Antibacterial hydroxyapatite coatings on titanium dental implants

Abstract

Titanium and its alloys are often used as substrates for dental implants due to their excellent mechanical properties and good biocompatibility. However, their ability to bind to neighboring bone is limited due to the lack of biological activity. At the same time, they show poor antibacterial ability which can easily cause bacterial infection and chronic inflammation, eventually resulting in implant failure. The preparation of composite hydroxyapatite coatings with antibacterial ability can effectively figure out these concerns. In this review, the research status and development trends of antibacterial hydroxyapatite coatings constructed on titanium and its alloys are analyzed and reviewed. This review may provide valuable reference for the preparation and application of high-performance and multi-functional dental implant coatings in the future.

Key words： composite; dental implant; hydroxyapatite; titanium; antibacterial

Contents

Introduction

One-step method

Electrodeposition

Sol-gel method

Plasma spraying

Selective laser melting and magnetron sputtering

Multi-step method

Conclusion

Disclosure of potential conflicts of interests

Acknowledgements

References

1 Introduction

Titanium (Ti) presents light in weight, high in strength, moderate in hardness, low in thermal conductivity, and has good magnetic resonance compatibility. It can make stress transfer more in line with physiological patterns [1–3]. It is the most common metal material in orthopedic implants. Ti and its alloys as implants have lower elastic modulus that is closer to the human natural bone when compared with traditionally used stainless steels and Co–Cr alloys [4‒5].

With the development of medical research, the problems that limit the development of Ti-based materials have gradually emerged. The main problems are: (i) Ti is a biologically inert material, which cannot quickly form biological integration with surrounding tissues. It greatly reduces the initial stability of implantation and affects the success rate of surgery and postoperative healing rate [6‒7]. (ii) Ti-based metal itself lacks the ability of antibacterial and anti-infection [8‒9]. Therefore, it is easy to be infected by bacteria during the process of surgical implantation and postoperative recovery, resulting in adverse reactions of surrounding tissues, and even implant failure [10–12].

Since both osteointegration and bacterial infection occur on the surface of implants, the preparation of coatings on the surface of Ti metal is currently the most widely used and most mature modification method in clinical applications [13–15]. The preparation of surface coating can not only maintain the excellent mechanical properties of Ti implants, but also endow them with many desirable properties [16]. Hydroxyapatite (HA) is the main inorganic component of human bone tissue, which has osteo-conduction and osteo-induction functions [17]. It is commonly used as an excellent coating for imparting biological activity to Ti-based implants. Many studies have confirmed that Ti-based implants with HA coating perform good osseointegration ability and can effectively accelerate the rate of osseointegration [18]. At present, the HA coating preparation processes mainly involve sol-gel [19], electrodeposition [20], plasma spraying [21], and so on. The preparation of HA coatings under different conditions has become one of the research hotspots of biomedical bone materials in recent years. Fig.1(a) shows the common antibacterial methods of implants, mainly including reducing bacterial adsorption, contact with antibacterial medicine, and the release of antibacterial particles [22]. There are two main methods to reduce the adsorption of bacteria: (i) through the micro-nano surface coating morphology, which greatly reduces the adhesion of bacteria [23‒24]; (ii) through the antifouling agent coating to effectively reduce most of the attachment of protein-coated bacteria to material surfaces [25‒26]. However, the low antibacterial effect and bacterial adhesion of non-protein coat species are important factors to limit its clinical use. Contact antibacterial, as the name implied, requires antibacterial materials to contact bacteria to destroy their normal morphology and physiological structure to inhibit bacterial growth or even kill bacteria, which mostly occurs on the surface of coatings such as antimicrobial peptides or metal oxides [27]. Heavy metal particles, singlet oxygen and hydroxyl radicals are substances that can effectively kill bacteria on the surface of materials [28]. At the same time, due to the photothermal effect of some coatings, the increase of the surface temperature of Ti-based implants through the irradiation of near-infrared (NIR) light is also an effective way to inhibit bacterial growth, kill bacteria, and even remove bacterial biofilms [29].

Fig.1 (a) Schematic diagram of antibacterial methods and possible applications, and (b)(c)(d) schematic diagram of the antibacterial principle of metal NPs. Reproduced with permission from Refs. [30–32].

