Preparation And Drug Delivery Behavior Of Mineralized Collagen/PIGA-PEG-PLGA Copolymer Coatings

For orthopedic implants, both excellent biological performances and drug delivery capacity are required, if successful implantation with high quality is to be achieved. Mineralized collagen coating, which composed of calcium phosphate and collagen, is considered to be an ideal alternative for surface modification of metallic implants. For thin bioactive coatings on the metallic implant, however, the drug-loading capacity and sustained release ability remain a challenge.In this work, we attempted to incorporate drug-loaded PLGA-PEG-PLGA micelles into the thin coatings with appropriate microstructure, aiming to improve the drug-e luting capability while retaining the excellent bioactivity of mineralized collagen coatings. Since vancomycin hydrochloride (VH) is commonly used for preventing bacterial infection, it was used as a model drug.Mineralized collagen coatings were prepared by electrochemical deposition (ECD), and the key factors of controllable preparation of the coatings were proposed on the basis of ECD mechanism. It could be concluded that the regulation of the pH gradient near the cathode and the isoelectric point of collagen was the key to controllable preparation. It was demonstrated the drug delivery behaviors of mineralized collagen coatings with different microstructures also differed, but that the differences were not significant. Thus, it is not efficient to improve the drug delivery capability through the adjustment of coating microstructure.PLGA-PEG-PLGA micelles with size of300-600nm and15-30nm were prepared by direct dissolution method and solvent-dialysis method respectively. Since PLGA-PEG-PLGA micelles could not attach tightly to the Ti substrates and calcium phosphate crystals directly but could adhere closely to the collagen fibrils, the bare collagen fibrils on the coating surface could serve as the adhering sites for PLGA-PEG-PLGA micelles. It was observed that VH-loaded PLGA-PEG-PLGA micelles were successfully immobilized on the porous coatings. Immersion test in PBS also indicated good adhesion strength of the micelles to the mineralized collagen coatings.The in-vitro release profiles showed that burst release was moderated to some extent and that the release duration was prolonged after micelle modification, compared to mineralized collagen coatings alone. It was also found that the preparation methods of micelles, micelle concentrations, drug-loading ways and the microstructure of mineralized collagen all have effects on the drug delivery behaviors of the coatings. Modified Higuchi equation was introduced to analyze experimental release data. Combined with the characterization of the coatings and micelles, the modified Higuchi model explained how the micelles optimized the drug delivery behaviors. Specifically, the PLGA-PEG-PLGA micelles immobilized on the coatings could ameliorate the drug distribution, and retard the drug diffusion through reducing the porosity of the coatings and increasing the tortuosity at the same time.The antimicrobial activity test by S. aureus culture showed that drug-loading coatings modified by PLGA-PEG-PLGA micelles had good antibacterial activity. And the cytocompability assay by MC3T3-E1pre-osteoblast culture demonstrated that the whole coatings could greatly enhanced cell activity.Thus, the porous mineralized collagen coating on Ti substrates immobilized with drug-loaded PLGA-PEG-PLGA micelles could be an effective implant model for bone repair.