J.J. Krygier's research while affiliated with McGill University and other places

An Osteonecrosis Intervention Implant made of porous tantalum was recently developed to provide structural support and a compatible surface for tissue ingrowth in osteonecrotic femoral heads. From an investigational device exemption study that comprised 113 implants, we carried out a retrieval analysis of clinically failed implants. Seventeen porous tantalum implants that had been used for the treatment of Steinberg stage-II osteonecrosis of the hip were retrieved at the time of conversion to a total hip arthroplasty. Fifteen implants that had been transected near the base of the femoral neck with the proximal portion left in situ within the femoral head underwent histopathologic analysis at an average of 13.4 months (range, three to thirty-six months) after implantation. Residual osteonecrosis was present in fourteen of the fifteen specimens. Fracture of the subchondral bone of the femoral head was present in all instances, and collapse of the femoral head was present in nine instances (60%). Backscattered scanning electron microscopy confirmed the presence of bone ingrowth in thirteen (87%) of the fifteen specimens. The mean extent of bone ingrowth was 1.9% (range, 0% to 4.4%). The retrieved implants were associated with little bone ingrowth and insufficient mechanical support of subchondral bone. The implant design, the surgical technique, its application, and the clinical characteristics of candidates for this procedure should continue to be monitored closely.

The purpose of this study was to characterize a technique to effectively mask surface chemistry without modifying surface topography. A thin layer of titanium was deposited by physical vapor deposition (PVD) onto different biomaterial surfaces. Commercially pure titanium disks were equally divided into three groups. Disks were either polished to a mirror finish, grit blasted with alumina particles, or grit blasted and subsequently plasma sprayed with a commercial grade of hydroxyapatite (HA). A subgroup of each of these treatment types was further treated by masking the entire disk surface with a thin layer of commercially pure titanium deposited by PVD. A comparison of surface topography and chemical composition was carried out between disks within each treatment group. Canine marrow cells were seeded on all disk surfaces to determine the stability of the PVD Ti mask under culture conditions. The PVD process did not significantly alter the surface topography of any samples. The thin titanium layer completely masked the underlying chemistry of the plasma sprayed HA surface and the chemistry of the plasma vapor deposited titanium layer did not differ from that of the commercially pure titanium disks. Aliquots obtained from the media during culture did not indicate any significant differences in Ti concentration amongst the Ti and Ti-masked surfaces. The PVD application of a Ti layer on HA coatings formed a stable, durable, and homogenous layer that effectively masked the underlying surface chemistry without altering the surface topography.

The bisphosphonate zoledronic acid chemically and physically was bound to hydroxyapatite-coated porous tantalum implants. The zoledronic acid elution characteristics in saline were determined as a function of time and the in vivo effects of elution were quantified at 12 weeks in a canine ulnar implant model. Intramedullary implants surgically were implanted bilaterally into the ulnae of a control group of five dogs and a zoledronic acid-dosed (0.05 mg zoledronic acid) group of four dogs. Computerized image analysis of undecalcified histologic sections was used to quantify the amount of peri-implant bone within the intramedullary canal, the percentage of available pore space filled with new bone, and the number and size of the individual bone islands within the implant pores. The data were analyzed using a hierarchical analysis of variance with 95% confidence intervals. The peri-implant bone occupied a mean of 13.8% of the canal space in controls and 32.2% of the canal space in zoledronic acid-dosed dogs, a relative difference of 134% (2.34-fold) that was significant. The mean extent of bone ingrowth was 12.5% for the control implants and 19.8% for the zoledronic acid-dosed dogs, a relative difference of 58% that was statistically significant. Individual islands of new bone formation with the implant pores were similar in number in both implant groups but were 71% larger on average in the ZA-dosed group. We are the first authors to show that local elution of a bisphosphonate can cause substantial bone augmentation around and within porous orthopaedic implants. The concept represents a potential tool for restoration of bone stock and enhancement of implant fixation in primary and revision cementless joint arthroplasty surgeries in the face of compromised or deficient bone.

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone.

Various porous coatings—most notably, those manufactured by the sintering of cobalt-chrome or titanium beads and the diffusion bonding of titanium fiber wires—have been utilized for the biologic attachment of orthopaedic implants during the past three decades1. About ten years ago, a novel porous biomaterial made from commercially pure tantalum2-5 with a unique set of physical and mechanical properties was developed. Compared with conventional porous coatings, this material possesses higher volume porosity, more freely communicating pores, a higher coefficient of friction against bone, and a lower bulk stiffness (Fig. 1). In addition, the material is structural in that it has sufficient strength to enable the manufacture of implants without the need for a supportive solid metal substrate. Fig. 1 Top, Scanning electron micrograph illustrating the three-dimensional, open-pored structure of the porous tantalum biomaterial. The inset highlights the slight microtexture on the tantalum struts that results from the manufacturing process. Bottom, Monoblock cups manufactured by partial infiltration of polyethylene into the porous tantalum shell by direct compression-molding. Previous studies have characterized the physical and mechanical properties of porous tantalum6,7. Histologic analyses of the bone and fibrous ingrowth responses to various implants in animals have indicated a propensity for rapid infiltration of porous tantalum with healing tissue and relatively rapid rates of mechanical attachment8-14. Recent cell-culture studies have characterized the osteoblastic response to commercially pure tantalum, adding further confirmation to its long history as a biocompatible elemental metal2-5,15. Porous tantalum has been utilized for a wide variety of clinical applications since 1997, including joint replacement, reconstruction following tumor resection, the treatment of avascular necrosis of the femoral head, and spine fusion. The purpose of the present study was to document the clinical results obtained with porous …