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Metal nanoparticles, as the most common component of antibacterial coatings, their antibacterial mechanism has also been widely investigated in Fig.1(b)‒Fig.1(d) [30–32]. Silver nanoparticles (Ag NPs) are believed to be the release of Ag⁺ that can penetrate the interior of bacterial cells, leading to the rupture of early lysozyme. It not only induces intracellular free radical oxygen species (ROS) damage DNA and RNA chains, but also directly damages DNA and RNA to inhibit bacterial proliferation [33]. Zinc oxide nanoparticles (ZnO NPs) and copper (Cu) NPs can reduce the initial antibacterial adhesion, and effectively destroy the normal external structure of bacteria [34]. The release of ROS and hydroxyl radicals also damage the internal DNA and RNA [35‒36].

Aiming at the defects faced by the clinical application of Ti-based implants, the researchers combined the bioactive HA used for bone tissue repair with different antibacterial materials to prepare composite coatings, which will fundamentally solve the problem of the clinical application of Ti-based implants. In recent years, researchers have made some progress in the research of antibacterial HA coatings on Ti implants. The preparation methods can be divided into two categories, namely one-step method and multi-step method (Fig.2). In this paper, the different preparation methods were summarized, and the most relevant studies and the latest status of research in this area were reviewed.

Fig.2 Schematic diagram of antibacterial HA coatings on Ti implants prepared by one-step and multi-step methods to kill bacteria and promote osteogenic differentiation.

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2 One-step method

In the one-step method, we focus on the method of introducing antibacterial agents in the process of preparing HA coatings. The one-step method can better adapt to the large-scale industrial production in the market, improve the utilization rate of the machine, and reduce the problem of product cost increase due to the cumbersome preparation process.

2.1 Electrodeposition

Electrodeposition, as a common method for preparing HA coatings, is also widely used to prepare composite coatings in one-step [37‒38]. Electrodeposition mainly includes electrochemical deposition and electrophoretic deposition. The main difference of them is the form of the electrolyte. The electrolyte used for electrochemical deposition is usually a salt solution of a mixture of target products. However, electrophoretic deposition generally refers to the formation of dissolved colloids in suspension. Under the action of the electric field, the two-part work of electrophoresis first and deposition later is carried out [39].

Compared with other preparation methods, the operation of electrochemical method is simple, the equipment is cost effective, the coating can be formed on the irregular inner surface, its performance can be well controlled by changing the parameters, and the low-temperature deposition process is relatively fast, avoiding the generation of many thermal defects advantage [40]. Using electricity or pH, some functional compounds such as silicon, graphene oxide (GO), and paclitaxel can be co-deposited with HA on Ti implant surface, but the obtained antibacterial ability is very limited [41–44]. To further enhance the anti-infection ability that Ti metal itself lacks, Ag NPs have been introduced into the HA coating [45–47]. Ag NPs and ions are heavy metal particles that are generally considered to have a strong antibacterial ability. Researchers found that Ag NPs can be easily introduced into the HA coating by electrodeposition method, effectively enhancing the antibacterial ability of the composite coating [48–50].

As shown in Fig.3(a), under the action of the electric field, it is difficult for Ag NPs to be uniformly dispersed and deposited on the surface of the Ti substrate [51]. Therefore, researchers co-precipitated Ag NPs with chitosan (CS) as a combination with HA on the surface of Ti substrates. As a cationic natural biomacromolecule, CS has good biocompatibility, and the electrostatic repulsion between CS molecules also uniformly distributes Ag NPs in the coating by preventing their aggregation (Fig.3(b)) [52]. At the same time, since CS can form coordination compounds with Ag NPs, which can effectively slow down the release rate of Ag⁺ (Fig.3(c)), prolong the antibacterial time, achieve long-term antibacterial ability, and reduce cytotoxicity. Furthermore, CS is positively charged, which makes this material prone to bind to negatively charged bacterial cell walls and attach to DNA to inhibit bacterial replication [53]. Due to the different antibacterial mechanisms, CS and Ag NPs synergistically optimize the antibacterial ability of the coating.

