TiO2 Used for Better Performance as Orthopedic Implants: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Catherine Yang and Version 1 by Zhou LI.

Titanium dioxide (TiO2)  is the native oxide layer of Ti which has good biocompatibility as well as enriched physical, chemical, electronic, and photocatalytic properties. The formed nanostructures during fabrication and the enriched properties of TiO2 have enabled various functionalization methods to combat the micro-organisms and enhance the osteogenesis of Ti implants. 

  • TiO2
  • Ti implants
  • antibacterial properties
  • osteogenesis

1. Important Facts about Orthopedic Implant

1.1. Implant Failure

The success of bone surgical operations mainly depends on the quality of implantable biomaterials. Implant success is mainly halted by the infections caused by post-operative complications. Certain factors may lead to bacterial infections or even failure, including extensive damage to local tissues, improper fixation, smoking, diabetes, chemotherapy, irradiation, and inappropriate surgical techniques [10][1]. The implants may get an infection from surgery equipment, medical staff, room atmosphere, or bacteria in the patient’s blood. The outcome of these microbial infections sometimes becomes grave, leading to a second surgery, amputation, or even death [11][2]. Implant infections are mostly initiated by Staphylococcus epidermidis (S. epidermidis), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Enterobacteriaceae [12][3].
Implant failure may occur at early or late stage [13][4]. Lack of osseointegration may lead to early implant failure, whereas in late implant failures, osseointegration works well at the beginning but decreases later due to disease and biochemical overload [14][5]. Researchers have identified various reasons for implant failures, which include infectious and physical damage [15][6]. Implant failures can be minimized by maintaining hygienic measures, caring for physical damage, and regular review of implants.
Progressive bone loss occurs due to inflammatory lesions in the soft tissues associated with the implants [13][4] and peri-implant disease [16][7]. Poor hygienic measures, unmanaged diseases such as diabetes, and the use of corticosteroids in immune-compromised individuals may all lead to that situation [17,18][8][9]. Despite taking all necessary hygienic measures, bacterial infections may still occur. Studies have suggested that joint infections may take place in 1% of primary and 3–7% of multiple surgeries [19,20][10][11]. Patients with multiple surgeries have a higher risk of mortality and infection [19][10]. Implant infections and failures are a large economic burden on the health system. In the US, it costs more than $8.6 billion annually [19,21][10][12].

1.2. Fundamental Requirements of Orthopedic Implants

Bone is naturally composed of organic, inorganic, and collagen fibrils. The nano-hierarchical structures give shape and mechanical strength to bones [22][13]. The structures include small molecular amino acids forming tropocollagen helixes and nanoscale collagen fibers forming a microporous network of bones. There is a crucial interaction between surface characteristics and the extracellular matrix for osteointegration [23][14]. Bone mesenchymal stem cells (BMSC) in the bone marrow are known to typically respond to metallic implants with the production of soft tissue rather than bone, which causes implants to fail [24,25][15][16]. Guiding stem cell differentiation to a desired specific line on the surface of the material is a key factor in the success of implants [26,27][17][18]. Osteoblasts are mature bone cells, whereas osteoprogenitor cells are pluripotent cells having the capacity to differentiate into different kinds of cells. Osteoblasts and osteoprogenitor cells are in direct contact with the implants.
For better outcomes, the hierarchical structures of the bone must be simulated by the implant with surface nanostructures to support bone tissue regeneration. Apart from the surface nanostructures, other modifications, including nanoparticles, may help further. For example, bismuth oxide (Bi2O3) has features including electrochemical stability, high biocompatibility, and a medium band gap [28,29][19][20]. The contact of Bi2O3 nanoparticles and TiO2 nanocones resulted in a heterojunction that formed a built-in electric field and promoted the osteogenesis of BMSC on the basis of TiO2 nanostructures [30][21].
 
