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Joshua J Jacobs

Publications and source records attributed to Joshua J Jacobs.

49 records · Page 3Linked to original sources

Interfacial kinetics of titanium- and cobalt-based implant alloys in human serum: metal release and biofilm formation.

The biocompatibility of metallic implant surfaces is governed in large part by the interfacial kinetics associated with metal release and protein binding. The kinetics of metal release from, and protein binding to, cobalt- and titanium-based implant alloys in human serum were investigated by (1). measuring the temporal release of Cr and Ti into serum from Co-Cr-Mo (ASTM F-75) and Ti implant alloys (Ti-6Al-4V: ASTM F136, and commercially pure Ti, cpTi: ASTM F67), respectively; (2). examining the composition of human serum proteins adsorbed onto the surfaces of Co- and Ti-based implant alloys; and (3). identifying the serum proteins associated with the binding of soluble Cr and Ti degradation products. Analysis of metal dissolution kinetics found that Cr was released from Co-based implant alloy at an order of magnitude higher than Ti was released from Ti-based implant alloys. Serum became saturated with soluble CR and Ti at levels as high as 3250 ng/mL Ti from cpTi; 3750 ng/mL Ti from Ti-6Al-4V; and 35400 ng/mL Cr from Co-Cr-Mo degradation. The observation that human serum binds more released metal from Co-based alloy dissolution was consistent with the observed differences in biofilm composition between the two alloys, where additional serum protein(s) of approximately approximately 140 (kDa) molecular weight were detected on Co-based implant alloy surfaces. However, both Cr and Ti released from Co- and Ti-based alloys exhibited a bimodal binding pattern to both low molecular weight serum protein(s) (<32 kDa), and to higher molecular weight protein(s) in the 180-250 kDa range. Identification of metal alloy-dependent biofilm compositions and dissolution products provides the basis for understanding the bioavailability and bioreactivity of these implant alloys and their degradation products.

Alloys↗

Metal degradation products: a cause for concern in metal-metal bearings?

In the majority of patients, orthopaedic implants are biocompatible. However, there is an increasing recognition that, in the long-term, permanent orthopaedic implants may be associated with adverse local and remote tissue responses in some individuals. These adverse effects are mediated by the degradation products of implant materials. The recent reintroduction of metal-on-metal bearings for total hip arthroplasty has heightened concerns about the biologic response to metal degradation products in light of the fact that the serum and urine metal concentrations in patients with these implants typically are higher than those seen in patients with conventional metal-on-polyethylene bearings. From previous studies of long-term metal-on-metal McKee-Farrar implants, it seems that these elevated levels may persist for the duration of the implant's lifetime. This is of particular concern in the younger and more active patient in whom life expectancy after implantation may exceed 30 years. The association of metal release from orthopaedic implants with any metabolic, bacteriologic, immunologic, or carcinogenic toxicity currently remains conjectural because cause and effect have not been established in human subjects. However, continued surveillance of patient populations with metal implants, particularly those with metal-metal bearings, is warranted.

Foreign Bodies↗

Extended trochanteric osteotomy in complex primary total hip arthroplasty. A brief note.

BACKGROUND: The extended trochanteric osteotomy has been a useful approach for patients undergoing revision total hip arthroplasty; however, it has not been well described as an approach for those undergoing complex primary total hip arthroplasty. The purpose of the present report is to describe our experience with the use of an extended trochanteric osteotomy for patients undergoing complex primary total hip arthroplasty. METHODS: Six patients underwent primary total hip arthroplasty with use of an extended trochanteric osteotomy. The reasons for the use of this technique included severe femoral deformity, removal of intraosseous hardware, and high-riding developmental hip dysplasia. A fully porous-coated femoral component with diaphyseal fixation was used for all reconstructions. The mean age of the patients at the time of surgery was fifty-six years. Clinical and radiographic evaluation was performed at a minimum of two years. RESULTS: After a mean duration of follow-up of fifty months, all patients had an osseointegrated, stable femoral component. The site of the extended trochanteric osteotomy healed in five of the six patients. One patient had nonunion at the osteotomy site and a fracture at the base of the greater trochanter, with a subsequent fracture of the femoral component. The mean Merle D'Aubigné and Postel pain and walking scores improved from 2.2 and 2.3 preoperatively to 5.3 and 4.7 at the time of the final follow-up (p < 0.001). CONCLUSIONS: The extended trochanteric osteotomy is useful for the correction of femoral deformity and facilitates the removal of intraosseous hardware in carefully selected patients undergoing complex primary total hip arthroplasty.

