Direct comparison of additively manufactured porous titanium and tantalum implants towards in vivo osseointegration.

Material properties of implants such as volume porosity and nanoscale surface modification have been shown to enhance cell-material interactions in vitro and osseointegration in vivo. Porous tantalum (Ta) and titanium (Ti) coatings are widely used for non-cemented implants, which are fabricated using different processing routes. In recent years, some of those implants are being manufactured using additive manufacturing. However, limited knowledge is available on direct comparison of additively manufactured porous Ta and Ti structures towards early stage osseointegration. In this study, we have fabricated porous Ta and Ti6Al4V (Ti64) implants using laser engineered net shaping (LENS™) with similar volume fraction porosity to compare the influence of surface characteristics and material chemistry on in vivo response using a rat distal femur model for 5 and 12 weeks. We have also assessed whether surface modification on Ti64 can elicit similar in vivo response as porous Ta in a rat distal femur model for 5 and 12 weeks. The harvested implants were histologically analyzed for osteoid surface per bone surface. Field emission scanning electron microscopy (FESEM) was done to assess the bone-implant interface. The results presented here indicate comparable performance of porous Ta and surface modified porous Ti64 implants towards early stage osseointegration at 5 weeks post implantation through seamless bone-material interlocking. However, a continued and extended efficacy of porous Ta is found in terms of higher osteoid formation at 12 weeks post-surgery.

Additively manufactured calcium phosphate reinforced CoCrMo alloy: Bio-tribological and biocompatibility evaluation for load-bearing implants.

Cobalt-chromium-molybdenum (CoCrMo) alloys are widely used in load-bearing implants; specifically, in hip, knee, and spinal applications due to their excellent wear resistance. However, due to in vivo corrosion and mechanically assisted corrosion, metal ion release occurs and accounts for poor biocompatibility. Therefore, a significant interest to find an alternative to CoCrMo alloy exists. In the present work we hypothesize that calcium phosphate (CaP) will behave as a solid lubricant in CoCrMo alloy under tribological testing, thereby minimizing wear and metal ion release concerns associated with CoCrMo alloy. CoCrMo-CaP composite coatings were processed using laser engineered net shaping (LENS™) system. After LENS™ processing, CoCrMo alloy was subjected to laser surface melting (LSM) using the same LENS™ set-up. Samples were investigated for microstructural features, phase identification, and biocompatibility. It was found that LSM treated CoCrMo improved wear resistance by 5 times. CoCrMo-CaP composites displayed the formation of a phosphorus-based tribofilm. In vitro cell-material interactions study showed no cytotoxic effect. Sprague-Dawley rat and rabbit in vivo study displayed increased osteoid formation for CoCrMo-CaP composites, up to 2 wt.% CaP. Our results show that careful surface modification treatments can simultaneously improve wear resistance and in vivo biocompatibility of CoCrMo alloy, which can correlate to a reduction of metal ion release in vivo.

Electrically polarized TiO2 nanotubes on Ti implants to enhance early-stage osseointegration.

Ti is characteristically bioinert and is supplemented with modifications in surface topography and chemistry to find use in biomedical applications. The aim of this study is to understand the effects of surface charge on TiO2 nanotubes (TNT) on Ti implants towards early stage osseointegration. We hypothesize that charge storage on TNT will improve bioactivity and enhance early-stage osseointegration in vivo. Commercially pure Ti surface was altered by growing TNT via anodic oxidation followed by the introduction of surface charge through electrothermal polarization to form bioelectret. Our results indicate a stored charge of 37.15 ±â€¯14 mC/cm2 for TNT surfaces. The polarized TNT (TNT-Ps) samples did not show any charge leakage up to 18 months, and improved wettability with a measured contact angle less than 1°. No cellular toxicity through osteoblast proliferation and differentiation in vitro were shown by the TNT-Ps. Enhanced new bone formation at 5 weeks post-implantation for the TNT-Ps in contrast to TNTs was observed in vivo. Histomorphometric analyses show ∼40% increase in mineralized bone formation around the TNT-P implants than the TNTs at 5 weeks, which is indicative of accelerated bone remodeling cycle. These results show that stored surface charge on TiO2 nanotubes helped to accelerate bone healing due to early-stage osseointegration in vivo. STATEMENT OF SIGNIFICANCE: To improve surface bioactivity of metallic biomaterials, various approaches have been proposed and implemented. Among them, stored surface charge has been explored to enhance biological responses for hydroxyapatite ceramics where charged surfaces show favorable bone tissue ingrowth. However, surface charge effects have not yet been explored as a way to mitigate bio-inertness of titanium. This study intends to understand novel integration of bioactive titania-nanotubes and charge storage as surface modification for titanium implants. Our results show excellent biological response due to surface charge on titania-nanotubes offering possibilities of faster healing particularly for patients with compromised bone health.

Calcium phosphate coated 3D printed porous titanium with nanoscale surface modification for orthopedic and dental applications.

This study aims to improve the interfacial bonding between the osseous host tissue and the implant surface through the application of doped calcium phosphate (CaP) coating on 3D printed porous titanium. Porous titanium (Ti) cylinders with 25% volume porosity were fabricated using Laser Engineered Net Shaping (LENS™), a commercial 3D Printing technique. The surface of these 3D printed cylinders was modified by growing TiO2 nanotubes first, followed by a coating of with Sr2+ and Si4+ doped bioactive CaP ceramic in simulated body fluid (SBF). Doped CaP coated implants were hypothesized to show enhanced early stage bone tissue integration. Biological properties of these implants were investigated in vivo using a rat distal femur model after 4 and 10 weeks. CaP coated porous Ti implants have enhanced tissue ingrowth as was evident from the CT scan analysis, push out test results, and the histological analysis compared to porous implants with or without surface modification via titania nanotubes. Increased osteoid-like new bone formation and accelerated mineralization was revealed inside the CaP coated porous implants. It is envisioned that such an approach of adding a bioactive doped CaP layer on porous Ti surface can reduce healing time by enhancing early stage osseointegration in vivo.

