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| REVIEW ARTICLE |
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| Year : 2023 | Volume
: 9
| Issue : 1 | Page : 1 |
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Research progress on surface modification of three-dimensional printing porous titanium alloys
Hongwei Liu, Xinqi Cheng
Department of Orthopedics, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu, China
| Date of Submission | 25-Apr-2022 |
| Date of Decision | 30-Jul-2022 |
| Date of Acceptance | 22-Aug-2022 |
| Date of Web Publication | 11-Jan-2023 |
Correspondence Address:
Hongwei Liu
Department of Orthopedics, The A.liated Changzhou No. 2 People's Hospital of Nanjing Medical University, No.68 Gehu Middle Road, Changzhou, 213003, Jiangsu
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/digm.digm_23_22
Three-dimensional (3D) printed porous titanium alloy has good mechanical and physical properties and chemical stability. It is widely used in the field of additive manufacturing to realize the personalized customization of complex structures, such as industry, military, aerospace, and medicine, especially in the customization of personalized orthopedic implants and the repair and reconstruction of bone defects. However, due to the biological inertia of titanium alloy, the cell adhesion of the untreated metal surface is poor. Therefore, surface modification to enhance the biocompatibility and promote bone activity and antibacterial activity of 3D printed porous titanium alloy has become a research hotspot. In this article, the surface modification technology of 3D printing porous titanium alloys is reviewed from four aspects: physical modification, chemical modification, biochemical modification, and metal ion coating.
Keywords: Antibacterial property, Surface modification, Three-dimensional printing technology, Titanium alloy
How to cite this article:
Liu H, Cheng X. Research progress on surface modification of three-dimensional printing porous titanium alloys. Digit Med 2023;9:1 |
| Introduction | |  |
Three-dimensional (3D) printing (3DP) technology, also known as additive manufacturing, is a computer-aided technology for stacking and printing real objects layer by layer of 3D models, which can build complex, personalized products with controllable surface shapes and internal structures. Moreover, the mechanical properties of printing materials can be adjusted to better match the needs of multiple uses. 3D printed porous titanium alloy (Ti6-Al4-V) has become an ideal material for orthopedic implants, skull repair, maxillofacial surgery, and dentistry because of its low elastic modulus, good mechanical properties, corrosion resistance, and biocompatibility.[1],[2],[3],[4],[5]The appearance and pore structure of porous Ti6Al4V implants are shown in [Figure 1]. | Figure 1: Appearance and pore structure of the porous Ti6Al4V implants.[14] Copyright 2015, Elsevier BV. (a) Overall appearance of the porous Ti6Al4V implant fabricated using the EBM method. (b) Micro-CT reconstructed 3D image of the porous implant showing the interconnected pore structure. EBM: Electron beam melting, 3D: Three-dimensional.
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Although 3D printed porous titanium alloy can solve the problems of mismatch of elastic modulus of implants and complex bone tissue reconstruction, it is not conducive to rapid bone integration with bone tissue due to its surface biological inertia and lacks other functional properties required by clinical materials. Improve the surface biological characteristics of the material through surface modification treatment to make it have specific biological functions,[6],[7] such as increasing histocompatibility; promoting bone integration;[8],[9] promoting blood vessel growth;[10],[11] endowing the implant with antibacterial activity;[12],[13] reducing the occurrence of implant loosening, postoperative infection, and other related complications; and prolonging the service life of the implant. In this article, the research progress of 3D printing porous titanium alloy surface modification is briefly reviewed. [Table 1] compares the advantages and disadvantages of surface modification of various 3D printing multi titanium alloys reviewed in this paper. | Table 1: Comparison of surface modification methods of three-dimensional printing porous titanium alloy.
