Engineering Drug-Eluting Ocular Bioadhesive "OcuTAPE" via Tannic Acid-Mediated Nanoparticle Bridging

Dynamic integration of nanoparticles (NPs) into hydrogels remains a key challenge in engineering drug-eluting bioadhesives. A generalizable strategy leveraging the multifunctional binding capacity of tannic acid (TA) to bridge drug-loaded NPs and hydrogel via hydrogen bonding is presented. Acting as both a bioadhesive moiety and dynamic crosslinker, TA enables synthesis-free NP incorporation and facilitates versatile nanocomposite designs for sustained, localized drug delivery. To demonstrate clinical relevance, a ready-to-use ocular patch named 'OcuTAPE' is developed to address the unmet need for bioadhesives that seal injuries and provide sustained drug release. Current ocular adhesives suffer from poor retention, mechanical mismatch, uncontrolled drug release, and limited usability. OcuTAPE achieves high toughness (≈4000 kJ m^-3), rapid wet tissue adhesion without external aids, and TA-mediated integration of poly (ethylene glycol) (PEG)-based micelles (MCs) for dexamethasone (Dex) release over five weeks. The patch conforms to ocular biomechanics, retains in vivo on rabbit and pig eyes, and demonstrates biocompatibility and intrinsic anti-inflammatory efficacy. To illustrate TA-bridging versatility, a second model with drug-loaded poly (lactic-co-glycolic acid) (PLGA) NPs in a gelatin methacryloyl (GelMA)-TA hydrogel is engineered, serving as a naturally derived matrix suitable for tissue regeneration. These findings establish TA bridging as a robust strategy for engineering drug-eluting nanocomposite bioadhesives, with OcuTAPE as a clinically relevant model.