We designed an in vivo study to determine if the superimposition of a microtexture on the surface of sintered titanium beads affected the extent of bone ingrowth. Cylindrical titanium intramedullary implants were coated with titanium beads to form a porous finish using commercial sintering techniques. A control group of implants was left in the as-sintered condition. The test group was etched in a boiling acidic solution to create an irregular surface over the entire porous coating. Six experimental dogs underwent simultaneous bilateral femoral intramedullary implantation of a control implant and an acid etched implant. At 12 weeks, the implants were harvested in situ and the femora processed for undecalcified, histological examination. Eight transverse serial sections for each implant were analysed by backscattered electron microscopy and the extent of bone ingrowth was quantified by computer-aided image analysis. The extent of bone ingrowth into the control implants was 15.8% while the extent of bone ingrowth into the etched implants was 25.3%, a difference of 60% that was statistically significant. These results are consistent with other research that documents the positive effect of microtextured surfaces on bone formation at an implant surface. The acid etching process developed for this study represents a simple method for enhancing the potential of commonly available porous coatings for biological fixation.

There has been a revived interest in metal-metal total hip replacements because of their potential for improved wear performance compared with conventional metal-polyethylene implants. The aim of the present study was to characterize metal wear particles isolated from metal-metal hip simulator testing of various clinically relevant alloys and to analyze the effects of these alloys and the number of loading cycles on wear particle characteristics. Implants were manufactured using medical-grade cobalt-chromium-molybdenum (CoCrMo) alloys that were high-carbon wrought, low-carbon wrought, or cast (with solution annealing). Testing was performed in a MATCO orbital bearing hip simulator in 95% bovine calf serum. The wear particles were isolated from the serum at test periods of 0-0.25 million cycles (Mc) (run-in wear) and 1.75-2 Mc (steady-state wear) using an enzymatic protocol previously optimized to minimize particle changes due to reagents. Isolated particles embedded in epoxy resin were characterized by transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDXA). The EDXA results revealed the predominance of "lighter" particles containing Cr and O (most likely chromium oxide particles from the passivation layer) and fewer darker CoCrMo particles, with varying ratios of Co and Cr (possibly from carbides and from implant matrix material). More CoCrMo particles were observed with the low-carbon wrought alloy, but the majority of the particles for all three alloys was chromium oxides, especially for the 1.75-2 Mc test period. Image analysis of TEM micrographs revealed that for 0-0.25 Mc, there was up to 21% needle-shaped particles but that the majority remained round to oval in shape, reflecting the predominance of chromium oxide particles. Particle length averaged about 52 +/- 4 nm, with only small differences due to the alloy. For 1.75-2 Mc, most particles were round to oval in shape. They were even less needle-shaped than at 0.25 Mc, and they had a slightly smaller length, averaging 46 +/- 3 nm. In addition to characterizing the size and shape of particles from a MATCO simulator, this study is the first to demonstrate that particles that do not contain Co (presumably chromium oxides) can be predominant in the wear of metal-metal hip implants. It is therefore recommended that future in vitro and in vivo studies include the effects of these particles rather than just the effects of CoCrMo particles on the overall tissue response.

The purpose of the current study was to ascertain the relative contributions of surface chemistry and topography to the osseointegration of hydroxyapatite-coated implants. A canine femoral intramedullary implant model was used to compare the osseous response to commercially pure titanium implants that were either polished, grit-blasted, plasma-sprayed with hydroxyapatite, or plasma-sprayed with hydroxyapatite and masked with a very thin layer of titanium using physical vapor deposition (titanium mask). The titanium mask isolated the chemistry of the underlying hydroxyapatite layer without functionally changing its surface topography and morphologic features. At 12 weeks, the bone-implant specimens were prepared for undecalcified thin section histologic evaluation and serial transverse sections were quantified with backscattered scanning electron microscopy for the percentage of bone apposition to the implant surface. Bone apposition averaged 3% for the polished implants and 23% for the grit-blasted implants. Bone apposition to the hydroxyapatite-coated implants averaged 74% whereas bone apposition to the titanium mask implants averaged 59%. Although there was significantly greater osseointegration with the hydroxyapatite-coated implants, 80% of the maximum bone forming response to the implant surfaces developed with the titanium mask implants. This simple, controlled experiment revealed that topography is the dominant factor governing bone apposition to hydroxyapatite-coated implants.

Theory, supported by some experimental evidence, suggests that metal-on-metal (m-m) hip implants can have protective elastohydrodynamic lubrication films during continuous walking that may reduce wear. A simple transient model indicated that such films were remarkably constant during continuous motion and could prevent surface contact of smooth, low clearance implants. However, these films could both form and breakdown rapidly during intermittent motion in vivo. Thus, a more representative simulator motion protocol was specified involving repeated cycles of Stopping, dwelling with a constant load for 1 minute and starting 10 minute sessions that applied continuous walking conditions. An automatic control system was designed and to implement this protocol in a hip simulator. Six implants were tested for about 3 million cycles (Mc) under the developed stop-dwell-start motion protocol. Compared with continuous motion testing of similar implants, the wear at 3 Mc approximately doubled (from about 0.6 to 1.2 mm3) and wear rates showed considerable increase (from 0.04 to 0.19 mm3/Mc). The simulator wear of m-m hip implants should be investigated during intermittent as well as continuous motions. Ultimately, designs should address the issue of wear during stop-dwell-start motion protocols.