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| Physicochemical Surface Modification Of Three-Dimensional Printed Porous Titanium Alloy | | |
Plasma spraying
Plasma spraying technology is a kind of thermal spraying technology with a plasma arc as a heat source. This technology has the advantages of simple operation, fast deposition speed, and easy-to-obtain thick coating.[15] Through plasma spraying, the functional biomolecules are loaded on the surface of titanium alloy to endow the implants with corresponding functions. The preparation of hydroxyapatite (HA) coating by plasma spraying is a traditional method to improve the bone induction ability of titanium alloy materials in the clinic. Huang et al. prepared porous Ti6-Al4-V implants by electron beam melting method and modified the surface with HA by plasma spraying. The results show that the porous Ti6-Al4-V implant with interconnected pores has a high porosity of nearly 70% and a porosity of nearly 500 μmol/L, and plasma-sprayed HA coating can effectively improve bone formation and bone integration.[15] However, the molten particles may produce oxidation during the spraying process, resulting in the deterioration of material properties. Therefore, spraying technology under the protection of vacuum or inert gas has been developed. However, the cost has been increased and the application scenario of plasma spraying has been limited.[16]
Plasma immersion ion implantation
Plasma immersion ion implantation (PIII), combining bioactive trace elements to Ti surface without changing the surface morphology by using pulsed high-pressure ionization of high-purity metal target.[17] PIII can effectively implant functionalized ions into the surface of titanium alloy. It has been reported that Ag, Mg, Zn, Cu, Zr, and Ce[18],[19],[20] have been successfully introduced into Ti implants using this method. The doping content of target ions can be controlled by changing the parameters such as voltage, time, pulse frequency, pulse duration, and arc current. Taking 3D printed porous titanium alloy as the substrate, Zhou et al. implanted Mg2+ into the surface of porous Ti6-Al4-V alloy by PIII. The incorporation of Mg2+ enhanced cell adhesion, diffusion, and proliferation, and improved the in vitro cell compatibility and apatite formation ability of titanium alloy materials.[21] Compared with other chemical methods, PIII is relatively environmentally friendly and simple, and the thermal deformation of samples is usually the smallest. The surface modification of titanium alloys has attracted more and more attention.
Micro-arc oxidation
Micro-arc oxidation (MAO) is an electrochemical surface treatment technology, which has many advantages such as simple process operation, strong machinability, and high production efficiency. When the implant is anodized in the electrolyte at high potential, MAO can discharge the metal on the implant surface and generate a large number of micro/nanoporous structures with high bonding strength in situ.[22] The synthesized oxide coating (usually TiO2) shows excellent biocompatibility, bioactivity, bone integration ability,[23] and the potential to inhibit the release of toxic ions.[24] Zhang et al. reported the successful preparation of anti-infective and osteogenic multifunctional 3D-printed porous Ti6-Al4-V implants via MAO and loaded vancomycin, and the micro/nanoporous structure of MAO could guide protein adsorption and cell adhesion, and further promote the proliferation, migration, and proliferation of osteoblasts.[25] Teng et al. reported the fabrication of surface modification of titanium alloys with interconnected channel structures MAO-CaP-bone morphogenetic protein 2 (BMP2) by using a combination of 3D printing, MAO treatment, and co-precipitation of Ca and players with BMP. The results showed that the BMP2 release from the MAO-CaP-BMP2 group continued for more than 35 days, which was longer than that of Ti without the MAO modification group and without the electrochemical deposition of Ca and P. MAO-CaP-BMP2 modified titanium alloy implants are both osteoinductive and osteoconductive.[10] Although micro-arc oxidation has the advantages of simple operation and low cost, the bonding strength between the structural coating prepared by micro-arc oxidation and the titanium alloy matrix is weak, which is one of the problems to be solved in the future.
Anodic oxidation
Anodic oxidation is also an electrochemical modification method. This technology takes the metal or alloy placed in the electrolyte as the anode and produces an electrochemical reaction under the action of an external electric field to form an oxide layer on the anode surface,[26] and can produce a porous chemically modified surface. Maher et al. combined selective laser melting (SLM) technology, electrochemical anodization, and hydrothermal (HT) process to create a unique double micron to nano-morphology and vertically arranged nano-columnar structure combined with anodization and HT treatment on SLM printed titanium alloy (Ti6-Al4-V) implants. The implants enhanced the deposition of HA-like minerals in simulated body fluid and the adhesion of normal human osteoblast-like cells.[27] Li et al. studied the electrochemical anodization of Ti6-Al4-V to produce nanotubes for the delivery of a novel methylthioadenosine nucleosidase inhibitor. The results showed that an anodized AMTi6-Al4-V nanotube substrate could enhance alkaline phosphatase (ALP) production, bone-specific protein expression, and mineral deposition of human mesenchymal stromal cells.[28] Ren et al. proposed a method that combined ultrasonic acid etching and anodization for surface modification of EBMTi6-Al4-V implants. Nanotube arrays with diameters of 40–50 nm were superimposed on the microstructure substrate by anodization, and the modified titanium alloy had a better promotion effect on the proliferation and differentiation of osteoblasts and the formation of new bone.[29] Constructing micro/nanostructure on the surface of porous titanium alloy by anodic oxidation method to increase the contact area between implant and autologous bone and then improve the integration strength of bone is an effective technical means of titanium alloy modification. In the future, the combination of the anodic oxidation method and other technologies to improve the antibacterial property of porous titanium alloy is the focus of attention.
| Biochemical Surface Modification Of Three-Dimensional Printed Porous Titanium Alloy | | |
Biochemical surface modification methods are mainly to graft biologically active factors such as proteins, polypeptides, and enzymes onto the surface of the material to endow the material with multifunctionality, such as type I collagen, RGD peptide, antimicrobial peptide, and BMP.[30],[31],[32] These active factors directly play the role of bioactive molecules or indirectly induce cell differentiation, and finally promote the osseointegration of titanium implants.
