The Fabrication And Functions Of PH-responsive Local Drug Delivery Ti-based Implants

Osteosarcoma is a primary malignant tumor of bone that often occurs in adolescents.Clinical treatment options for osteosarcoma are mainly preoperative and postoperative chemotherapy combined with surgical resection,however,chemotherapy can lead to serious side effects.After surgical resection of osteosarcoma,titanium(Ti)-based implants are commonly used for tissue repair and bone reconstruction at the resected site.However,most Ti-based implants show good biocompatibility and mechanical properties,but they are bio-inert materials that provide only mechanical support and lack bioactivity and biofunctionality.Based on the above-mentioned problems,in this thesis,titania nanotube(TNT)arrays were prepared on the surface of pure titanium by electrochemical anodic oxidation technique,and the nanotubes were modified with polydopamine(PDA)and loaded with Doxorubicin Hydrochloride(DOX)using a cyclic piggyback method.The samples were characterized using Fourier Transform Infrared spectroscopy,scanning electron microscopy,and water contact angle;drug release behavior was investigated and the release mechanism was studied.It was shown that the sample surfaces after anodic oxidation presents the best hydrophilicity(p < 0.05)and weakened after modification with polydopamine,but still hydrophilic compared to the pure Ti surface.The sample after drug loading shows significant nanotube structures with significantly enhanced hydrophilicity(p < 0.05).The drug release results showed that the drug release of the TNT-PDA-DOX group shows pH-responsive compared to the TNT-DOX group,presenting a smaller cumulative percentage and release rate at neutral pH,and a gradual increase with decreasing pH.The data fitting revealed that the drug release kinetics of TNT-DOX followed the first-order model,and TNT-PDA-DOX followed the Fickian diffusion mechanism during the initial phase of drug release(first 6 h)and the first-order model during the slow release phase of drug(24 h-120 h).The biocompatibility of the samples was investigated by cell activity assay,live/dead staining,and morphological observation under the direct contact model between the samples and MC3T3 cells.The results showed that the TNT-PDA group present the best biocompatibility(p < 0.05),and the TNT-PDA-DOX group showed significantly higher biocompatibility(p < 0.05)compared to the TNT-DOX group.The anti-tumor ability of the samples was investigated by cell activity assay,live/dead staining,and morphological observation under indirect and direct contact models between the samples and MG-63 cells.The results showed that the tumorkilling ability of TNT-PDA-DOX under the indirect contact model show gradually increased with the decrease of pH of the culture medium.The co-localization experiments between the nucleus and DOX showed that the DOX release from TNTPDA-DOX gradually increased as the pH decreased,resulting in a progressively higher amount of DOX uptake by the cells.The TNT-PDA-DOX and TNT-DOX exhibit low tumor cell activity(p < 0.05)and show no significant different under the direct contact model.It indicates that TNT-PDA-DOX can respond to the acidic environment of tumor and release a large amount of drugs to achieve tumor-killing effect.