The latest statistics show that by mid-century, the global population aged 65 or over is expected to more than double to a staggering 1.6 billion people [1]. An aging population means a larger population base of chronic diseases, and bone and joint diseases. In dentistry and orthopedics, implants, with titanium (Ti) and its alloys as the preferred choice among various materials, have become a common approach for treating conditions due to their exceptional biocompatibility and mechanical properties [2]. Despite the vast potential for Ti and its alloys, there are still limitations to surface bioactivity. They often exhibit biological inertness, limiting the close integration of implants with surrounding tissues. Furthermore, Ti alloys are susceptible to microorganisms, increasing the risk of postoperative infections, and threatening the prognosis of patients. To tackle these issues, apart from alloying ^[3][4][5][3,4,5], surface treatment proves to be an effective approach as well. Common methodologies encompass atmospheric plasma spraying [6], laser treatment [7], anodizing [8], micro-arc oxidation (MAO), and biomimetic deposition of apatite [9] or other biomaterials [10]. Among the various surface modifications available, MAO has garnered significant attention due to its simplicity of operation, cost-effectiveness, and applicability to complex devices. Through MAO, the surface of Ti-based implants can undergo alterations in microstructural features and chemical composition, rendering them more suitable for tissue adhesion and effectively reducing the risk of infections [11].

2. Applications

MAO coatings, particularly with specific functional additives, possess remarkable biological functionalities including bone promotion, antimicrobial properties, and anti-inflammatory effects. Though clinical applications of Ti-based implants with MAO-modified functional coatings are limited, animal experiments have validated several implants with such coatings (Table 13). Presently, surface modification techniques like sandblasting, acid etching, and anodization, along with the introduction of bioactive materials such as calcium phosphate, hydroxyapatite, and calcium nanoparticles, are widely employed to optimize implant surface microstructure and topography. These modifications primarily aim to enhance biocompatibility and promote osseointegration. For example, MAO techniques have been utilized to create rough and porous surfaces on dental implants and femoral stems, facilitating improved tissue bonding ^[12][119]. Coatings contain different components with different biological functions and are validated in vitro and in vivo.

Number	Biologic Function	Adding Substances	Technique	In Vitro		In Vivo	Conclusion/Remark	Reference
				Cell	Bacterium	Animal Parts
1	Osteogenesis	Ca, Sr	MAO	hBMSCs			Simultaneously incorporating Ca and Sr demonstrated superior promotion of hBMSC proliferation.	[13][97]
2	Osteogenesis/Angiogenesis	Zn	MAO	HUVECs and BMSCs			In the Zn2+ environment, angiogenesis and osteogenesis mutually promote each other.	[14][106]
3	Osteogenesis/Angiogenesis	Hydroxyapatite nanotubes (HNTs)	MAO	HUVECs and MC3T3-E1 cells			HNT specimens promote both angiogenesis and osteogenesis on cellular and molecular levels.	[15][101]
4	Osteogenesis	B	MAO, hydrothermal treatment, and heat treatment	SaOS-2 cells			Nanorods inhibit SaOS-2 cell activity, whereas nanoparticles promote it.	[16][143]
5	Osteogenesis	Hierarchical coatings	MAO, electrochemical reduction	BMSCs		Beagle dogs, the shaft of the canine femur	The hierarchical coatings show higher osteogenesis rates compared to the ordinary MAO group.	[17][113]