Fig.3 (a) Ag inhomogeneous agglomeration under the action of an electric field. Reproduced with permission from Ref. [51]. (b) Ag is uniformly distributed without agglomeration after adding CS, and (c) Ag release rate under CS confinement. Reproduced with permission from Refs. [33,52].

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Not only Cu has less biological toxicity than Ag, but Cu ions are also a trace element needed by the human body, which can contribute to the cross-linking of collagen and elastin in bone [54]. When the concentration of Cu exceeds a certain threshold, it is also toxic to human cells [55]. Reducing the clusters of Cu NPs to slows down the release of Cu ions can effectively control cytotoxicity. However, the antibacterial ability of Cu is weaker than that of Ag, so reducing the release of Cu ions will also affect the antibacterial effect, and it is particularly important to balance toxicity and antibacterial ability. Huang et al. replaced Cu and Sr with a similar radius of Ca ions to form HA by doping to effectively control the adverse effects of Cu ions, while also had good biocompatibility and bone repair ability [56]. Wang et al. used the complexation of amine ions in polypyrrole (PPy) with Cu ions to make the distribution of Cu NPs more uniform while slowing the release of Cu ions, and good antibacterial ability was observed [57].

In the past two decades, ZnO has attracted attention in various fields due to its multifunctional properties [58]. It is easy to introduce ZnO into the HA coating by the electrochemical method, as shown in Fig.4(a). ZnO is an n-type semiconductor with a wide band gap and high bond energy [59]. The U.S. Food and Drug Administration (FDA) has declared ZnO a generally recognized as safe (GRAS) compound, paving the way for ZnO biomedical applications [60]. It is also one of the excellent bone repair materials due to its satisfactory mechanical properties and osteogenic activity [61]. One of the applications of ZnO NPs is for wound healing dressings, as they exhibit strong antibacterial ability against both Gram-positive and Gram-negative bacteria [62]. However, like numerous metal nanoparticles, the cytotoxicity of ZnO NPs to mammalian cells is still under investigation and no consensus has been reached in this context [63]. One of the effective factors appears to be the size of the NPs. As they become smaller, the total surface area increases, thereby increasing their antibacterial efficiency, but their toxicity also increases [64]. Concentration is hypothesized to be another effect, with low doses being beneficial and high doses possibly increasing the risk of side effects [65]. However, neither safe size distribution nor concentration has been reliably found, so research is still ongoing. In addition to the incorporation of heavy metal NPs and their oxides, potential applications of antibacterial coatings such as antimicrobial peptides have also been partially reported [66].

Fig.4 (a) The flow chart of electrochemical loading of ZnO. Reproduced with permission from Ref. [60]. (b) SEM images of the coatings made by PEO at scale bars of 10 μm (i) and 5 μm (ii); SEM images of the MRSA strain cultured on uncoated and coated Ti samples at the scale bar of 5 μm (inset: 1 μm) (iii). Reproduced with permission from Ref. [68].

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The full name of MAO is micro-arc oxidation, also known as plasma electrolytic oxidation (PEO). It is a coating method that combines anodization technology with electrochemical technology. Compared with the coatings fabricated by electrochemical deposition and electrophoretic deposition, PEO coating has small pores, no cracks, good corrosion resistance, and strong bonding strength [67]. First, a passive film or a porous insulating oxide film is formed. Then, under the action of spark discharge and strong arc discharge, the newly formed oxide coating gradually forms and thickens. Finally, with the continuous formation and breakdown of the oxide coating at the large discharge channel, a porous ceramic oxide coating is formed as shown in Fig.4(b) [68]. The chemical composition of the PEO coating is affected by salts in the electrolyte [69–71]. Therefore, it also provides feasibility for the introduction of functional particles. NPs embedded in an oxide matrix from an electrolyte can be used to coat implants with more complex surface morphologies [72]. Mixing antibacterial ingredients into the electrolyte can make the prepared coating have the antibacterial ability [73–75]. However, there are not many studies on the composite antibacterial HA coating prepared by PEO at present, and the preparation of composite HA from PEO will also be a worthy part of electrodeposition in the future. Obviously, pre-treatment of the substrate material before electrochemical deposition will facilitate the introduction of more antibacterial means. As shown in Fig.5, the Ti-based material was pre-loaded with tannins before electrochemical deposition, and the antibacterial element GO was loaded through the π−π bond, while providing nucleation sites to promote the generation of HA. In addition, the abundant hydroxyl groups of tannins will provide the possibility of later collagen (COL) loading [76]. Compared with traditional electrochemical deposition, the method of pretreatment will provide more possibilities.