Polypeptides
Polypeptides are synthetic polyamino acids similar in molecular structure to biological polypeptides. Because of their inherent biocompatibility, biodegradability, and bioactivity, peptides have broad application prospects in the surface modification of orthopedic implants. Zhang et al. successfully incorporated a novel DJK-5 peptide onto a porous titanium alloy coating via self-polymerization of dopamine. The modified surface exhibited excellent broad-spectrum antimicrobial efficacy against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa, respectively, and also stimulated osteoblastic responses by promoting cell adhesion and cytoskeletal organization of MC3T3-E1 cells.[33] Zhang et al. designed bioactive peptides of four claw mussel with porous titanium alloy scaffolds: adhesion peptide dopa, anchoring peptide RGD, and osteogenic induction peptide BMP-2. The samples of each group were evaluated in vivo in the rabbit bone defect model. The results show that the bone integration ability of the modified 3D printed porous titanium alloy specimen in vivo is significantly improved, and the bone integration ability of the bifunctional polypeptide coating is the strongest.[34]
Bone morphogenetic protein
Transforming growth factor β (TGF- β), as a member of the bone morphogenetic protein family, can promote the formation of new bone and cartilage, and maintain the growth and dynamic balance of bone tissue.As a member of the family, BMPs can promote the formation of new bone and cartilage and maintain the growth and dynamic balance of bone tissue. Therefore, BMPs are widely used in bone tissue engineering. In the BMP family, BMP-2 is a key bioactive factor. Among many bone tissue growth factors, it is the only one that can induce osteogenesis in vivo.[35] Zhang et al. reported the treatment of cervical spine defects by implanting rhBMP-2-loaded 3D-AVI into male small-tailed Han sheep with cervical spine defects. The experimental results showed that the osseointegration efficiency of the rhBMP-2 group was improved, and rhBMP-2 reduced the activity of the cervical spine. Range and provide a more stable implant.[36] Sun et al. reported the immobilization of BMP-2 on porous titanium surfaces using the cross-linking agent genipin, which improved surface hydrophilicity and protein adsorption, resulting in a noncytotoxic coating with good adhesion properties, which can significantly improve the surface hydrophilicity and protein adsorption and significantly increased cellular mineralization and biological activity.[37]
Chitosan
Chitosan (CH) is the product of removing some acetyl groups from the natural polysaccharide chitin. It is often used as the surface modification coating of titanium alloy implants because of its good biocompatibility, bacteriostasis, immune enhancement, and other physiological functions.[38],[39] CH has good adsorption and biodegradability. It can be used as a drug carrier and play a bioactive role in vivo. The cationic group NH3+ in glucosamine in CH can interact with negatively charged bacteria, destroying the bacterial membrane, to achieve the antibacterial effect. Therefore, it has a wide antibacterial spectrum. Tsai et al. prepared magnesium calcium silicate and CH compounds on Ti6-Al4-V scaffolds. The modified scaffold was able to retain the pore size and its original morphology and structure exhibited mechanical strength comparable to that of natural bone and exhibited hydrophilicity.[40] Li et al. found that CH coating significantly improved diabetes-induced impairment of titanium biological properties through reactive oxygen specie-mediated reactivation of the PI3K/AKT pathway, which provided a new surface functionalization strategy for diabetic patients with titanium implant.[41] Guo and Li used a combination of electron beam melting and freeze-drying to fabricate a novel composite scaffold consisting of porous Ti6-Al4-V moieties filled with CH sponges. Compared with the porous Ti6-Al4-V moieties, the biological response of osteoblasts on the composite scaffold was superior in terms of improved cell attachment, higher proliferation, and good distribution morphology.[42]
| Application Of Metal Ion Coating In Surface Modification Of Three-Dimensional Printed Porous Titanium Alloy | | |
Metal ion coating has a unique application in the surface modification of 3D printed porous titanium alloy. Through surface modification methods such as plasma spraying and micro-arc oxidation, a single or composite coating containing various metals is formed on the surface of titanium alloy, giving titanium alloy corresponding biocompatibility, osteogenic activity, antibacterial, and other properties. This article mainly summarizes the research status of strontium (Sr), zinc, copper, and silver metal ions.
