Advanced Surface Modification for 3D-Printed Titanium Alloy Implant Interface Functionalization

Abstract

With the development of three-dimensional (3D) printed technology, 3D printed alloy implants, especially titanium alloy, play a critical role in biomedical fields such as orthopedics and dentistry. However, untreated titanium alloy implants always possess a bioinert surface that prevents the interface osseointegration, which is necessary to perform surface modification to enhance its biological functions. In this article, we discuss the principles and processes of chemical, physical, and biological surface modification technologies on 3D printed titanium alloy implants in detail. Furthermore, the challenges on antibacterial, osteogenesis, and mechanical properties of 3D-printed titanium alloy implants by surface modification are summarized. Future research studies, including the combination of multiple modification technologies or the coordination of the structure and composition of the composite coating are also present. This review provides leading-edge functionalization strategies of the 3D printed titanium alloy implants.

Keywords: 3D-printed; implant interface; surface functionalization; surface modication; titanium alloy.

FIGURE 1

3D-printing of titanium alloy process diagram (A) 3D-printed customized implant data acquisition process (Sing et al., 2016). (B) Process chain for preparing orthopedic implants by 3D-printed technology (Sing et al., 2016). (C) Schematic diagram of powder bed process (Wang et al., 2017). (D) Lens process schematic diagram (Antolak-Dudka et al., 2019).

FIGURE 2

Schematic diagram of chemical, physical, and biological surface modification technologies. (A) Implant surface microstructure produced by electrophoretic deposition (Surmeneva et al., 2019). (B) Microstructure of implant surface produced by laser peening (Soyama and Takeo, 2020). (C) Surface microstructures of implants produced by hydrogel packaging (Mieszkowska et al., 2020).

FIGURE 3

LBL vancomycin and BMP-2-coated implants (Amin Yavari et al., 2020). (A) Schematic illustration of the layer-by-layer coating process. (B) The biocompatibility of the scaffold was analyzed 8 weeks after implantation, the porous Ti structures did not induce an adverse tissue response in any of the groups, shown by the absence of acute inflammation or fibrous encapsulation at the material-tissue interface. In the case of any LBL remnants, no acute inflammatory response was seen around the polymer. At the same time, we observed a high density of blood vessel formation. (C) Representative images of planktonic and adherent bacteria on the surfaces of different experimental groups. In the experimental group containing vancomycin, the number of bacteria was significantly less. (D) In the live death staining experiment, the surface of the implant was completely covered by living cells, and the surface coating had no inhibitory effect on cell adhesion and proliferation.

FIGURE 4

Ti6Al4V alloy/GelMA hybrid implant with dual bionic features (GMPT) for bone defect repair (Ma et al., 2021). (A) Schematic illustrations of the biomimetic GMPT with dual-bionic features. (B) In situ implantation of PT and GMPT implants, micro-CT 3D reconstruction of PT and GMPT in critical radius defects of rabbits. The implants in GMPT group had higher osteogenic activity than uncoated implants, and the osteogenic ability of the 10% GMPT group was the strongest. (C) The fabrication process and characterization of GMPT. (D) Histological analysis of implant samples after 4 and 12 weeks in rabbit radius defect sites. The GMPT group showed thicker and higher number of trabeculae than the PT group at both weeks 4 and 12 (yellow arrows indicate the PT implant, white arrows indicate new bone, and green arrows reveal new vessels). The 10% GMPT group showed the best osteogenesis and angiogenesis ability.

FIGURE 5

Ag⁺ coating of nanotubes prepared by anodic oxidation (Amin Yavari et al., 2016). (A) Schematic diagram of 3D-printed titanium alloy surface covered with nanotubes and carrying Ag⁺ to inhibit bacterial growth. (B) The inhibitory effect of different concentrations of Ag⁺ loaded on the implant surface on cell proliferation and adhesion. (C) SEM images of anodized porous titanium with the following parameters: 20 V, 3 h; 30 V, 2 h; 40 V, 3 h. (D) Antibacterial performance of AsM, NT, NT-0.02 Ag⁺, NT-0.1 Ag⁺, and NT-0.5 Ag⁺ against Staphylococcus aureus after 7 days. The first row corresponds to planktonic bacteria and the second row to adherent bacteria; the group with higher Ag⁺concentration had obvious antibacterial ability than the group with lower Ag⁺ concentration.

FIGURE 6

A 3D-printed titanium cage combined with a drug-releasing system for in situ drug release and bactericidal action (Li Y et al., 2020). (A) The schematic illustration of a 3D-printed titanium cage coated with PVA-vancomycin for preventing surgical site infections (Berbel, Banczek et al.) after spine surgery. (B) Antibacterial evaluation of Ti-VH@PVA cages in vitro. The obvious bacteriostatic circle was observed with regard to Staphylococcus aureus and Staphylococcus epidermidis. (C) Evaluation of Ti-VH@PVA cages for preventing SSIs in vivo. With the extension of time, the infiltration of inflammatory cells decreased significantly in Ti-VH@PVA cage. Furthermore, the thickness of the discontinuous fibrous capsule between the trabecular bone and the Ti-VH@PVA cage increased. This indicates that Ti-VH@PVA cage has a significant inhibitory effect on Staphylococcus aureus.

FIGURE 7

Osteogenic exosomes induce osteogenic differentiation (Zhai et al., 2020). (A) The schematic illustration of cell-free bone tissue regeneration by the stem cell-derived exosomes. (B) The characterization of the stem cell-derived exosomes. a) AFM and b) TEM showing the size and morphology of the exosomes derived from hMSCs. Scale bar: 200 nm. c) The size and concentration of the hMSCs-derived exosomes by the NanosightNS300. The inset is an image showing the snapshot of video tracking. d) The western blot analysis of the exosome derived from the pre-differentiated hMSCs and hMSCs. (C) Osteogenic differentiation of hMSCs by the osteogenic exosomes a) Immunofluorescence staining of osteogenic markers (COL-1, OPN) in hMSCs induced by osteogenic exosomes. b) Immunofluorescence staining of osteogenic markers (COL-1, OPN) in hMSCs induced by osteogenic medium. There was no significant difference between osteogenic exosomes treatment and osteogenic medium treatment, which proved the osteogenic induction function of osteogenic exosomes.

FIGURE 8

Effect of UNSM treatment on 3D-printed NiTi alloy surface (Ma et al., 2017). (A) Schematic of the UNSM processing showing its effect on surface finish, subsurface porosity, and surface hardening. (B) Wear scars of untreated (a and b) samples and UNSM-treated (c and d) samples at 6,000 (a and c) and 24,000 (b and d) cycles. (C) Porosity distribution on the untreated surface and UNSM-treated surface. (D) a) Appearance of the AM NiTi samples before and after UNSM treatment; b) and c) show the optical images of the non-treated sample. d) and e) show the optical images of the UNSM-treated sample. The treated samples have better wear resistance and lower porosity than untreated samples.

SCHEME 1

Surface modification technologies and biological functionalization of 3D-printed titanium alloy implants.