2. Functionalization Approaches of TiO

2. Functionalization Approaches of TiO

2

 for Better Antibacterial and Osteogenesis Property

2.1. Topological Influence of the TiO2 Nanostructures

Topological modification is among the proposed methods to achieve surface functionalization. Studies have shown that surface nanostructure and topography may affect the migration, elongation, proliferation, and differentiation of stem cells [33,34,35][22][23][24]. In fact, cells and tissues in vivo will experience many topographic features ranging from nanoscale to microscale [36][25]. Thus, building a surface nanostructure on implants is an important research direction in the fields of artificial bones, joints, and dental implants [37,38,39][26][27][28]. The regulation of cell fate by surface topography is carried out by direct contact with adhering cells.
It has been widely accepted to form TiO2 nanotubes on Ti surfaces by doing anode oxidation, and the annealing after anodization enhances the nanotube’s roughness and osseointegration capability [40,41][29][30]. Cell behavior is affected by the diameter of TiO2 nanotubes [40][29]. For instance, small nanotubes (30 nm in diameter) have been shown to promote BMSC adherence without significant differentiation, while larger nanotubes (70–100 nm in diameter) cause a dramatic lengthening of stem cells, which induces cytoskeletal stress and selective differentiation into osteoblast-like cells [42][31]. A diameter of 70 nm is the optimum size of TiO2 nanotubes for osteogenic differentiation of stem cells derived from human adiposity [43][32]. The diameters of TiO2 nanotubes are crucial for surface roughness and hydrophilicity. Several studies have shown that increasing diameter can increase antibacterial characteristics [44,45][33][34]. Ercan et al. found that nanotubes with a diameter of 80 nm had more antibacterial properties than the 30 nm diameter nanotubes against various strains of S. aureus due to higher hydrophobicity [46][35]. Other factors apart from the diameter, including the length, the gap between walls, and crystal forms, also influence the TiO2 nanotubes. Nano-engineered Ti prepared from hydrothermal etching has also been reported to be effective against gram-negative bacteria, E. coli [47][36].
 
TiO2 nanorod, another TiO2 nanostructure, also significantly influences the BMSC behavior [43][32]. The TiO2 nanorod array surface is very effective in regulating the differentiation of BMSC towards osteoblasts. In another study, TiO2 ceramics were synthesized and TiO2 nanorods were used to compare the BMSC cellular adhesion and self-renewal characteristics when commercial culture plates were used as the control group [48][37]. All samples demonstrated good biocompatibility from day 2 to day 8, suggesting that TiO2 ceramic promotes cell adhesion, renewal, and cellular morphology).
Increasing the average surface roughness of the implant promotes osteointegration and is another topology-based surface modification [49][38]. The surface roughness enhances protein adsorption and osteoblastic functions [50][39]. The inorganic coating may include calcium phosphate/hydroxyapatite and certain peptides [51][40]. However, a thick layer of calcium phosphate coating has poor stability [52][41]. To address this issue, biomimetic strategies were devised, which have shown good versatility [49,53][38][42]. This coating has great osteoconductive potential in vivo [54][43].

2.2. Drug Loading and Release Based on the TiO

2.2. Drug Loading and Release Based on the TiO

2 Nanostructures

Nanostructures

Antibiotics are very effective at killing bacteria, but antibiotics taken by oral or muscular injection have very low efficiency in treating infections in the bone. Localized drug release from the implant surface can solve the problem. TiO2 nanostructures such as nanotubes and nanopores are highly facilitated to do drug-loading [49,50][38][39]. TiO2 nanotubes are especially favored because of their larger surface area and one-end open feature [55][44]. The drug delivery of the nanotubes is significantly affected by the fabrication conditions. It is also found that drug release was promoted by increasing the dimensions (length, width, and diameter) of nanotubes [56][45]. Loading into the nanotubes with infection-reducing drugs, such as penicillin and streptomycin, largely improves the performance of titanium implants [57,58][46][47].
By increasing the dimensions of the nanotubes, drug release was promoted, but drug loss also increased during the rinsing process. To overcome this problem, periodic structures in the nanotubes are prevented, which demonstrated a significant improvement in the drug release control; the periodic structures largely reduced drug burst release from 77% to 50% and extended overall release from 4 days to more than 17 days [39][28].

2.3. Element Incorporation

Apart from biotics, the antibacterial property can also be promoted by introducing antibacterial ions, such as silver (Ag), zinc (Zn), and magnesium (Mg) [62,63,64,65,66][48][49][50][51][52]. Jia et al. reported a method to incorporate Ag nanoparticles into TiO2 microporous coatings using polydopamine [62][48]. A sustained release of Ag+ ions for up to 28 days was observed, which endowed the Ti implant with long-term antibacterial ability. An additional trap-killing of the bacteria was enabled with these Ag nanoparticles. Negatively charged bacteria were attracted toward the positively charged Ag nanoparticles and killed with more efficiency. More Ag doping to TiO2 for better antibacterial properties can be found in the literature [67,68,69][53][54][55].
Zn is an important trace element in the human body, and it has a pivotal role in DNA synthesis, enzymatic activities, biomineralization, hormonal activities, and antibacterial characteristics [70,71,72,73,74][56][57][58][59][60]. Zn doping in TiO2-based biomaterial has also been found to possess excellent antibacterial activities and better cell-material interactions [75,76][61][62]. The bacterial killing was due to the penetration of Zn2+ in the bacterial surface membranes [77][63].
Mg is a microelement in the body and contributes to numerous cellular functions including enzymatic reactions, proteins, and nucleic acid synthesis; it is also effective in reducing inflammation and bone loss [79,80][64][65]. The incorporation of Mg can inhibit bacterial infection and osteolysis. Yang Y et al. designed a surface with Mg incorporated into the TiO2 nanotubes [78][66]. The surface demonstrated remarkable antibacterial properties, enhanced cytocompatibility, and inhibited osteoclast genesis, both in vitro and in vivo. The nanostructures and alkaline microenvironment during degradation were responsible for the antimicrobial ability. The continuous release of Mg2+ suppressed the osteolysis via down-regulation of NF-κB/NFATc1 signaling. Mg doping has multiple therapeutic effects; however, an alkaline environment may pose a serious challenge in clinical use. Controlled release of Mg is the possible solution but needs further exploration [81][67]. Many other studies support that Mg incorporation can enhance the antibacterial and osteogenesis property of the implants [81,82][67][68].