Fig.5 (a) The production scheme of HA‒GO‒COL composite coating on Ti 16Nb alloy surface, and (b) the schematic diagram of coating combined. Reproduced with permission from Ref. [76].

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Electrochemical deposition methods also have some drawbacks. The main problem is the low bond strength between the coating and the substrate. One of the reasons for the low bonding strength is that when electrons are obtained at the cathode, water will be decomposed and reduced, and the generated gas will make the coating uneven, reduce the quality of the coating, and reduce the bonding strength with the substrate [77]. Also, the PEO technology needs to be done at high voltages, so when larger samples are processed, the increase in current can cause the system to heat up. In this case, the electrolyte in the treatment tank must be forced to cool, otherwise the electrolyte will generate too much heat and the uniformity and effectiveness of the coating cannot be guaranteed [78].

2.2 Sol-gel method

It is difficult to introduce both antibacterial cations and bone repair cations for electrodeposition because cations need to compete with anions in the electrolyte to form binding sites [79]. Therefore, the sol-gel method is particularly important, and coatings are widely used for surface modification of Ti and its alloys due to their low cost, low sintering temperature, and easy preparation of uniform hybrid or multilayer coatings [80‒81]. The sol-gel derived coatings not only have excellent biocompatibility, but also have a large specific surface area and inner surface, and their rich chemical composition makes it easy to use suitable biomolecules [82]. The sol-gel method uses compounds containing highly chemically active precursors, and these raw materials are uniformly mixed in the liquid phase, and the chemical reactions of hydrolysis and condensation are carried out to form a stable and transparent sol system in the solution. The material is immersed in the gel solvent, and the gel is adsorbed by physical means including centrifugal force spin coating [83], dipping [84‒85], and so on (Fig.6(a)‒Fig.6(c) [86]). Like electrodeposition, the gel also needs to be cured by sintering to produce a stronger coating. Based on the easy fabrication characteristics of the above-mentioned sol-gel method and the requirements for different properties of implants, the configuration of the sol-gel largely determines the properties of the prepared coatings. The antibacterial effect of fluorine ions has been previously demonstrated [87]. Batebi et al. introduced F ions into the antibacterial compound AgF to reduce the release of Ag⁺. The Ag⁺ release amount was reduced but the antibacterial effect was improved [88‒89]. It is due to the synergistic antibacterial effect of F⁻. As shown in Fig.6(d), studies have shown that F⁻ can attach to the bacterial wall, rupture the cell membrane, generate reactive oxygen species, change the normal physiological activities in the bacteria, cause cytoplasmic leakage and lead to bacterial death [90‒91]. At the same time, F⁻ is an essential component in human bone [92]. A small amount of F⁻ does not only cause weak cytotoxicity, but also promotes the repair of bone tissue, which is a promising antibacterial method.

Fig.6 (a)(b)(c) The schematic diagram of coating preparation by sol-gel method. Reproduced with permission from Ref. [86]. (d) Schematic diagram of the antibacterial mechanism of F ions. Reproduced with permission from Ref. [90].

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The preparation of cationic lattice-substituted HA coatings is also characteristic of the sol-gel method. Bi et al. [93] prepared Zn‒HA by using Ca(NO₃)₂·4H₂O and Zn(NO₃)₂·6H₂O dissolved in ethanol to form solutions, respectively. Use a magnetic stirrer to disperse the sol evenly on the surface of the Ti substrate and then calcined at a high temperature for reinforcement. The prepared coating also has the good antibacterial ability. However, the sol-gel method has disadvantages such as high permeability, low abrasion resistance, and difficulty to control porosity, which also limits its application in this field. The maximum coating thickness of the crack-free coating is only 0.5 mm. Recent advances in highly refined sol-gel substrates are also affected by thermal expansion mismatch. Nonetheless, there is still much room for improvement in this technique, and further research should be carried out to improve this promising method for coating biomaterials [94].