Adult↗

Concentration- and composition-dependent effects of metal ions on human MG-63 osteoblasts.

Metal debris from implants has been shown to alter the function of osteoblasts in cell cultures. Its remains unclear, however, if specific forms of released ionic metals are involved in the pathogenesis of periprosthetic osteolysis. We evaluated the relative effects of ionic forms of implant metals by treating human osteoblast-like MG-63 osteosarcoma cells with eight concentrations (0.001-10.0 mM) of Cr(+3), Mo(+5), Al(+3), Ta(+5), Co(+2), Ni(+2), Fe(+3), Cu(+2), Mn(+2), Mg(+2), Na(+2), and V(+3) chloride solutions. The results demonstrated that the metal ions differentially affected osteoblast proliferation, viability, type-I collagen gene expression, and cytokine release. The metal ions were ranked in order from least to most toxic (based on a 50% reduction in viability) as follows: Na < Cr < Mg < Mo < Al < Ta < Co < Ni < Fe < Cu < Mn < V. Metal-induced decreases in osteoblast proliferation were similar in ranking. Nontoxic concentrations of metals had no effect on procollagen alpha1[I] gene expression; only at toxic concentrations did metals produce a decrease in gene expression. The most toxic metals (V, Mn, Fe, and Ni) were also the only metals found to induce IL-6 secretion on a per cell basis (of the cytokines tested, interleukin 6 (IL-6), interleukin beta 1 (IL-1beta), transforming growth factor beta 1 (TGF-beta1), and tumor necrosis factor alpha (TNF-alpha), only IL-6 was detectable in the culture medium after 48 h for any metal at any concentration). Less toxic metals (e.g., Co and Cr) had little effect on IL-6 release, even at high concentrations. In general, metal ions reduced osteoblast function (i.e., proliferation and collagen gene expression) in proportion to the degree of toxicity. These results support the hypothesis that adverse local cellular responses (particularly necrotic responses) associated with metal debris from implanted metallic devices may be due in part to metal ions released from implants or from particulate debris.

Blotting, Northern↗

Shedding of the interleukin-6 (IL-6) receptor (gp80) determines the ability of IL-6 to induce gp130 phosphorylation in human osteoblasts.

Human osteoblasts produce interleukin-6 (IL-6) and respond to IL-6 in the presence of soluble IL-6 receptor (sIL-6R), but the cell surface expression of IL-6R and the mechanism of sIL-6R production are largely unknown. Three different human osteoblast-like cell lines (MG-63, HOS, and SaOS-2) and bone marrow-derived primary human osteoblasts expressed both IL-6R and gp130 as determined by flow cytometry and immunoprecipitation. However, the membrane-bound IL-6R was nonfunctional, as significant tyrosine phosphorylation of gp130 did not occur in the presence of IL-6. Phorbol myristate acetate induced a dramatic increase of both IL-6R shedding (i.e. the production of sIL-6R) and IL-6 release in osteoblast cultures, but the cell surface expression of gp130 remained unchanged. IL-6 complexed with sIL-6R, either exogenously introduced or derived from the nonfunctional cell surface form by shedding, induced rapid tyrosine phosphorylation of gp130. This effect was inhibited by neutralizing antibodies to either sIL-6R or gp130, indicating that the gp130 activation was induced by IL-6/sIL-6R/gp130 interaction. Protein kinase C inhibitors blocked phorbol myristate acetate-induced and spontaneous shedding of IL-6R resulting in the absence of sIL-6R in the culture medium, which in turn also prevented the activation of gp130. In conclusion, human osteoblasts express cell surface IL-6R, which is unable to transmit IL-6-induced signals until it is shed into its soluble form. This unique mechanism provides the flexibility for osteoblasts to control their own responsiveness to IL-6 via the activation of an IL-6R sheddase, resulting in an immediate production of functionally active osteoblast-derived sIL-6R.

Antigens, CD↗

Titanium particles induce the immediate early stress responsive chemokines IL-8 and MCP-1 in osteoblasts.

