Recent clinical data suggest improvement in the fixation of tibia trays for total knee arthroplasty when the trays are additive manufactured with highly porous bone ingrowth structures. Currently, press-fit TKA is less common than press-fit THA. This is partly because the loads on the relatively flat, porous, bony apposition area of a tibial tray are more demanding than those same porous materials surrounding a hip stem. Even the most advanced additive manufactured (AM) highly porous structures have bone ingrowth limitations clinically as aseptic loosening still remains more common in press-fit TKA vs. THA implants.

Osseointegration and antibacterial properties have been shown in vitro and in vivo to improve when implants have modified surfaces that have biomimetic nanostructures designed to mimic and interact with biological structures on the nano-scale. Pre-clinical evaluations show that TiO₂ nanotubes (TNT), produced by anodization, on Ti6Al4V surfaces positively enhance the rate at which osseointegration occurs and TNT nano-texturization enhances the antibacterial properties of the implant surface.²

In this in vivo sheep study, identical Direct Metal laser Sintered (DMLS) highly porous Ti6Al4V specimens with and without TNT surface treatment are compared to sintered bead specimens with plasma sprayed hydroxyapatite-coated surface treatment. Identical DMLS specimens made from CoCrMo were also implanted in sheep tibia bi-cortically (3 per tibia) and in the cancellous bone of the distal femur and proximal tibia (1 per site). Animals were injected with fluorochrome labels at weeks 1, 2 and 3 after surgery to assess the rate of bone integration. The cortical specimens were mechanically tested and processed for PMMA histology and histomorphometry after 4 or 12 weeks. The cancellous samples were also processed for PMMA histology and histomorphometry. The three types of bone labels were visualized under UV light to examine the rate of new bony integration.

At 4 weeks, a 42% increase in average pull-out shear strength between nanotube treated specimens and non-nanotube treated specimens was shown. A 21% increase in average pull-out shear strength between nanotube treated specimens and hydroxyapatite-coated specimens was shown. At 12 weeks, all specimens had statistically similar pull-out values. Bone labels demonstrated new bone formation into the porous domains on the materials as early as 2 weeks.

A separate in vivo study on 8 rabbits infected with methicillin-resistant Staphylococcus aureus showed bacterial colonization reduction on the surface of the implants treated with TNT. In vitro and in vivo evidence suggests that nanoscale surfaces have an antibacterial effect due to surface energy changes that reduce the ability of bacteria to adhere.

These in vivo studies show that TNT on highly porous AM specimens made from Ti6Al4V enhances new bone integration and also reduce microbial attachment.

Periprosthetic infection remains a clinical challenge that may lead to revision surgeries, increased spending, disability, and mortality. The cost for treating hip and knee total joint infections is anticipated to be $1.62 billion by 2020. There is a need for implant surface modifications that simultaneously resist bacterial biofilm formation and adhesion, while promoting periprosthetic bone formation and osseointegration.

In vitro research has shown that nanotextured titanium promotes osteoblast differentiation, and upregulates metabolic markers of osteoblast activity and osteoblast proliferation. In vivo rat studies confirmed increased bone-implant contact area, enhanced de novo bone formation on and adjacent to the implant, and higher pull-out forces compared to non-textured titanium. The authors have advanced a benign electrochemical anodization process based on ammonium fluoride that creates a nanotube surface in as little as 10 minutes (Fig. 1), which can also integrate antibacterial nanosilver (Fig. 2).

The work reported here summarizes in vitro post-inoculation and in vivo post-implantation studies, showing inherent inhibition of methicillin-resistant Staphylococcus aureus (MRSA) by titanium surfaces with nanotubes (TiNT), nanotubes with nanosilver (TiNT+Ag), plain (Ti), and thermal plasma sprayed (TPS) titanium. Ti6Al4V was the base material for all surfaces. In vitro studies evaluated Ti, TPS, four TiNT groups with varying nanotube diameters (60nm, 80nm, 110nm, 150nm), and TiNT+Ag. After seeding with MRSA (10⁵, 10⁶, and 10⁸ CFU/mL), the 110nm diameter nanotubes showed MRSA inhibition up to three-orders of magnitude lower than the Ti and TPS surfaces at 2, 6, and 48 hours.

Following on the in vitro results, New Zealand White rabbits underwent a bilateral implantation of intramedullary tibial implants of the four material groups (4 mm outside diameter; 110nm NT diameter on TiNT and TiNT+Ag implants). One intramedullary canal was inoculated with clinically-derived MRSA (10⁵ CFU in broth) at the time of implantation; one canal had only culture media introduced (control). At a 2-week endpoint, limbs were harvested for analysis, including implant sonication with sonicant bacterial cultured, histology, and microcomputed chromatography. In the sonicant analysis cohort, TPS showed the lowest average MRSA count, while TiNT and TiNT+Ag were the highest. There was one sample each of TPS, TiNT and TiNT+Ag that showed no MRSA. After an additional 24-hour implant incubation, the TiNT and TiNT+Ag samples had no bacteria, but the TPS grew bacteria; therefore, the authors hypothesize that MRSA more readily releases from the TiNT and TiNT+Ag implants during sonication, indicating weaker biofilm adhesion and development. Histologic analysis is currently underway. In a therapeutic experiment, rabbits underwent bilateral implantation, followed by 1 week of infection development, and then 1 week of vancomycin treatment. At the endpoint, implants were sonicated and bacteria was quantified from the sonicant. TiNT showed viable MRSA at only 30% that of TPS-coated levels, while TiNT+Ag implants showed viable MRSA at only 5% that of TPS-coated levels (Fig. 3). These early results indicate that the TiNT and TiNT+Ag surfaces have some inherent antibacterial activity against MRSA, which may increase the efficacy of systemic antibiotic treatments in the setting of periprosthetic joint infections.