Injectability of Biosynthetic Hydrogels: Consideration for Minimally Invasive Surgical Procedures and 3D Bioprinting

Injectable hydrogels are often preferred when designing carriers for cell therapy or developing new bio-ink formulations. Biosynthetic hydrogels, which are a class of materials made with a hybrid design strategy, can be advantageous for endowing injectability while maintaining biological activity of the material. The chemical modification required to make these gels injectable by specific crosslinking pathways can be challenging and also make the hydrogels inhospitable to cells. Therefore, most efforts to functionalize biosynthetic hydrogel precursors toward injectability in the presence of cells try to balance between chemical and biological functionality, in order to preserve cell compatibility while addressing the injectability design challenges. Accordingly, hydrogel crosslinking strategies have evolved to include the use of photoinitiated "click" chemistry or bio-orthogonal reactions with rapid gelation kinetics and minimal cyto-toxicity required when working with cell-compatible hydrogel systems. With many new injectable biosynthetic materials emerging, their impact in cell-based regenerative medicine and bioprinting is also becoming more apparent. This review covers the main strategies that are used to endow biosynthetic polymers with injectability through rapid, cyto-compatible physical or covalent crosslinking and the main considerations for using the resulting injectable hydrogels in cell therapy, tissue regeneration, and bioprinting.