Photocrosslinkable Hyaluronic Acid-Based Hydrogels for In Situ Drug Delivery and Biomedical Applications

Localized drug delivery and minimally invasive treatment require biomaterials that can be formed in situ while providing spatial control over material localization and therapeutic drug release. Here, we developed a photocrosslinkable platform based on glycidyl methacrylate-modified hyaluronic acid (GMA-HA) for in situ hydrogel formation under mild conditions.

Two photoinitiation strategies were investigated to enable selectable, tissue-depth-adapted activation. UV-mediated crosslinking at 365 nm using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) enabled rapid gelation of GMA-HA formulations. To expand the platform toward less superficial applications, a red-light-activated system operating at 660 nm was developed using a phosphorus phthalocyanine/β-mercaptoethanol initiating pair. Incorporation of the cationic porphyrin [(TPP)P(OEt)]⁺Br⁻ was required to achieve high gel-volume conversion and additionally enabled fluorescence-based tracking of hydrogel localization through the skin using 450 nm excitation.

The LAP-based UV-crosslinked formulation was further evaluated in vivo: application to critical-size calvarial defects in Balb/c mice demonstrated substantial defect coverage (quantified by micro-CT) and low local inflammation, assessed by histology, supporting its suitability for in situ biomedical applications.

Overall, the developed GMA-HA photocrosslinking systems provide selectable photoactivation (UV and red light) and in situ hydrogel formation with potential for localized therapeutic delivery, sustained release, and optical monitoring. The combination of hyaluronic acid-based biomaterials with visible-light activation may provide a versatile platform for minimally invasive drug delivery and potential theranostic applications.