesized several hydrogel families with distinct HA MW and DoF while keeping the ELP-HYD component constant. The resulting hydrogels had a range of stiffnesses, 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, regardless of stiffness. Higher DoF formulations exhibited more rapid self-healing. Gel extrusion through a cannula (2-m length, 0.25-mm diameter) demonstrated the potential for minimally-invasive delivery for future biomedical applications. In summary, this work highlights additional parameters that influence the injectability and network formation of DCC-crosslinked hydrogels and aims to guide future design of injectable hydrogels. This article is protected by copyright. All rights reserved.