6	Osteogenesis	HA, BMP-2	MAO, dip coating	MC3T3-E1 cells		Beagle femur	The interface bonding strength between HA/BMP-2 coating and surrounding new bone tissue is higher than that of Ca/PMAO coating.	[18][109]
7	Osteogenesis/Angiogenesis	Ca, P, BMP-2	3D printing, sandblasting etching, MAO, electrochemical deposition	BMSCs		New Zealand White Rabbit Skull	MAO-CaP-BMP-2 is superior to the MAO and MAO-CaP groups in new bone formation.	[19][117]
8	Osteogenesis/Antibacterial	Ca, P	MAO	hFOBs	E. coli and S. aureus		Volcanic-crater-like and needle-like CaP structures form at 350 V and 450 V, respectively. The former exhibits superior antibacterial performance and biocompatibility.	[20][121]
9	Bioactivity/Antibacterial	Ca, P	MAO, UV catalysis	HGFs	S. sanguinis		Photofunctionalization reduces hydrocarbons and enhances surface protein adsorption.	[21][125]
10	Osteogenesis/Antibacterial	Zn	MAO	MC3T3-E1 cells	E. coli		Incubation with salt solution converts Zn ions into zinc oxide, which helps with long-lasting antibacterial activity.	[22][134]
11	Antibacterial/Osteogenesis/Angiogenesis	Sr, Zn	MAO	HUVECs, BMSC	MRSA and P. gingivalis	Rat femoral model	The surface osteogenesis of samples doped with Sr and Zn is superior to other groups. (No in vivo antibacterial test conducted.)	[23][104]
12	Antibacterial	Ag, Cu NPs	MAO	MC3T3-E1 cells	MRSA	Mouse femur ex vivo experiment	Ag and Cu ions synergistically kill bacteria, allowing a 10-fold reduction in Ag ion concentration with consistent antibacterial efficacy.	[24][124]
13	Osteogenesis/Antibacterial	Ag, Zn	3D printing, MAO	MC3T3-E1 cells	MRSA	Mouse femur ex vivo experiment	The synergistic effect of Ag and Zn reduces the concentration of Ag+ by 120 times.	[25][128]
14	Osteogenesis/Antibacterial	Ag, Zn	MAO	MC3T3-E1 cells	S. aureus		Ag and ZnO synergy enhances antibacterial performance and promotes CaP phase formation.	[26][129]
15	Osteogenesis/Antibacterial	Ag, Zn	MAO	MC3T3-E1 cells	S. aureus		Ag and Zn ion release is above the antibacterial threshold yet well below cytotoxic levels.	[27][130]
16	Osteogenesis/Antibacterial	Ag, Zn	MAO		S. aureus		Ag and Zn have good synergistic antibacterial effects.	[28][131]
17	Osteogenesis, Antibacterial	Cu, Zn	MAO	MG63	E. coli, S. aureus, and MRSA		Orthogonal experiments explore electrolyte effects on coatings, with phytic acid supplying the P element.	[29][132]
18	Skin-integration/Antibacterial	Cu, Zn	MAO	Fibroblasts (L-929)	S. aureus		The synergistic effect of Cu and Zn facilitates skin integration and antibacterial activity.	[30][133]
19	Osteogenesis, Anti-tumor/Antibacterial	Se	MAO	BMSCs, cancerous osteoblasts	S. aureus and E. coli		Se doping enhances osteogenic, anti-tumor, and antibacterial properties.	[31][103]
20	Osteogenesis/Antibacterial	Mn	MAO	MC3T3-E1 cells	E. coli	Rabbit femur	The coating induces osteogenesis and promotes osseointegration.	[32][137]
21	Antibacterial	Bi	MAO	MG63 cells	A. actinomycetemcomitans, MRSA		Bismuth nitrate has excellent antibacterial activity compared to bismuth acetate, bismuth gallate, and silver nitrate.	[33][138]
22	Osteogenesis/Antibacterial	Ce	MAO	BMSCs	P. gingivalis, S. aureus	Osteoporotic rat hind legs	Ce-TiO2 coating has excellent antibacterial and anti-inflammatory properties.	[34][139]
23	Antibacterial	I	MAO, HT, photocatalysis	BMSCs	S. aureus	Tibial Intramedullary Infection Model of Rats	Under NIR, the coating has good antibacterial and osteogenic properties.	[35][140]
24	Antibacterial	I	MAO, electrophoresis	BMSCs	S. aureus and E. coli	The rat osteomyelitis intramedullary nail model	Thirty days after implantation, excellent antimicrobial ability was verified.	[36][141]
25	Bioactivity/Antibacterial	B	MAO	ADSCs	S. aureus and P. aeruginosa		Add a small amount of sodium tetraborate to the Ca, P electrolyte system.	[37][142]
