Hydrogel-Based Injectable Therapies

Abstract

Injectable hydrogels -- water-swollen polymer networks that undergo sol-gel transition in situ after injection -- are emerging as versatile platforms for minimally invasive tissue repair, localised drug delivery, and cell transplantation. Unlike preformed scaffolds requiring surgical implantation, injectable hydrogels flow through standard gauge needles (18-27G) and conform to irregular tissue defects, gelling within seconds to minutes at the injection site through thermal, ionic, enzymatic, or photo-initiated crosslinking. The clinical applications span orthopaedics (cartilage defect filling, bone void augmentation), cardiology (post-infarction ventricular support), ophthalmology (vitreous substitution), and oncology (localised chemotherapy depots). Yet the design space is vast: natural versus synthetic polymers, physical versus chemical crosslinking, degradable versus non-degradable networks, drug-loaded versus cell-laden formulations. We present the Injectable Hydrogel Therapy Assessment Framework (IHTAF), evaluating five hydrogel platforms - hyaluronic acid-tyramine (HA-Tyr) enzymatic gels, alginate-calcium ionic gels, PEG-based photo-crosslinked gels, self-assembling peptide (SAP) gels, and thermoresponsive PNIPAM-based gels -- across four clinical applications (cartilage repair, myocardial injection, vitreous replacement, and intratumoral chemotherapy). Our Hydrogel Therapy Performance Score (HTPS) measures injectability, gelation kinetics, mechanical match to target tissue, therapeutic payload delivery, and biocompatibility. HA-Tyr enzymatic gels achieve the highest HTPS (0.928) through tunable gelation, excellent biocompatibility, and native tissue mimicry for cartilage and vitreous applications, while PEG photo-crosslinked gels achieve the most precise spatial control (0.960) for applications requiring patterned architectures.