Strontium
Sr is one of the essential trace elements for the human body. As an oleophilic element, Sr increases the number of osteoblasts, stimulates bone formation, and reduces the activity and number of osteoclasts. Sr can also bind to the matrix and accelerate osteoblast maturation and mineralization.[43] Due to the regulation of bone metabolism of Sr, Sr is used alone or in combination to modify the surface coating of materials and improve the osteogenic properties of materials. Wang et al. uniformly manufactured zeolite coatings (SZCs) with Sr ion binding on 3D porous scaffolds using the in situ HT crystal growth method. The experiments showed that SR ion improved apatite formation ability, biocompatibility, corrosion resistance, and ALP activity, and induced new bone formation inside and around porous implants.[44] Wei et al. successfully prepared SR ion functionalized ceramic coating with cortical micro/nano-hierarchical structure on 3D printed titanium by micro-arc oxidation and HT treatment technology.[45]
Zinc
Zinc is an important trace element for the normal growth and development of bones, mainly distributed in the bones, and has the effect of promoting osteogenesis and inhibiting the growth of bacteria. Zinc can promote the osteogenic differentiation of bone marrow mesenchymal stem cells, promote the osteogenesis and mineralization of osteoblasts, and reduce the bone resorption of osteoclasts.[46] In addition, zinc ions change the structure of membrane proteins by binding to microbial cell membrane proteins, resulting in the death of microbial cells.[46] Loading zinc onto the surface of 3D printed porous titanium alloys to improve the osteogenic and antibacterial properties of titanium alloys is a feasible surface modification method. Gao et al. loaded zinc- and silver-containing calcium phosphate coatings onto porous titanium alloy Ti6-Al4-V scaffolds by micro-arc oxidation.[46]
Copper
Copper is an essential element to maintain the normal physiological function of the human body. It can not only inhibit the growth of bacteria but also promote bone formation and neoangiogenesis.[47] MacPherson et al. prepared antibacterial Ti6-Al4-V containing Cu by SLM. The copper-containing alloy only showed certain antibacterial properties, which may be because SLM material is used in the printing state, which contains only a small amount of Ti2Cu.[48] Guo et al. fabricated 3D-printed porous Ti6-Al4-V scaffolds with titanium-copper/titanium-copper nitride (TiCu/Ti-Cu-N) multilayer coatings by arc ion plating. The results indicated that the coating plays an important role in recruiting hBMSCs, upregulating the SDF-1α/CXCR4 axis, p38 expression, and extracellular signal-related kinase and Akt signaling pathways, possibly by recruiting BMSCs and promoting their osteogenic differentiation.[49] Liang et al. developed a 3D porous titanium alloy coating containing 1.92 wt% copper on 3D printed porous Ti6-Al4-V alloy by MAO. The results showed that at this concentration, the antibacterial rate of Cu against S. aureus remained at 100%, while the antibacterial rate against Escherichia coli decreased to 92%.[50]
Silver
Silver ions have the most obvious antibacterial effect among metal ions and have broad-spectrum antibacterial properties. Silver ions can inhibit the proliferation of bacteria by affecting the integrity of the bacterial wall, enzyme activity, and producing large number of reactive oxygen free radicals, resulting in rapid bacterial death.[51] Taking 3D printed porous titanium alloy as the substrate, Jia et al. prepared engineering scaffolds (EBM-MAO/Ag) that can release silver nanoparticles (AGNPS) through a mussel-inspired strategy. The biocompatibility of the modified scaffolds was enhanced and had potential antibacterial properties.[24] Amin Yavari et al. used anodized porous titanium scaffolds to create nanotubes on the entire surface and immersed them in three different concentrations of AgNO3 solutions, and found that the modified 3D printed porous titanium alloys reduced the number of planktonic bacteria and hindered biological. The potency in membrane formation makes it a promising candidate against perioperative implant-related infections.[52]
| Conclusion | | |
3D printed porous titanium and titanium alloy are ideal biomaterials for biomedical bone replacement, and their surface modification has also made some progress. Through plasma spraying, anodizing, micro-arc oxidation, and other surface modification technologies, micro, nanostructure, and HA coatings can be formed on the surface of porous titanium alloy. Micro/nanostructures can significantly increase the surface area of 3D printed porous titanium alloy and promote cell adhesion and proliferation. In addition, the combination of surface modification technology with metal elements and bioactive factors endows the 3D printed porous titanium alloy with pro-osteogenic, anti-inflammatory, vascular, and antibacterial properties, and promotes the long-term stable combination of implants and host bones. However, the complex physiological environment in the human body has high requirements for its performance, and the current surface modification methods cannot fully meet the requirements of clinical application. At the same time, there are some problems in surface modification, such as insufficient bonding strength between coating and substrate, the complex and cumbersome process of preparing composite coating, and so on. Therefore, in the future, many technologies need to be further improved and overcome to meet the clinical needs for a variety of bioactive functions of implants.
Financial support and sponsorship
This research was supported by grants from Changzhou Science and Technology Introduction of Foreign Talents Special Program (CQ20214029).
Conflicts of interest
There are no conflicts of interest.
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[Table 1]
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