Exposure of human osteoblasts to ultrafine titanium (Ti) particles has been shown to alter osteoblast gene expression. We previously reported that Ti particles can increase IL-6 release and suppress the gene expression of procollagens alpha1[I] and alpha1[III] in human osteoblasts. In this study, we now demonstrate that Ti particles can rapidly induce the chemotactic cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), two immediate early stress responsive chemokines important for the activation and chemotaxis of neutrophils and macrophages, respectively. In MG-63 osteosarcoma cells and bone marrow derived primary osteoblasts Ti particles selectively increased the steady state levels of IL-8 and MCP-1 mRNA in a time and concentration dependent manner. The increased chemokine mRNA correlated with increased secretion of IL-8 and MCP-1 protein. Actinomycin D, a potent RNA polymerase II inhibitor, blocked the Ti particle induction of IL-8 and MCP-1 mRNA expression, whereas cycloheximide, which inhibits protein synthesis, failed to inhibit chemokine gene expression suggesting Ti particles directly target activation of chemokine gene transcription. Consistent with a transcriptional mechanism not involving new protein synthesis, we demonstrate that Ti particles induce the binding of the p65 and p50 subunits of the latent transcription factor NF-kappaB to the IL-8 gene promoter. Taken together, these data demonstrate that Ti particles can activate transcription of the stress responsive chemokine genes IL-8 and MCP-1 in human osteoblasts.

Chemokine CCL2↗

Serum and urine metal levels in patients with metal-on-metal surface arthroplasty.

The resurgence of metal-on-metal articulating surfaces for hip arthroplasty has also heightened concerns about the degree and magnitude of metal particle generation and the accompanying increase in circulating metal ion concentrations. In this study, we measured the concentration of chromium in serum and urine and the concentration of cobalt in serum in twenty-five patients with modern metal-on-metal surface arthroplasty of the hip in a prospective manner. The results showed that the mean post-operative chromium in serum levels were 22-fold, 23-fold and 21-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative cobalt in serum levels were 8-fold, 7-fold and 6-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative chromium in urine levels were 9-fold, 10-fold and 14-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The values seen in this study with the current generation of surface arthroplasties are: (a) lower than those seen in an earlier generation of surface arthroplasties; (b) in the same range as those observed in association with metal-on-metal conventional total hip replacements, which typically have smaller head sizes; (c) higher than values observed in patients with conventional metal-on-polyethylene articulating couples.

Journal Article↗

A multicenter retrieval study of the taper interfaces of modular hip prostheses.

A multicenter retrieval analysis of 231 modular hip implants was done to investigate the effects of material combination, metallurgic condition, flexural rigidity, head and neck moment arm, neck length, and implantation time on corrosion and fretting of modular taper surfaces. Scores for corrosion and fretting were assigned to medial, lateral, anterior, and posterior quadrants of the necks, and proximal and distal regions of the heads. Neck and head corrosion and fretting scores were found to be significantly higher for mixed alloy versus similar alloy couples. Moderate to severe corrosion was observed in 28% of the heads of similar alloy couples and 42% of the heads of mixed alloy couples. Differences in corrosion scores were observed between components made from the same base alloy, but of different metallurgic conditions. Corrosion and fretting scores tended to be higher for heads than necks. Implantation time and flexural rigidity of the neck were predictors of head and neck corrosion and head fretting. The results of this study suggest that in vivo corrosion of modular hip taper interfaces is attributable to a mechanically-assisted crevice corrosion process. Larger diameter necks will increase neck stiffness and may reduce fretting and subsequent corrosion of the taper interface regardless of the alloy used. Increasing neck diameter must be balanced, however, with the resulting loss of range of motion and joint stability.

Adult↗

Coventry Award paper. Backsurface wear and deformation in polyethylene tibial inserts retrieved postmortem.

Wear and deformation were characterized at the backsurface of 25 posterior cruciate-retaining total knee arthroplasty polyethylene inserts retrieved postmortem from 20 subjects. The mean implantation time was 64.1 months (range, 4-156 months). The backsurface of the inserts was inspected using a stereomicroscope with a digital optical system. Coronal histologic sections of 13 proximal tibias were inspected for the presence and extent of penetration of granuloma. Damage to the backsurface was limited. Polishing was recorded on 21 (84%) of the inserts and abrasive wear on five (20%) inserts. Pitting was present in 21 (84%) components, but involved less than 1% of the area in all but one of these components. Delamination and cracking were not observed. Extrusions were seen in all 10 of the components that had screw holes in the tibial tray. A correlation was found between the depth of penetration of the granuloma along the posteromedial screw and the height of the corresponding extrusion. The anteroposterior profiles showed a concave deformation of the backsurface in 24 (96 %) of the cases. The concave deformation of tibial inserts may facilitate accumulation and transportation of wear debris to the tibial bone-implant interface through the screw holes in implants designed for cementless fixation.