2.4. Electron Transfer

In recent years, an antibacterial theory based on the electron transfer between the material surface and the microbes has been proposed. Electron transfer is a common event in the photochemical modulation of materials, as well as a fundamental event for the energy generation of organisms [83][69]. A group of microbes can do extracellular electron transfer spontaneously by transferring the electron outside the cells to environmental minerals [84][70]. However, using the electron transfer approach to inhibit implant infection is a quite new topic [85][71].
Vecitis et al. found that the antibacterial properties of single-arm carbon nanotubes are closely related to their electronic state. With the same diameter and length, metallic carbon nanotubes can cause severe deformation and collapse of the bacterial cells, while those in a semi-conductive state have no antibacterial properties [86][72]. Faria et al. found that the composite structure of Ag nanoparticles and graphene lamellae has a strong bactericidal ability, but graphene lamellae itself does not, suggesting that the electronic interactions between the substrate and the modified materials have a dominant impact on the antibacterial property [87][73].
TiO2 also has complex interactions with the bacteria and osteoblasts via electron transfer. TiO2 is a semiconductor, and biological cells can also be regarded as semiconductors [88][74]. Once contacted, they form heterojunctions, which may involve electron transfer. Therefore, functionalization based on the electron transfer property also influences the performance of TiO2 as an orthopedic implant. Au and Ag nanoparticles or graphene sheets deposited on the TiO2 surface can endow TiO2 with antibacterial properties [88,89,90,91,92,93][74][75][76][77][78][79]. On the Ag@TiO2 surface, electrons were stored on the Ag nanoparticles, and induced valence-band hole (h+) accumulation, which caused cytosolic content leakage of the bacteria [89][75]. On the Au@TiO2 surface, electron transfer was due to the plasmon effect of Au nanoparticles, which captured the electrons in the respiratory chain on the living bacterial cell membrane and transferred them to the TiO2 substrate. Au@TiO2 formed the Schottky barrier, which prevented the return of electrons, causing continued electron loss in the bacteria until death [91,93][77][79]. Similarly, graphene coating resulted in a large increase in the electrical conductivity of TiO2 because of the combination of the unpaired π electrons of graphene and the Ti atoms [94][80]. The enhanced electron transfer from the bacterial cell membrane to the graphene-TiO2 interface leads to bacterial death.
Electron transfer also works for osteogenesis. Zhou et al. fabricated a SnO2–TiO2 heterojunction and hierarchical structure on the surface of the Ti implant [95][81]. The electron transfer among the hierarchical Schottky barrier significantly improved the osteogenic function of the cells around the implant both in vitro and in vivo. In another work, they constructed a layered double hydroxide (LDHs)–TiO2 heterojunction, which promoted the transfer of holes in materials to the physiological environment, enhancing the antibacterial effect of the implant [96][82]. Ning et al. generated a microscale electrostatic field (MEF) by doing patterned NT (rutile) and IT (anatase) surface modifications on Ti [97][83]. The electron transfer between NT and IT zones formed a sustained built-in MEF, which polarized the BMSC and activated the expression of osteogenic genes. The MEF greatly promoted bone regeneration around the implant.
Apart from TiO2, the Ti surface can also make electron transfer-based interactions with the bacteria. In a study by Wang et al., Ag was implanted on the Ti surface using plasma technology, and this modification changed the Ti surface from non-antibacterial to antibacterial [93][79]. The bacteria-killing was not due to Ag+ ion release, but due to the micro galvanic reaction at the nano interface between Ag nanoparticles and Ti substrate. The reaction disturbed the process of electron transfer in the bacteria respiratory chain and produced a large number of reactive oxygen species (ROS) in the bacterial cells, resulting in their death.