26	Osteogenesis/Antibacterial	F	MAO	BMSCs	S. aureus and E. coli	Rabbit femur	Coatings with high F addition showed improved antibacterial and osteogenic abilities.	[38][144]
27	Antibacterial/Osteogenesis/Angiogenesis	Sr, Co, and F	MAO	BMSCs	S. aureus and E. coli	Rabbit femur	Sr, Co, and F co-doped coatings induce osteogenesis.	[39][145]
28	Osteogenesis/Antibacterial	Mn, F	MAO	BMSCs	S. aureus		Mn and F co-doped coatings show excellent wear and corrosion resistance, along with strong antibacterial properties.	[40][146]
29	Osteogenesis/Antibacterial	Cu, BMP-2	MAO, dip coating	MC3T3-E1 cells	E. coli, MRSA, Neurospora crassa, and Candida albicans	Mouse craniotomy model	The coating significantly promotes osseointegration.	[41][110]
30	Osteogenesis/Antibacterial	Ag, HA	MAO, RF-MS	MC3T3-E1 cells	E. coli		This coating exhibits strong biological activity and antibacterial properties.	[42][111]
31	Bioactivity/Antibacterial	Ag NPs, polylactic acid (PLA)	MAO, electrospinning	MC3T3-E1 cells	S. aureus		PLA ultrafine fibers produced by electrospinning can control the release of silver ions.	[43][149]
32	Osteogenesis/Antibacterial	AgNPs, polydopamine	MAO, dip coating	MG63 cells	S. aureus	New Zealand rabbit subdermal implantation	This coating exhibits strong biological activity and antibacterial properties.	[44][122]
33	Osteogenesis/Antibacterial	Polydopamine, cationic antimicrobial peptide LL-3, phospholipid	MAO, dip coating	BMSCs and OBs	S. aureus and E. coli		The coating exhibits good osteogenesis and antibacterial properties.	[45][147]
34	Antibacterial	GO	MAO, EPD		S. aureus and E. coli		Achieves ~80% antibacterial activity against E. coli and 100% against S. aureus.	[46][151]
35	Antibacterial	rGO, Ag NPs	MAO	MC3T3-E1 cells	MRSA		The coating exhibits good osseogenesis and antibacterial properties.	[47][152]
36	Osteogenesis/Antibacterial	HA, chitosan (CS)	MAO, dip coating	MC3T3-E1 cells	E. coli		Higher usage of CS results in decreased biological performance but improved antimicrobial performance.	[48][153]
37	Osteogenesis/Antibacterial	HA, CS hydrogel containing ciprofloxacin	MAO, HT, chemical grafting	hBMSCs	S. aureus and E. coli		The coating exhibits good osseogenesis and antibacterial properties.	[49][154]
38	Osteogenesis/Antibacterial	BMP-2/CS/HA	MAO, dip coating	MC3T3-E1 cells	E. coli		CS encapsulation sustains BMP-2 release with added antibacterial properties.	[50][115]
39	Antibacterial	Vancomycin	MAO, dip coating			The rabbit osteomyelitis model (infection with MRSA)	In vivo studies demonstrate the potential of this coating to prevent MRSA infection.	[51][148]
40	Osteogenesis/Antibacterial	Vancomycin	MAO, dip coating, chemical grafting	BMSCs	S. aureus	Rat femur	Functional coatings prevent prosthesis infection and promote bone integration at the interface.	[52][155]
41	Antibacterial	Mesoporous silica NPs (MSNs), octenidine (OCT)	Electrophoretic-enhanced MAO	OBs	S. aureus and E. coli		The coating exhibits good osseogenesis and antibacterial properties.	[53][156]
42	Bioactivity/Antibacterial	N, Bi	MAO, photocatalysis	HGFs	Streptococcus sanguinis and Actinomyces nasseri		The coating has bactericidal properties under visible light.	[54][123]
43	Osteogenesis/Antibacterial	MoSe2, CS	MAO, electrospinning, photocatalysis	MC3T3-E1 cells	S. mutans	Rat tibia	Adding MoSe2 significantly enhances TiO2 coating photothermal and photodynamic capabilities.	[55][161]
44	Skin-integration/Antibacterial	β-FeOOH, Fe-TiO2	MAO, HT, photocatalysis	Mouse fibroblasts (L-929)	S. aureus	Mouse skin infection model	The β-FeOOH/FeTiO2 heterojunction prevents bacterial infection under light irradiation.	[56][108]
45	Osteogenesis/Anti-inflammatory	Ca, Si	MAO	SaOS-2 cells			The coating inhibits inflammation and induces M2 macrophage polarization.	[57][167]