Silver nanoparticle deposited implants to treat osteomyelitis.

In this study, electrolytically deposited strongly adherent silver nanoparticles on stainless-steel (SS) implants were used for in situ osteomyelitis treatment. Samples were heat treated to enhance adhesion of silver on 316 L SS. Ex vivo studies were performed to measure silver-release profiles from the 316 L SS screws inserted in equine cadaver bones. No change in the release profiles of silver ions were observed in vitro between the implanted screws and the control. In vivo studies were performed using osteomyelitic rabbit model with 3 mm diameter silver-deposited 316 L SS pins at two different doses of silver: high and low. Infection control ability of the pins for treating osteomyelitis in a rabbit model was measured using bacteriologic, radiographic, histological, and scanning electron microscopic studies. Silver-coated pins, especially high dose, offered a promising result to treat infection in animal osteomyelitis model without any toxicity to major organs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1073-1083, 2018.

Understanding long-term silver release from surface modified porous titanium implants.

Prevention of orthopedic device related infection (ODRI) using antibiotics has met with limited amount of success and is still a big concern during post-surgery. As an alternative, use of silver as an antibiotic treatment to prevent surgical infections is being used due to the well-established antimicrobial properties of silver. However, in most cases silver is used in particulate form with wound dressings or with short-term devices such as catheters but not with load-bearing implants. We hypothesize that strongly adherent silver to load-bearing implants can offer longer term solution to infection in vivo. Keeping that in mind, the focus of this study was to understand the long term release study of silver ions for a period of minimum 6months from silver coated surface modified porous titanium implants. Implants were fabricated using a LENS™ system, a powder based additive manufacturing technique, with at least 25% volume porosity, with and without TiO2 nanotubes in phosphate buffer saline (pH 7.4) to see if the total release of silver ions is within the toxic limit for human cells. Considering the fact that infection sites may reduce the local pH, silver release was also studied in acetate buffer (pH 5.0) for a period of 4weeks. Along with that, the osseointegrative properties as well as cytotoxicity of porous titanium implants were assessed in vivo for a period of 12weeks using a rat distal femur model. In vivo results indicate that porous titanium implants with silver coating show comparable, if not better, biocompatibility and bonding at the bone-implant interface negating any concerns related to toxicity related to silver to normal cells. The current research is based on our recently patented technology, however focused on understanding longer-term silver release to mitigate infection related problems in load-bearing implants that can even arise several months after the surgery. STATEMENT OF SIGNIFICANCE: Prevention of orthopedic device related infection using antibiotics has met with limited success and is still a big concern during post-surgery. Use of silver as an antibiotic treatment to prevent surgical infections is being explored due to the well-established antimicrobial properties of silver. However, in most cases silver is used in particulate form with wound dressings or with short-term devices such as catheters but not with load-bearing implants. We hypothesize that strongly adherent silver to load-bearing implants can offer longer-term solution towards infection in vivo. Keeping that in mind, the focus of this study was to understand the long-term release of silver ions, for a period of minimum 6months, from silver coated surface modified porous titanium implants.

In Vivo Response of Laser Processed Porous Titanium Implants for Load-Bearing Implants.

Applications of porous metallic implants to enhance osseointegration of load-bearing implants are increasing. In this work, porous titanium implants, with 25 vol.% porosity, were manufactured using Laser Engineered Net Shaping (LENS™) to measure the influence of porosity towards bone tissue integration in vivo. Surfaces of the LENS™ processed porous Ti implants were further modified with TiO2 nanotubes to improve cytocompatibility of these implants. We hypothesized that interconnected porosity created via additive manufacturing will enhance bone tissue integration in vivo. To test our hypothesis, in vivo experiments using a distal femur model of male Sprague-Dawley rats were performed for a period of 4 and 10 weeks. In vivo samples were characterized via micro-computed tomography (CT), histological imaging, scanning electron microscopy, and mechanical push-out tests. Our results indicate that porosity played an important role to establish early stage osseointegration forming strong interfacial bonding between the porous implants and the surrounding tissue, with or without surface modification, compared to dense Ti implants used as a control.

Mechanical degradation of TiO2 nanotubes with and without nanoparticulate silver coating.

The primary objective of this research was to evaluate the extent of mechanical degradation on TiO2 nanotubes on Ti with and without nano-particulate silver coating using two different lengths of TiO2 nanotubes-300nm and ~1µm, which were fabricated on commercially pure Titanium (cp-Ti) rods using anodization method using two different electrolytic mediums-(1) deionized (DI) water with 1% HF, and (2) ethylene glycol with 1% HF, 0.5wt% NH4F and 10% DI water. Nanotubes fabricated rods were implanted into equine cadaver bone to evaluate mechanical damage at the surface. Silver was electrochemically deposited on these nanotubes and using a release study, silver ion concentrations were measured before and after implantation, followed by surface characterization using a Field Emission Scanning Electron Microscope (FESEM). In vitro cell-material interaction study was performed using human fetal osteoblast cells (hFOB) to understand the effect of silver coating using an MTT assay for proliferation and to determine any cytotoxic effect on the cells and to study its biocompatibility. No significant damage due to implantation was observed for nanotubes up to ~1µm length under current experimental conditions. Cell-materials interaction showed no cytotoxic effects on the cells due to silver coating and anodization of samples.