2.5. Electrical Functionalization

Based on the electron transfer mechanism of the above studies, researchers have further developed an innovative method to make the TiO2 surface obtain antibacterial properties through electrical tuning. In the beginning, it was found that an alternating current (AC) of about ±2 μA applied to the ZnO nanowires in a physiological solution could significantly improve the antibacterial property of ZnO after the current was removed. The “sustained bacteria sterilization” was different from the “instant bacteria sterilization” because the latter was due to electroporation when AC was applied to the nanowires, but the former was due to surface functionalization by the electrical tuning [98][84]. After that, a 2 V low-voltage direct current (DC) power supply was used to conduct electrical treatment on the Ti plate with a TiO2 layer in the culture medium for 20 min. This DC tuning also changed the TiO2 surface from non-antibacterial to highly antibacterial [99][85]. After the electric tuning, TiO2 gained a strong ability to kill various bacteria and showed strong inhibition of biofilm formation. Meanwhile, the DC-tuned TiO2 surface had no negative effect on the osteoblast. The adhesion and proliferation of the cells were found to be as effective as those on the control TiO2 surface.

References

  1. Chevalier, J.; Gremillard, L. Ceramics for medical applications: A picture for the next 20 years. J. Eur. Ceram. Soc. 2009, 29, 1245–1255.
  2. Moriarty, T.F.; Schlegel, U.; Perren, S.; Richards, R.G. Infection in fracture fixation: Can we influence infection rates through implant design? J. Mater. Sci. Mater. Med. 2010, 21, 1031–1035.
  3. Gittens, R.A.; Scheideler, L.; Rupp, F.; Hyzy, S.L.; Geis-Gerstorfer, J.; Schwartz, Z.; Boyan, B.D. A review on the wettability of dental implant surfaces II: Biological and clinical aspects. Acta Biomater. 2014, 10, 2907–2918.
  4. Lindhe, J.; Meyle, J.; Group D of the European Workshop on Periodontology. Peri-implant diseases: Consensus report of the sixth European workshop on periodontology. J. Clin. Periodontol. 2008, 35, 282–285.
  5. Chen, S.; Darby, I. Dental implants: Maintenance, care and treatment of peri-implant infection. Aust. Dent. J. 2003, 48, 212–220.
  6. Periodontology, A.A. of Parameter on placement and management of the dental implant. J. Periodontol. 2000, 71, 870–872.
  7. Tonetti, M.S. Risk factors for osseodisintegration. Periodontol. 2000 1998, 17, 55–62.
  8. Fujimoto, T.; Niimi, A.; Sawai, T.; Ueda, M. Effects of steroid-induced osteoporosis on osseointegration of titanium implants. Int. J. Oral Maxillofac. Implant. 1998, 13, 183–189.
  9. Farzad, P.; Andersson, L.; Nyberg, J. Dental implant treatment in diabetic patients. Implant Dent. 2002, 11, 262–267.
  10. Halpern, M.; Kurtz, S.; Lau, E.; Mowat, F.; Ong, K. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J. Bone Surg. 2007, 89, 780–785.
  11. Lentino, J.R. Prosthetic joint infections: Bane of orthopedists, challenge for infectious disease specialists. Clin. Infect. Dis. 2003, 36, 1157–1161.
  12. Campoccia, D.; Montanaro, L.; Arciola, C.R. The significance of infection related to orthopedic devices and issues of antibiotic resistance. Biomaterials 2006, 27, 2331–2339.
  13. Bosco, R.; Van Den Beucken, J.; Leeuwenburgh, S.; Jansen, J. Surface engineering for bone implants: A trend from passive to active surfaces. Coatings 2012, 2, 95–119.
  14. Brammer, K.S.; Frandsen, C.J.; Jin, S. TiO2 nanotubes for bone regeneration. Trends Biotechnol. 2012, 30, 315–322.
  15. Dalby, M.J.; Gadegaard, N.; Tare, R.; Andar, A.; Riehle, M.O.; Herzyk, P.; Wilkinson, C.D.W.; Oreffo, R.O.C. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat. Mater. 2007, 6, 997–1003.
