Titania nanotube (TNTs) arrays engineered by simple and scalable electrochemical anodization process have been extensively explored as a new nanoengineering approach to address the limitations of systemic drug administration. Due to their outstanding properties and excellent biocompatibility, TNTs arrays have been used to develop new drug-releasing implants (DRI) for emerging therapies based on localized drug delivery (DD). This review highlights the concepts of DRI based on TNTs with a focus on recent progress in their development and future perspectives towards advanced medical therapies. Recent progress in new strategies for controlling drug release from TNTs arrays aimed at designing TNTs-based DRI with optimized performances, including extended drug release and zero-order release kinetics and remotely activated release are described. Furthermore, significant progress in biocompatibility studies on TNTs and their outstanding properties to promote hydroxyapatite and bone cells growths and to differentiate stem cells are highlighted. Examples of ex vivo and in vivo studies of drug-loaded TNTs are shown to confirm the practical and potential applicability of TNTs-based DRI for clinical studies. Finally, selected examples of preliminary clinical applications of TNTs for bone therapy and orthopedic implants, cardiovascular stents, dentistry and cancer therapy are presented. As current studies have demonstrated, TNTs are a remarkable material that could potentially revolutionize localized DD therapies, especially in areas of orthopedics and localized chemotherapy. However, more extensive ex vivo and in vivo studies should be carried out before TNTs-based DRI could become a feasible technology for real-life clinical applications. This will imply the implementation of different approaches to overcome some technical and commercial challenges.

Titanium (Ti) and its alloys offer favorable biocompatibility, mechanical properties and corrosion resistance, which makes them an ideal material choice for dental implants. However, the long-term success of Ti-based dental implants may be challenged due to implant-related infections and inadequate osseointegration. With the development of nanotechnology, nanoscale modifications and the application of nanomaterials have become key areas of focus for research on dental implants. Surface modifications and the use of various coatings, as well as the development of the controlled release of antibiotics or proteins, have improved the osseointegration and soft-tissue integration of dental implants, as well as their antibacterial and immunomodulatory functions. This review introduces recent nano-engineering technologies and materials used in topographical modifications and surface coatings of Ti-based dental implants. These advances are discussed and detailed, including an evaluation of the evidence of their biocompatibility, toxicity, antimicrobial activities and in-vivo performances. The comparison between these attempts at nano-engineering reveals that there are still research gaps that must be addressed towards their clinical translation. For instance, customized three-dimensional printing technology and stimuli-responsive, multi-functional and time-programmable implant surfaces holds great promise to advance this field. Furthermore, long-term in vivo studies under physiological conditions are required to ensure the clinical application of nanomaterial-modified dental implants.

Here, we report on the development of advanced biopolymer-coated drug-releasing implants based on titanium (Ti) featuring titania nanotubes (TNTs) on its surface. These TNT arrays were fabricated on the Ti surface by electrochemical anodization, followed by the loading and release of a model antibiotic drug, gentamicin. The osteoblastic adhesion and antibacterial properties of these TNT-Ti samples are significantly improved by loading antibacterial payloads inside the nanotubes and modifying their surface with two biopolymer coatings (PLGA and chitosan). The improved osteoblast adhesion and antibacterial properties of these drug-releasing TNT-Ti samples are confirmed by the adhesion and proliferation studies of osteoblasts and model Gram-positive bacteria (Staphylococcus epidermidis). The adhesion of these cells on TNT-Ti samples is monitored by fluorescence and scanning electron microscopies. Results reveal the ability of these biopolymer-coated drug-releasing TNT-Ti substrates to promote osteoblast adhesion and proliferation, while effectively preventing bacterial colonization by impeding their proliferation and biofilm formation. The proposed approach could overcome inherent problems associated with bacterial infections on Ti-based implants, simultaneously enabling the development of orthopedic implants with enhanced and synergistic antibacterial functionalities and bone cell promotion.