2.3 Plasma spraying

Plasma spraying technology often plays a crucial role in the preparation of metal surface coatings due to its simplicity of operation [95] and technical maturity [96] and is the only commercialized FDA-approved coating technology [97]. Plasma spraying technology is to use a heat source to heat ceramics, alloys, metals, and other materials to a molten state under the protection of inert gas and spray them on the surface of the pretreated workpiece at high speed. In the traditional plasma spraying process, it is necessary to ensure that the added powder has a suitable particle size range and good fluidity. Therefore, in the process of preparing hyaluronic acid powder from HA by grinding, spray granulation and sieving, it is inevitable to waste raw materials. The researchers improved and invented the suspended plasma spraying (SPS) technology as shown in Fig.7(a), which formed a plasma jet by injecting F ion-substituted HA suspension liquid raw materials. SPS reduced the material loss during the powder preparation process, and at the same time, due to the reduction in particle size, more microscopic materials can be prepared. Mechanisms by which F⁻ may interfere with bacterial metabolism and plaque acidification as a potent antibacterial agent include inhibition of the glycolytic enzymes’ enolase and proton-extruding ATPase as well as bacterial colonization and competition [92]. In addition, different powers of plasma spraying will affect the release of ions in the coating. Through degradation experiments, it is found that the coatings prepared by spraying with lower power are more easily degraded, so it can explain that when the power is 35 kW, the coating has the best antibacterial ability [98]. Besides improving the plasma spraying equipment, the spraying technology can also be improved. Ke et al. [99] used the laser engineering network forming technology (LENS^TM) to prepare the gradient HA coating on the substrate (Fig.7(b)). To a certain extent, the problem of low bonding strength of the coating caused by the mismatch of thermal expansion coefficients is solved, and the release rate of Ag⁺ is controlled to a certain extent, and the cytotoxicity is reduced.

Fig.7 (a) The schematic diagram of suspension plasma spraying and its different antibacterial abilities at different powers, and (b) the schematic diagram of the coating prepared by the LENS^TM method and its release of Ag ions and its antibacterial effect. Reproduced with permission from Refs. [98‒99].

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To better control the release of antibacterial agents and balance cytotoxicity and antibacterial ability, there are two common methods. The one is controlling the stability of the crystal structure of the coating or control the degradation rate of the coating to tailor the antibacterial ability. The researchers blended Sr, Zn, and HA to prepare coatings. After sintering at 500 and 600 °C, adjusting the crystal structure of HA had a huge impact on the release of Ca, Sr, and P ions. The release of ions will in turn determines the release of Zn ions [100]. Another one is to control the composition in the coating by controlling the concentration of the mixed antibacterial agent [101]. Most of the natural bone in the human body is porous, which facilitates internal mass exchange and bone growth [102]. Therefore, with the continuous development of implant technology, the preparation and processing of implant materials into three-dimensional (3D) porous structures can not only provide sufficient space for bone growth, but also promote internal mass exchange [103] and reduce the occurrence of stress shielding effects [104], which collectively increase the survival probability and service life of the implants. However, the traditional plasma spraying technology can only spray on the surface of the material and cannot effectively spray the coating into the porous interior of the material, although Xu et al. [105] filled nano-HA particles into porous Ti matrix to prepare HA coating under the action of vacuum suction. However, there are few reports on the preparation of composite HA coatings with antibacterial ability by vacuum spraying, which provides a future research direction for plasma spraying.