  16. Ratner, B.D.; Bryant, S.J. Biomaterials: Where we have been and where we are going. Annu. Rev. Biomed. Eng. 2004, 6, 41–75.
  17. Lutolf, M.P.; Gilbert, P.M.; Blau, H.M. Designing materials to direct stem-cell fate. Nature 2009, 462, 433–441.
  18. Chrzanowski, W.; Lee, J.H.; Kondyurin, A.; Lord, M.S.; Jang, J.; Kim, H.; Bilek, M.M.M. Nano-Bio-Chemical Braille for Cells: The Regulation of Stem Cell Responses using Bi-Functional Surfaces. Adv. Funct. Mater. 2015, 25, 193–205.
  19. Huang, H.; He, L.; Zhou, W.; Qu, G.; Wang, J.; Yang, N.; Gao, J.; Chen, T.; Chu, P.K.; Yu, X.-F. Stable black phosphorus/Bi2O3 heterostructures for synergistic cancer radiotherapy. Biomaterials 2018, 171, 12–22.
  20. Lu, H.; Hao, Q.; Chen, T.; Zhang, L.; Chen, D.; Ma, C.; Yao, W.; Zhu, Y. A high-performance Bi2O3/Bi2SiO5 pn heterojunction photocatalyst induced by phase transition of Bi2O3. Appl. Catal. B Environ. 2018, 237, 59–67.
  21. Huang, X.; Xing, J.; Wang, Z.; Han, J.; Wang, R.; Li, C.; Xiao, C.; Lu, F.; Zhai, J.; Zhou, Z. 0D/1D Heterojunction Implant with Electro-Mechanobiological Coupling Cues Promotes Osteogenesis. Adv. Funct. Mater. 2021, 31, 2106249.
  22. Calabrese, G.; Franco, D.; Petralia, S.; Monforte, F.; Condorelli, G.G.; Squarzoni, S.; Traina, F.; Conoci, S. Dual-Functional Nano-Functionalized Titanium Scaffolds to Inhibit Bacterial Growth and Enhance Osteointegration. Nanomaterials 2021, 11, 2634.
  23. Shao, Y.; Fu, J. Integrated micro/nanoengineered functional biomaterials for cell mechanics and mechanobiology: A materials perspective. Adv. Mater. 2014, 26, 1494–1533.
  24. Kim, D.-H.; Provenzano, P.P.; Smith, C.L.; Levchenko, A. Matrix nanotopography as a regulator of cell function. J. Cell Biol. 2012, 197, 351–360.
  25. Dvir, T.; Timko, B.P.; Kohane, D.S.; Langer, R. Nanotechnological strategies for engineering complex tissues. Nat. Nanotechnology 2011, 6, 13–22.
  26. Dalby, M.J.; Gadegaard, N.; Oreffo, R.O.C. Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate. Nat. Mater. 2014, 13, 558–569.
  27. Yao, X.; Peng, R.; Ding, J. Cell–material interactions revealed via material techniques of surface patterning. Adv. Mater. 2013, 25, 5257–5286.
  28. Li, Y.; Yang, Y.; Li, R.; Tang, X.; Guo, D.; Qing, Y.; Qin, Y. Enhanced antibacterial properties of orthopedic implants by titanium nanotube surface modification: A review of current techniques. Int. J. Nanomedicine 2019, 14, 7217–7236.
  29. Zhao, L.; Liu, L.; Wu, Z.; Zhang, Y.; Chu, P.K. Effects of micropitted/nanotubular titania topographies on bone mesenchymal stem cell osteogenic differentiation. Biomaterials 2012, 33, 2629–2641.
  30. Descamps, S.; Awitor, K.O.; Raspal, V.; Johnson, M.B.; Bokalawela, R.S.P.; Larson, P.R.; Doiron, C.F. Mechanical properties of nanotextured titanium orthopedic screws for clinical applications. J. Med. Devices 2013, 7, 021005.
  31. Oh, S.; Brammer, K.S.; Li, Y.S.J.; Teng, D.; Engler, A.J.; Chien, S.; Jin, S. Stem cell fate dictated solely by altered nanotube dimension. Proc. Natl. Acad. Sci. USA 2009, 106, 2130–2135.
  32. Lv, L.; Liu, Y.; Zhang, P.; Zhang, X.; Liu, J.; Chen, T.; Su, P.; Li, H.; Zhou, Y. The nanoscale geometry of TiO2 nanotubes influences the osteogenic differentiation of human adipose-derived stem cells by modulating H3K4 trimethylation. Biomaterials 2015, 39, 193–205.
  33. Li, Q.; Cai, T.; Huang, Y.; Xia, X.; Cole, S.P.C.; Cai, Y. A review of the structure, preparation, and application of NLCs, PNPs, and PLNs. Nanomaterials 2017, 7, 122.
