Construction Coating And Stimulate-Release Systems Based On Porous TiO₂ Materials

With the development of biomaterials and medical science,many biomedical implants have emerged（e.g.,hip replacements,dental implants,etc.）that require subsequent drug therapy regiments to aid in recovery.Because of the exceptional mechanical properties,titanium-based metals have been wildly used for repairing or replacing damaged hard tissues such as bones and teeth.However,these metallic implants are vulnerable to bacterial infections due to the easy of formation of highly structured microbial biofilms on the surface,which often induces the failure of orthopedic implant surgeries.Furthermore,the current therapy for these infections involves administering drugs orally or intravenously to distribute drugs throughout the entire body,which is significantly more than what is needed for the infection site.Furthermore,overuse of drugs can possibly reduce the natural immune system and also induce drug resistance.Local drug delivery can minimize these problems by reducing the unnecessary side effects by locally releasing proper amounts of drugs that are needed to achieve the same effect.The common strategy is to develop a local drug delivery system on the surface of metallic implants to control drug release.Compared with traditional systematic administration,the specific controlled release systems can offer many distinctive advantages by regulating the loading and release behaviors via thermal,p H,light,or magnetic stimuli.As we know,the local bacterial infection on the implantation site can reduce the local pH value from neutral to 6.0 or lower due to the formation of a large amount of H⁺.Accordingly,the pH-responsive drug loading systems can smartly adjust the amount of drugs that are released into the specific place with a low number of side effects.Therefore,in this thesis,a much more intelligent system holding not only better antibacterial property but also a little cytotoxictity are explored.The contents are as below:1:Controlled release and biocompatibility of polymer/titania nanotube array system on titanium implants:In this part,a hybrid surface system composed of biodegradable poly（lactic-co-glycolic acid）（PLGA）and titania nanotubes（TNTs）has been successfully constructed on Ti implants with the aim of preventing bacterial infection through long-term drug release.By varying the size of the TNTs and the thickness of the polymer film,the drug release profile can be tuned to achieve the optimal therapeutic action throughout the treatment time.The size of TNTs plays a dominant role in the drug loading dose of TNTs/PLGA hybrid coatings.In this work,TNTs with an average size of 80 nm can achieve the largest loading dose.Depending on the polymer thickness,significant improvement in the drug release characteristics is attained,etc.reduced burst release and extend release time.In addition,the PLGA layers may favor the proliferation and osteogenesis of MC3T3-E1 mouse cells at an earlier stage.Therefore,this TNT/PLGA hybrid surface system can be employed as an effective bioplatform for improving both self-antibacterial performance and biocompatibility of Ti-based biomaterials.2:pH-Triggered Drug Release and biocompatibility of polymer/titania nanotube array system on titanium implants:Based on the previous chapter,NaHCO₃ was loaded into TNTs with Ibu.And 3 layers of PLGA were coated onto the samples.The release behavior was tested at different pH of PBS.Furthermore,the cytoactivity of samples is explored through in vitro test.3:Metal Ion Coordination Polymer-Capped pH-Triggered Drug Release System on Titania Nanotubes for Enhancing Self-antibacterial Capability of Ti implants:In this chapter a novel hybrid system with a highly efficient,bio-responsive and controlled release of antibacterial activity via the metal ion coordination polymer on TNTs.These hybrid systems exhibited a self-defense behavior that is triggered by the change of the ambient environment acidity due to bacterial infection with gram-positive bacteria Staphylococcus aureus（S.aureus）and gram-negative bacteria Escherichia coli（E.coli）.The antibacterial agents,including antibiotics and nanosilver particles,can be loaded into TNTs and then sealed with coordination polymers（CPs）through the attachment of metallic ions such as Zn²⁺or Ag⁺.The zinc and silver ions work as intermediate coordination bonds,and they are sensitive to the change in H⁺.Due to the strong bonding of CPs,the amount of released antimicrobial agents is maintained at a non-significant level when pH is maintained at 7.4.However,the coordination bond of the capped CPs was triggered to open to release antibacterial agents from TNTs once the environment becomes acidic.The release rate gradually increased as the pH value further decreased.Subsequently,the antibacterial efficiency of the hybrid system is accelerated as the local microenvironment becomes more acidic during bacterial infection.In addition,the metal ions that are used for intermediate bond bridging are also favorable for specific biological functions.For example,Zn²⁺can promote the proliferation of osteoblastic cells,while Ag⁺can further enhance the antibacterial capability.In conclusion,this smart surface coating system not only demonstrates excellent self-antibacterial properties and biocompatibility but also formulates a controllable delivery system for the long-lasting treatment of biomaterial-related bacterial infections.