2.4 Selective laser melting and magnetron sputtering

HA prepared by plasma spraying and electrodeposition often suffers from coating due to low bonding strength, resulting in coating peeling and implant failure. Unlike plasma spraying, laser melting is a representative technology of 3D printing (rapid prototyping) [106]. The coating is first spread on the surface of the substrate and then bonded to the Ti substrate by laser melting and sintering [107‒108]. It also possesses significant advantages such as selective process control, high power density, high process efficiency, cleanliness, and automation [109]. It solves the technical problem that the traditional hot working coating preparation process lacks flexibility in the fusion of raw materials and complex geometries. It has been successfully applied in the biomedical field [110]. Obviously, this method can also easily prepare a composite HA coating with antibacterial ability. The HA powder and Ag powder are mixed with the binder polyvinyl alcohol (PVA) to prepare the coating precursor and then melted to make it highly bonded to the Ti substrate surface [111]. The antibacterial ability of the coating prepared by this method is relatively weak, which may be due to the high binding strength, which makes the antibacterial components difficult to release, or the inclusion of HA dilutes the concentration of antibacterial particles. At the same time, due to the highly processable nature of selective laser melting (SLM), some researchers have reduced the adhesion of bacteria by designing the surface roughness of the coating to play an antibacterial effect and reduce the potential toxicity of antibacterial agents [112]. At present, some studies have also reported the preparation of coatings by magnetron sputtering, which has three main advantages. First, a dense and uniform coating with a controllable thickness can be obtained. Second, a thin film that is tightly bonded to the substrate can be formed [113‒114]. Third, sputtering is a non-equilibrium process, so multiple ingredients can be easily used to add elements into the coating [115] and it was found that the morphology of the coatings can be varied by changing the angle of radiofrequency (RF) [116]. However, there are not many studies on related antibacterial composite coatings, and the influence of different coating forms on the effect of different antibacterial particles is also worth considering by researchers.

3 Multi-step method

Compared with the composite HA coating prepared by the simple one-step method, the method of introducing additional antibacterial substances before or after the HA coating is prepared to make the composite coating have a certain antibacterial ability is called multi-step. Coatings produced by the multi-step method have more flexible preparation methods and richer antibacterial means and may be used in combination with other fungicides to reduce or eliminate the use of prophylactic antibiotics known to lead to the development of antibiotic-resistant bacterial strains. The introduction of common antibacterial capabilities is mainly divided into the following three ways: hydrophilic (hydrogen bonding)/hydrophobic interaction, chemical bonding, and physical adsorption.

1) Hydrogen bonding: Since CS is a hydroxyl group, it is a reliable method to prepare a composite coating on the surface of HA by hydrogen bonding adsorption to increase the antibacterial ability of the implant. Li et al. [117] used HA as an interlayer between CS and Ti substrates. Compared with the loading of CS on pure Ti [118], the presence of a large number of hydrogen bonds in HA can make CS have better dispersion and uniformity. However, less CS represents a weaker antibacterial ability. Increasing the concentration of CS will enhance the antibacterial effect. However, too much HA micro-covering loses the nanostructure and HA will reduce the biological properties of the material to a certain extent. Palierse et al. [119] prepared a Ti-based HA coating, loaded with natural antibiotic baicalein, and interconnected by hydrogen bonds of hydroxyl groups. Although baicalein as a natural antibiotic has a good killing effect on resistant bacteria, its killing effect on sensitive bacteria is not as effective as compound antibiotics. At the same time, the low solubility in water also limits its loading on HA, which greatly limits its use in antibacterial.

2) Chemical bonding: In Fig.8, we summarize the preparation methods of two antibacterial HA coatings using chemical bonding as the linking mode. Luo et al. [120] oxidized pyrrole (Py) in situ to form PPy as a mediator between HA and metal ions, and PPy was mixed with the phosphate of HA. The amine groups on PPy are combined with metal ions, and at the same time, due to the electrochemical pulse method, part of the metal ions is reduced at the cathode to metal nanoparticles and adsorbed on the surface of the material. The results show that the combination of Cu, Ag or ZnO can exhibit good antibacterial ability. Li et al. [121] fabricated HA nanorods on the Ti surface by co-doping Fe and Si, and then grafted antimicrobial peptides through polymer brushes. A chemically combined antimicrobial peptide HA composite coating with high grafting rate was successfully obtained.

Fig.8 (a) The schematic diagram of hybrid complexation with phosphate ion. Reproduced with permission from Ref. [120], and (b) the schematic diagram of the polymer brush grafted antimicrobial peptide on HA nanorods. Reproduced with permission from Ref. [121].