  34. Peng, Z.; Ni, J.; Zheng, K.; Shen, Y.; Wang, X.; He, G.; Jin, S.; Tang, T. Dual effects and mechanism of TiO2 nanotube arrays in reducing bacterial colonization and enhancing C3H10T1/2 cell adhesion. Int. J. Nanomedicine 2013, 8, 3093.
  35. Ercan, B.; Taylor, E.; Alpaslan, E.; Webster, T.J. Diameter of titanium nanotubes influences anti-bacterial efficacy. Nanotechnology 2011, 22, 295102.
  36. Puckett, S.D.; Taylor, E.; Raimondo, T.; Webster, T.J. The relationship between the nanostructure of titanium surfaces and bacterial attachment. Biomaterials 2010, 31, 706–713.
  37. Qiu, J.; Li, J.; Wang, S.; Ma, B.; Zhang, S.; Guo, W.; Zhang, X.; Tang, W.; Sang, Y.; Liu, H. TiO2 nanorod array constructed nanotopography for regulation of mesenchymal stem cells fate and the realization of location-committed stem cell differentiation. Small 2016, 12, 1770–1778.
  38. Buensuceso, C.S.; Woodside, D.; Huff, J.L.; Plopper, G.E.; O’Toole, T.E. The WD protein Rack1 mediates protein kinase C and integrin-dependent cell migration. J. Cell Sci. 2001, 114, 1691–1698.
  39. Pegueroles, M.; Aparicio, C.; Bosio, M.; Engel, E.; Gil, F.J.; Planell, J.A.; Altankov, G. Spatial organization of osteoblast fibronectin matrix on titanium surfaces: Effects of roughness, chemical heterogeneity and surface energy. Acta Biomater. 2010, 6, 291–301.
  40. Geesink, R.G.T.; de Groot, K.; KLEIN, C.P.A.T. Chemical implant fixation using hydroxyl-apatite coatings: The development of a human total hip prosthesis for chemical fixation to bone using hydroxyl-apatite coatings on titanium substrates. Clin. Orthop. Relat. Res. 1987, 225, 147–170.
  41. Lee, J.J.; Rouhfar, L.; Beirne, O.R. Survival of hydroxyapatite-coated implants: A meta-analytic review. J. Oral Maxillofac. Surg. 2000, 58, 1372–1379.
  42. Dalby, M.J.; Hart, A.; Yarwood, S.J. The effect of the RACK1 signalling protein on the regulation of cell adhesion and cell contact guidance on nanometric grooves. Biomaterials 2008, 29, 282–289.
  43. Goodman, S.B.; Yao, Z.; Keeney, M.; Yang, F. The future of biologic coatings for orthopaedic implants. Biomaterials 2013, 34, 3174–3183.
  44. Xiao, X.; Yang, L.; Guo, M.; Pan, C.; Cai, Q.; Yao, S. Biocompatibility and in vitro antineoplastic drug-loaded trial of titania nanotubes prepared by anodic oxidation of a pure titanium. Sci. China Ser. B Chem. 2009, 52, 2161–2165.
  45. Yang, D.-J.; Kim, H.-G.; Cho, S.-J.; Choi, W.-Y. Thickness-conversion ratio from titanium to TiO2 nanotube fabricated by anodization method. Mater. Lett. 2008, 62, 775–779.
  46. Kulkarni, M.; Mazare, A.; Gongadze, E.; Perutkova, Š.; Kralj-Iglič, V.; Milošev, I.; Schmuki, P.; Iglič, A.; Mozetič, M. Titanium nanostructures for biomedical applications. Nanotechnology 2015, 26, 62002.
  47. Andersson, R.E.; Lukas, G.; Skullman, S.; Hugander, A. Local administration of antibiotics by gentamicin–collagen sponge does not improve wound healing or reduce recurrence rate after pilonidal excision with primary suture: A prospective randomized controlled trial. World J. Surg. 2010, 34, 3042–3046.
  48. Jia, Z.; Xiu, P.; Li, M.; Xu, X.; Shi, Y.; Cheng, Y.; Wei, S.; Zheng, Y.; Xi, T.; Cai, H. Bioinspired anchoring AgNPs onto micro-nanoporous TiO2 orthopedic coatings: Trap-killing of bacteria, surface-regulated osteoblast functions and host responses. Biomaterials 2016, 75, 203–222.
  49. Hwang, S.H.; Song, J.; Jung, Y.; Kweon, O.Y.; Song, H.; Jang, J. ElectrospunZnO/TiO2 composite nanofibers as a bactericidal agent. Chem. Commun. 2011, 47, 9164–9166.
  50. Paladini, F.; Pollini, M.; Sannino, A.; Ambrosio, L. Metal-based antibacterial substrates for biomedical applications. Biomacromolecules 2015, 16, 1873–1885.
  51. Chernousova, S.; Epple, M. Silver as antibacterial agent: Ion, nanoparticle, and metal. Angew. Chemie Int. Ed. 2013, 52, 1636–1653.