46	Antibacterial/Immunoregulation	Cu	MAO	RAW 264.7 macrophages, SaOS-2 cells	S. aureus		Cu boosts macrophage-driven osteogenesis and antibacterial activity in biomaterials.	[58][168]
47	Osteogenesis/Anti-inflammatory	Zn	MAO	RAW264.7 macrophages, BMSCs			The coating shows good osteogenic and anti-inflammatory properties.	[59][169]
48	Osteogenesis/Anti-inflammatory	Mg	MAO	RAW 264.7 macrophages			Mg acts as an anti-inflammatory agent, inhibiting inflammation and promoting osteogenesis.	[60][170]
49	Anti-inflammatory	Co	MAO	RAW 264.7 macrophages		Mouse air chamber model	Cobalt-loaded Ti exhibits immune-regulatory effects on macrophages.	[61][171]
50	Osteogenesis/Angiogenesis/Anti-inflammatory	Li	MAO	BMDMs, mouse embryonic cell line (C3H10T1/2), HUVEC		Mouse air-pouch model	Low Li doses effectively regulate immunity, and promote osteogenesis.	[62][102]
51	Osteogenesis/Angiogenesis/Anti-inflammatory	HA	MAO, SHT	MC3T3-E1 cells, human umbilical vein fusion cells, RAW 264.7 cells		Rabbit femur	This coating promotes osteogenesis and angiogenesis, and induces M2 macrophage phenotype.	[63][172]
52	Osteogenesis/Anti-inflammatory	HA	MAO, SHT	MC3T3-E1 cells, endothelial cells, RAW 264.7 cells		Rabbit femur	Nanoparticle-shaped HA is beneficial for osteogenesis, angiogenesis, and immune regulation, whereas nanorod-shaped HA is the opposite.	[64][173]
53	Osteogenesis/Anti-inflammatory	SiO2, ZnPs	MAO, sol-gel	MC3T3-E1 cells			The coating shows good osteogenic and anti-inflammatory properties.	[65][175]
54	Osteogenesis/Anti-inflammatory	Sr, silk fibroin-based wogonin NPs	MAO, electrochemical deposition, LBL	RAW 264.7 cells, OBs		Osteoporotic rat femur	The coating shows good osteogenic and anti-inflammatory properties.	[66][176]

TiUnite and TiUltra surfaces(Nobel Biocare, Zurich, Switzerland), along with the Ospol implant(OspolAB, Malmö, Sweden) and the M implant(Shinhung, Seoul, Republic of Korea), are all manufactured using the MAO process and are commercially available. The TiUnite surface series by Nobel Biocare^TM, introduced in the early 2000s, has undergone continuous refinement and gained worldwide acceptance. These implants, containing 7% phosphorus in the form of titanium phosphate chemical bonds, are fabricated using an electrolyte mixture with phosphorus. A comprehensive review ^[67][178] encompassing prospective studies spanning from 2000 to 2016 on the clinical performance of implants featuring the TiUnite surface affirms the high survival rates and favorable maintenance of marginal bone associated with such implants. Incidences of peri-implantitis are notably lower for implants employing the TiUnite surface. Notably, implants with this surface consistently exhibit predictable treatment outcomes across diverse indications. In 2019, Nobel Biocare^TM introduced the TiUltra surface series (Figure 19), which features a progressively rough and porous surface texture extending from the implant collar to its tip, exhibiting excellent hydrophilic properties ^[68][180]. Moreover, the M implants of Shinhung^TM are produced using the MAO method with an electrolyte mixture containing magnesium, resulting in a TiO₂ surface containing magnesium (≤9.3%) and phosphorus (≤3%) ^[69][181]. Similarly, Ospol^TM implants are created using the MAO method with an electrolyte mixture containing Ca, leading to the incorporation of calcium ions (less than 11%) within the TiO₂ in the form of calcium titanium oxide bonds ^[70][182]. Femoral shafts treated with sandblasting and MAO coating are commercially available. For example, the Korean Bencox^TM hip system (Corentec, Seoul, Republic of Korea) has cementless sandblasted femoral stems with MAO coating on the surface (Figure 210). Made from Ti-6Al-4V alloy, it is a double-wedge straight tapered stem with a rectangular