Aged↗

Implant design affects markers of bone resorption and formation in total hip replacement.

Concentrations of the bone resorption markers pyridinoline and deoxypyridinoline and the bone formation marker osteocalcin were measured in 24-h urine collections from 30 subjects who underwent unilateral total hip replacements for monoarticular symptomatic osteoarthrosis and 10 controls. The patient groups were divided based on the femoral implant type (cemented cobalt alloy stem, cementless porous coated cobalt alloy stem, and cementless porous coated titanium alloy stem). Urine collections were performed before surgery and then at 3, 6, 12, 24, and 36 months. There were significant changes over time in the three patient groups for pyridinoline, deoxypyridinoline, and the ratio of osteocalcin to deoxypyridinoline (p < or = 0.01), but the control group values did not change over time. The resorption markers tended to peak at 3 months and the osteocalcin to deoxypyridinoline ratio was more variable, having depressed values in the cementless cobalt alloy group and elevated values in the other two groups compared with baseline. The cementless cobalt alloy group had higher resorption marker levels than the cemented cobalt alloy group at 6, 12, 24, and 36 months and higher levels than the cementless titanium alloy group at all postoperative times (p < 0.05). The osteocalcin to deoxypyridinoline ratio was lower in the cementless cobalt alloy group than in the cemented cobalt alloy group at 3, 6, and 24 months and the cementless titanium alloy group at 6, 12, and 24 months (p < 0.05). For the cemented cobalt chrome group, the baseline-normalized resorption marker values at 3 months and 6 months were correlated with the severity of radiographically assessed bone loss at 36 months (0.749 < r < 0.840; p < 0.05). For the cementless titanium alloy group, baseline-normalized osteocalcin/ deoxypyridinoline ratios at 3 months and 6 months were related inversely to radiographic bone loss at 36 months (0.687 < r < 0.749; p < 0.05). Thus, body fluid markers of bone metabolism change after total hip replacement. In addition, the changes in the marker concentrations were sensitive to implant design and were correlated with subsequent stress-shielding-induced bone loss.

Adult↗

Surface damage in machined ram-extruded and net-shape molded retrieved polyethylene tibial inserts of total knee replacements.

BACKGROUND: Polyethylene wear has emerged as a major determining factor in the long-term clinical performance of total knee replacements. This study addresses the in vivo wear performance of two types of polyethylene tibial inserts used in similar total knee arthroplasty designs. METHODS: A surface damage assessment of retrieved specimens was performed for twenty-six net-shape molded tibial inserts manufactured from H1900 resin without calcium stearate additive (Miller-Galante) and forty-three machined ram-extruded tibial inserts manufactured from GUR 4150 resin with calcium stearate additive (Miller-Galante II). Stereomicroscopic inspection and digital image analysis were used to quantify the extent and severity of pitting, dimensional change, and delamination. RESULTS: Pitting and dimensional change were the most common modes of damage in both groups, with the prevalence ranging from 77% to 92% for pitting and from 51% to 81% for dimensional change. Delamination was the least common mode of damage, with the prevalence ranging from 21% to 35%. The severity of pitting was higher in association with the cemented implant-bone interface. The extent and severity of delamination increased with implantation time. No severe delamination was observed before sixty months after implantation in the net-shape molded group, whereas severe delamination was present as early as ten months after implantation in the machined ram-extruded group. The time between surgery and the discovery of damage was longer in the net-shape molded group for all modes of damage except for medial dimensional change. CONCLUSIONS: On the basis of the components available in our implant retrieval pool, we found that at equivalent levels of surface damage, the net-shape molded H1900 resin tibial inserts demonstrated longer service life than did the machined ram-extruded GUR 4150 components. The superior performance of the net-shape molded components may be related to the resin type, the absence of calcium stearate, the consolidation method, or the method of final geometry shaping. This superior damage resistance is expected to contribute to superior long-term clinical performance of net-shape molded ultra-high molecular weight polyethylene in total knee arthroplasty.

Adult↗