  52. Campoccia, D.; Montanaro, L.; Arciola, C.R. A review of the biomaterials technologies for infection-resistant surfaces. Biomaterials 2013, 34, 8533–8554.
  53. Zhang, Y.; Dong, C.; Yang, S.; Chiu, T.-W.; Wu, J.; Xiao, K.; Huang, Y.; Li, X. Enhanced silver loaded antibacterial titanium implant coating with novel hierarchical effect. J. Biomater. Appl. 2018, 32, 1289–1299.
  54. Hou, X.; Mao, D.; Ma, H.; Ai, Y.; Zhao, X.; Deng, J.; Li, D.; Liao, B. Antibacterial ability of Ag–TiO2 nanotubes prepared by ion implantation and anodic oxidation. Mater. Lett. 2015, 161, 309–312.
  55. Shanmuganathan, R.; MubarakAli, D.; Prabakar, D.; Muthukumar, H.; Thajuddin, N.; Kumar, S.S.; Pugazhendhi, A. An enhancement of antimicrobial efficacy of biogenic and ceftriaxone-conjugated silver nanoparticles: Green approach. Environ. Sci. Pollut. Res. 2018, 25, 10362–10370.
  56. Tang, Y.; Chappell, H.F.; Dove, M.T.; Reeder, R.J.; Lee, Y.J. Zinc incorporation into hydroxylapatite. Biomaterials 2009, 30, 2864–2872.
  57. Tas, A.C.; Bhaduri, S.B.; Jalota, S. Preparation of Zn-doped β-tricalcium phosphate (β-Ca3(PO4)2) bioceramics. Mater. Sci. Eng. C 2007, 27, 394–401.
  58. Lowe, N.M.; Fraser, W.D.; Jackson, M.J. Is there a potential therapeutic value of copper and zinc for osteoporosis? Proc. Nutr. Soc. 2002, 61, 181–185.
  59. Storrie, H.; Stupp, S.I. Cellular response to zinc-containing organoapatite: An in vitro study of proliferation, alkaline phosphatase activity and biomineralization. Biomaterials 2005, 26, 5492–5499.
  60. Applerot, G.; Lipovsky, A.; Dror, R.; Perkas, N.; Nitzan, Y.; Lubart, R.; Gedanken, A. Enhanced antibacterial activity of nanocrystalline ZnO due to increased ROS-mediated cell injury. Adv. Funct. Mater. 2009, 19, 842–852.
  61. Liu, X.; Zhao, X.; Li, B.; Cao, C.; Dong, Y.; Ding, C.; Chu, P.K. UV-irradiation-induced bioactivity on TiO2 coatings with nanostructural surface. Acta Biomater. 2008, 4, 544–552.
  62. de Assis, S.L.; Wolynec, S.; Costa, I. Corrosion characterization of titanium alloys by electrochemical techniques. Electrochim. Acta 2006, 51, 1815–1819.
  63. Díez-Pascual, A.M.; Diez-Vicente, A.L. Development of nanocomposites reinforced with carboxylated poly (ether ether ketone) grafted to zinc oxide with superior antibacterial properties. ACS Appl. Mater. Interfaces 2014, 6, 3729–3741.
  64. Steinmetz, O.; Hoch, S.; Avniel-Polak, S.; Gavish, K.; Eli-Berchoer, L.; Wilensky, A.; Nussbaum, G. CX3CR1hi Monocyte/Macrophages Support Bacterial Survival and Experimental Infection–Driven Bone Resorption. J. Infect. Dis. 2016, 213, 1505–1515.
  65. Wang, J.; Wu, X.; Duan, Y. Magnesium lithospermate B protects against lipopolysaccharide-induced bone loss by inhibiting RANKL/RANK pathway. Front. Pharmacol. 2018, 9, 64.
  66. Yang, Y.; Liu, L.; Luo, H.; Zhang, D.; Lei, S.; Zhou, K. Dual-purpose magnesium-incorporated titanium nanotubes for combating bacterial infection and ameliorating osteolysis to realize better osseointegration. ACS Biomater. Sci. Eng. 2019, 5, 5368–5383.
  67. Chopra, D.; Gulati, K.; Ivanovski, S. Understanding and optimizing the antibacterial functions of anodized nano-engineered titanium implants. Acta Biomater. 2021, 127, 80–101.
  68. Choe, H.J.; Kwon, S.-H.; Lee, J.-J. Tribological properties and thermal stability of TiAlCN coatings deposited by ICP-assisted sputtering. Surf. Coatings Technol. 2013, 228, 282–285.
  69. Harris, H.W.; El-Naggar, M.Y.; Bretschger, O.; Ward, M.J.; Romine, M.F.; Obraztsova, A.Y.; Nealson, K.H. Electrokinesis is a microbial behavior that requires extracellular electron transport. Proc. Natl. Acad. Sci. USA 2010, 107, 326–331.