cross-section. The coating method of MAO coating is as follows: After Ti plating, the sample is electrochemically oxidized using the MAO process. The sample is subjected to MAO treatment with a DC pulse power supply in an aqueous electrolyte containing Ca and P. In a study by Lim et al. ^[72][179], in a follow-up period of at least 5 years, the MAO-coated sandblasted surface did not demonstrate superiority over primary total hip arthroplasty (THA) with the same femoral component design. While MAO is theoretically known to promote bone growth through calcium and phosphorus binding to the titanium alloy surface, forming thick oxides and nano-porous coatings, its clinical utility has not been confirmed. In a study with 10 years of follow up ^[71][183], 309 cases of THA (involving 256 patients) were performed using the non-cemented Bencox^TM hip joint system. A Kaplan–Meier survival analysis indicated a 10-year survival rate of 97.4% when using revision for any reason as the endpoint, and a survival rate of 98.7% when using aseptic loosening revision as the endpoint. While there was a decrease in the proportion of cases with bone resorption in the follow up, the absence of a control group precludes concluding the ability of MAO coatings to resist bone resorption, despite various studies suggesting their potential for preventing bone resorption. In summary, after a follow-up period of at least 10 years, the outcomes of non-cemented sandblasted and MAO-coated THA tapered wedge stems are satisfactory. The MAO coating cannot only promote bone integration but also improve the wear and corrosion resistance of implants. Khanna et al. ^[73][184] performed cold spraying to deposit an Al metal layer onto a Ti-6Al-4V alloy substrate, followed by heat treatment to enhance adhesion. They then conducted MAO treatment to form a dense α-Al₂O₃ layer on the substrate surface, with a Vickers hardness matching that of sintered alumina used for femoral heads (Figure 311).

3. Challenges

Although MAO coatings have undergone extensive research and led to the emergence of related products, there are still challenges and limitations in the production and application:

• Despite considerable progress in studying the discharge process of MAO, some micro-scale mechanisms remain unclear, such as cathodic discharge and soft spark discharge. This uncertainty affects the control of the microstructure of MAO coatings ^[74][22].
• In the coating manufacturing process, establishing the electrolyte composition and electrical parameters still necessitates multiple experiments. Defining the optimal parameters remains challenging. Minor losses of electrolytes during usage and the settling of particulate or colloidal electrolytes can also impact coating performance ^[75][76][44,54].
• The impact of coating morphology on cell bioactivity remains inconclusive. While some studies suggest that moderate roughness aids in cell adhesion and proliferation, and porous surfaces facilitate cell osteogenic differentiation, there is still debate about the optimal pore size. Different cell types may have varied requirements for morphology ^[77][78][90,91]. Additionally, due to cracks and interconnected pores, their durability and wear resistance require attention ^[79][20].
• Coatings with added functionalities, such as antimicrobial and anti-inflammatory components, may exhibit toxic effects on normal cells, especially with high concentrations of antibiotics or antimicrobial agents ^[12][80][119,164].
• There is a substantial amount of research on biologically functional coatings; the availability of implants in the market is relatively limited. Successfully translating these technologies into commercial products may face greater challenges ^[12][119].