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3) Physical adsorption: Simply using CS for antibacterial has a very limited antibacterial ability. Therefore, many researchers will add additional antibacterial substances to enhance their antibacterial ability when using CS. The good biological activity of sugar can effectively reduce the killing of normal cells by antibacterial substances. Wang et al. [122] loaded ZnO on the Ti substrate to enhance the antibacterial ability before introducing the composite coating of HA and CS, and used the physical reaction of solvent casting and evaporation to composite HA and CS. The introduction of the coating into the surface can also reduce the toxic and side effects of ZnO on normal cells to a certain extent. Electrodeposition is also one of the common physical adsorptions. Ghosh et al. [54] used electrochemical methods to deposit HA coating on Ti substrates, and then used similar methods to reduce Cu ions of different concentrations into nano-Cu, which was loaded on the Ti substrate. In addition, charge adsorption is also a common preparation method. Ivanova et al. [123] firstly prepared negatively charged Ag NPs and then sprayed HA on the surface of the Ti substrate by RF method to prepare a simple and effective antibacterial composite coating. At the same time, the coating can compensate for the disadvantage of the rapid release rate by adjusting the structure and thickness of the HA coating, achieving durable antibacterial advantages similar to which Surmeneva et al. [124] also controlled the release of the antibacterial coating thickness. However, whether the coating obtained by simple physical deposition is firm and effective needs to be confirmed by more tests and clinical experience. Tab.1 summarizes the advantages and disadvantages of three common multi-step methods for the preparation of composite antibacterial HA coatings [125–127].

Tab.1 Advantages and disadvantages of common multi-step methods for preparing composite antibacterial HA coatings [125–127]

Method	Advantage	Disadvantage
Hydrogen bonding	Slowing down the release of metal antibacterial ions, and reducing toxic and side effects [125]	Limited choice of antimicrobials
Chemical bonding	Forming chemical bonds to coat firmly	Reduced repair ability of original bone and biocompatibility of HA
Physical adsorption	Easy to combine, easy to operate [126]	Weak binding ability, weak coating adhesion, and fast release rate of antibacterial substances [127]

4 Conclusion

The composite antibacterial HA coating is prepared by various means such as plasma spraying and electrodeposition, which can not only effectively improve the biocompatibility of the implant and induce osteogenic differentiation, but also give Ti implants certain antibacterial ability. Many studies have shown that this composite HA coating can effectively reduce the cytotoxicity caused by the excessive release of metal ions by doping, which is a choice for both antibacterial ability and cytotoxicity. However, this composite antibacterial HA coating also has certain problems. (i) The stability of the coating and the bonding strength of the coating to the implant have always been important issues for researchers. Most of the composite HA coatings prepared by the above methods cannot be strongly bonded to the substrate, and the stability of the coating is an important factor that directly affects whether the coating can play a role in the human body after implantation, and also directly affects the implantation effect. Therefore, it is necessary to improve the bonding strength between the coating and substrate. (ii) Common antibacterial methods, especially the introduction of metal ions and antibiotics, show good antibacterial ability in the initial stage of implantation. The antibacterial ability will gradually decline, so it is very difficult to achieve long-term antibacterial, and it is also the direction that researchers need to further explore in the future. (iii) Although heavy metal particles generally have the strong antibacterial ability, high concentrations will also cause potential toxicity risks to organisms. Therefore, it is necessary to effectively control the release rate of particles to avoid local concentrations caused by the agglomeration of heavy metal particles. (iv) There are various ways of antibacterial methods, but the method of simple preparation of composite antibacterial HA coating is mostly limited to the doping of heavy metal particles. The blended composite coating of peptides and antibacterial drugs and HA needs further research.

In recent years, with the development of oral prosthodontics more and more new coating materials and coating preparation techniques will attract people’s attention. Excellent dental implants not only need to meet the requirements of rapid bone repair but also have long-term antibacterial ability. In order to meet more clinical needs, relieve patients’ pain, and ease the burden of doctors, it will undoubtedly be possible to prepare multi-functional coatings with anti-oxidation, pro-angiogenesis, and nerve repair properties through more modification methods.

Disclosure of potential conflicts of interests

The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 12272253, 11632013, and 11902214) and the Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering (Grant Nos. 2021SX-AT008 and 2021SX-AT009). The support of the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province (Grant No. 20220006) is also acknowledged with gratitude. Thanks to BioRender for help on some pictures.

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