In vivo biocompatibility and immunogenicity of metal-phenolic gelation.

forming hydrogels are of interest for diverse biomedical applications due to their ease-of-use and minimal invasiveness and therefore high translational potential. Supramolecular hydrogels that can be assembled using metal-phenolic coordination of naturally occurring polyphenols and group IV metal ions (e.g. Ti or Zr) provide a versatile and robust platform for engineering such materials. However, the formation and response to this new class of materials has not yet been reported. Here, we demonstrate that metal-phenolic supramolecular gelation occurs successfully and we investigate the host response to the material over 14 weeks. The Ti-tannic acid materials form stable gels that are well-tolerated following subcutaneous injection. Histology reveals a mild foreign body reaction, and titanium biodistribution studies show low accumulation in distal tissues. Compared to poloxamer-based hydrogels (commonly used for gelation), Ti-tannic acid materials show a substantially improved drug release profile for the corticosteroid dexamethasone (from <1 day to >10 days). These results provide essential characterization for this new class of metal-phenolic hydrogels, and highlight their potential suitability for biomedical applications in areas such as drug delivery and regenerative medicine.