Micelles Embedded Layer-by-Layer Coating with Catechol and Phenylboronic Acid for Tunable Drug Loading, Sustained Release, Mild Tissue Response and Selective Cell Fate for Re-endothelialization.

Tunable/sustained drug loading/releasing are of significance in addressing low cytotoxicity, long-term performance and localized mild healing response in biomedical applications. With an ingenious design, a self-healing sandwiched layer-by-layer (LBL) coating was constructed by using chitosan/heparin as the adopted polyelectrolytes with embedding of micelles, in which chitosan backbone was grafted with catechol and the micelle was modified with exposed phenylboronic acid, endowing the coating with enhanced stability by abundant interactions among each coating component (e.g. boric acid ester bond formation, weak intermolecular cross-linking, π-π interactions and H-bonding). Moreover, rapamycin and atorvastatin calcium were selected as drug candidates and loaded into micelles, following with drug releasing behavior study. It was found that the LBL coating maintained a linear growth mode up to 30 cycles, giving a favourable tunability of coating construction and drug loading. The coating could also support sustained release of payloads, and provide wild tissue response. With the systematic in vitro and in vivo study, such catechol-phenylboronic acid enhanced LBL coating with drug loading would also address enhanced anti-platelet adhesion/activation and direct cell fate of endothelial cells and smooth muscle cells via tuning the coating cycles and loaded drugs. With the modular assembling, such coating indicated potential in achieving enhanced re-endothelialization for vascular implants.