  70. Shi, L.; Dong, H.; Reguera, G.; Beyenal, H.; Lu, A.; Liu, J.; Yu, H.-Q.; Fredrickson, J.K. Extracellular electron transfer mechanisms between microorganisms and minerals. Nat. Rev. Microbiol. 2016, 14, 651–662.
  71. Wang, D.; Tan, J.; Zhu, H.; Mei, Y.; Liu, X. Biomedical Implants with Charge-Transfer Monitoring and Regulating Abilities. Adv. Sci. 2021, 8, 1–38.
  72. Vecitis, C.D.; Zodrow, K.R.; Kang, S.; Elimelech, M. Electronic-structure-dependent bacterial cytotoxicity of single-walled carbon nanotubes. ACS Nano 2010, 4, 5471–5479.
  73. de Faria, A.F.; Martinez, D.S.T.; Meira, S.M.M.; de Moraes, A.C.M.; Brandelli, A.; Souza Filho, A.G.; Alves, O.L. Anti-adhesion and antibacterial activity of silver nanoparticles supported on graphene oxide sheets. Colloids Surf. B Biointerfaces 2014, 113, 115–124.
  74. Strahl, H.; Hamoen, L.W. Membrane potential is important for bacterial cell division. Proc. Natl. Acad. Sci. USA 2010, 107, 12281–12286.
  75. Cao, H.; Qiao, Y.; Liu, X.; Lu, T.; Cui, T.; Meng, F.; Chu, P.K. Electron storage mediated dark antibacterial action of bound silver nanoparticles: Smaller is not always better. Acta Biomater. 2013, 9, 5100–5110.
  76. Li, J.; Zhou, H.; Qian, S.; Liu, Z.; Feng, J.; Jin, P.; Liu, X. Plasmonic gold nanoparticles modified titania nanotubes for antibacterial application. Appl. Phys. Lett. 2014, 104, 261110.
  77. Wang, G.; Feng, H.; Gao, A.; Hao, Q.; Jin, W.; Peng, X.; Li, W.; Wu, G.; Chu, P.K. Extracellular electron transfer from aerobic bacteria to Au-loaded TiO2 semiconductor without light: A new bacteria-killing mechanism other than localized surface plasmon resonance or microbial fuel cells. ACS Appl. Mater. Interfaces 2016, 8, 24509–24516.
  78. Li, J.; Wang, G.; Zhu, H.; Zhang, M.; Zheng, X.; Di, Z.; Liu, X.; Wang, X. Antibacterial activity of large-area monolayer graphene film manipulated by charge transfer. Sci. Rep. 2014, 4, 1–8.
  79. Wang, G.; Jin, W.; Qasim, A.M.; Gao, A.; Peng, X.; Li, W.; Feng, H.; Chu, P.K. Antibacterial effects of titanium embedded with silver nanoparticles based on electron-transfer-induced reactive oxygen species. Biomaterials 2017, 124, 25–34.
  80. Yang, M.; Liu, H.; Qiu, C.; Iatsunskyi, I.; Coy, E.; Moya, S.; Wang, Z.; Wu, W.; Zhao, X.; Wang, G. Electron transfer correlated antibacterial activity of biocompatible graphene Nanosheets-TiO2 coatings. Carbon N. Y. 2020, 166, 350–360.
  81. Zhou, R.; Han, Y.; Cao, J.; Li, M.; Jin, G.; Du, Y.; Luo, H.; Yang, Y.; Zhang, L.; Su, B. Enhanced osseointegration of hierarchically structured Ti implant with electrically bioactive SnO2–TiO2 bilayered surface. ACS Appl. Mater. Interfaces 2018, 10, 30191–30200.
  82. Wang, D.; Li, Q.; Qiu, J.; Zhang, X.; Ge, N.; Liu, X. Corrosion motivated ROS generation helps endow titanium with broad-spectrum antibacterial abilities. Adv. Mater. Interfaces 2019, 6, 1900514.
  83. Ning, C.; Yu, P.; Zhu, Y.; Yao, M.; Zhu, X.; Wang, X.; Lin, Z.; Li, W.; Wang, S.; Tan, G. Built-in microscale electrostatic fields induced by anatase–rutile-phase transition in selective areas promote osteogenesis. NPG Asia Mater. 2016, 8, e243.
  84. Tian, J.; Feng, H.; Yan, L.; Yu, M.; Ouyang, H.; Li, H.; Jiang, W.; Jin, Y.; Zhu, G.; Li, Z. A self-powered sterilization system with both instant and sustainable anti-bacterial ability. Nano Energy 2017, 36, 241–249.
  85. Wang, G.; Feng, H.; Hu, L.; Jin, W.; Hao, Q.; Gao, A.; Peng, X.; Li, W.; Wong, K.-Y.; Wang, H. An antibacterial platform based on capacitive carbon-doped TiO2 nanotubes after direct or alternating current charging. Nat. Commun. 2018, 9, 1–12.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
ScholarVision Creations
Feedback