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Biomedical subjects

Joshua J Jacobs

Publications and source records attributed to Joshua J Jacobs.

At least 19 recordsLinked to original sources
PubMed2006

Stem diameter and rotational stability in revision total hip arthroplasty: a biomechanical analysis.

BACKGROUND: Proximal femoral bone loss during revision hip arthroplasty often requires bypassing the deficient metaphyseal bone to obtain distal fixation. The purpose of this study was to determine the effect of stem diameter and length of diaphyseal contact in achieving rotational stability in revision total hip arthroplasty. METHODS: Twenty-four cadaveric femoral specimens were implanted with a fully porous-coated stem. Two different diameters were tested and the stems were implanted at multiple contact lengths without proximal bone support. Each specimen underwent torsional testing to failure and rotational micromotion was measured at the implant-bone interface. RESULTS: The larger stem diameter demonstrated a greater torsional stability for a given length of cortical contact (p <or= 0.05). Decreasing length of diaphyseal contact length was associated with less torsional stability. Torsional resistance was inconsistent at 2 cm of depth. CONCLUSION: Larger stem diameters frequently used in revisions may be associated with less diaphyseal contact length to achieve equivalent rotational stability compared to smaller diameter stems. Furthermore, a minimum of 3 cm or 4 cm of diaphyseal contact with a porous-coated stem should be achieved in proximal femoral bone deficiency and will likely be dependent on the stem diameter utilized at the time of surgery.

Journal Article↗
PubMed2006

Experimental and clinical performance of porous tantalum in orthopedic surgery.

Porous tantalum, a new low modulus metal with a characteristic appearance similar to cancellous bone, is currently available for use in several orthopedic applications (hip and knee arthroplasty, spine surgery, and bone graft substitute). The open-cell structure of repeating dodecahedrons is produced via carbon vapor deposition/infiltration of commercially pure tantalum onto a vitreous carbon scaffolding. This transition metal maintains several interesting biomaterial properties, including: a high volumetric porosity (70-80%), low modulus of elasticity (3MPa), and high frictional characteristics. Tantalum has excellent biocompatibility and is safe to use in vivo as evidenced by its historical and current use in pacemaker electrodes, cranioplasty plates and as radiopaque markers. The bioactivity and biocompatibility of porous tantalum stems from its ability to form a self-passivating surface oxide layer. This surface layer leads to the formation of a bone-like apatite coating in vivo and affords excellent bone and fibrous in-growth properties allowing for rapid and substantial bone and soft tissue attachment. Tantalum-chondrocyte composites have yielded successful early results in vitro and may afford an option for joint resurfacing in the future. The development of porous tantalum is in its early stages of evolution and the following represents a review of its biomaterial properties and applications in orthopedic surgery.

Animals↗
PubMed2006

The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis.

OBJECTIVE: This study was undertaken to investigate how fibroblasts respond to stimulation with particulate wear debris and/or conditioned media obtained from pathologic tissue, and whether these activated fibroblasts express compounds that are involved in bone resorption. METHODS: Conditioned media from explant cultures of synovial tissue, periprosthetic soft tissue (interface membranes), titanium particles, and proinflammatory cytokines were used to stimulate fibroblasts. RNase protection assay was used to measure altered gene expression, and enzyme-linked immunosorbent assay, Western blot hybridization, and flow cytometry were used to determine fibroblast protein expression. Tartrate-resistant acid phosphatase staining was used to identify multinucleated osteoclast-like cells. RESULTS: The most dominant compounds measured in the conditioned media from interface membranes were tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein 1 (MCP-1), interleukin-1beta (IL-1beta), IL-6, IL-8, and vascular endothelial growth factor. Fibroblasts phagocytosed particulate wear debris and responded to cytokine/chemokine stimulation. The most prominent up-regulated genes and proteins secreted by fibroblasts in response to stimulation were matrix metalloproteinase 1, MCP-1, IL-1beta, IL-6, IL-8, cyclooxygenase 1 (COX-1), COX-2, leukemia inhibitory factor 1, transforming growth factor beta1 (TGFbeta1), and TGFbeta receptor type I. In addition, interface membrane fibroblasts expressed RANKL and osteoprotegerin in response to stimulation with conditioned media, TNFalpha, or IL-1beta. Stimulated fibroblasts cocultured with bone marrow cells in the presence of macrophage colony-stimulating factor induced osteoclastogenesis. CONCLUSION: Interface membrane fibroblasts respond directly to particulate wear debris, possibly via phagocytosis, expressing proinflammatory cytokines and RANKL. Thus, these cells may be actively involved in osteoclastogenesis and pathologic (periprosthetic) bone resorption.

Adult↗
PubMed2006

Chemokine gene activation in human bone marrow-derived osteoblasts following exposure to particulate wear debris.

Particulate wear debris induces the expression of pro-inflammatory cytokine and chemokine genes in various cell types of the periprosthetic region. We have previously reported that titanium particles stimulate the selective induction of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) chemokines in human osteoblast-like osteosarcoma cells. In this study, we characterize the human bone marrow-derived osteoblast chemokine response to titanium particles. We demonstrate that titanium particles result in enhanced IL-8 and MCP-1 protein secretion as well as differential chemokine gene activation. Osteoblast chemokine expression was regulated at the level of gene transcription, with a time-dependent induction of NF-kappaB activation. Inhibition studies with N-acetyl-L-cysteine (Nac) and MG-132 suggest that titanium particle activation of NF-kappaB activity and IL-8 chemokine expression involves oxidant signaling and IkappaBalpha-proteasomal degradation. Activation of the NF-kappaB transcription factor, as well as the IL-8 gene, are redox-regulated. We also demonstrate that while cytochalasin D, a potent inhibitor of phagocytosis, suppressed the titanium particle effect on IL-8 protein release in human bone marrow-derived osteoblasts, the inhibitor had no effect on IL-8 expression in MG-63 osteoblast-like cells. Collectively, these results provide insight into the potential mechanisms responsible for the particulate activation of osteoblast chemokine expression and suggest an important role for the osteoblast in the pathogenesis of periprosthetic osteolysis.

Adult↗
PubMed2006

Clinical performance of contemporary tibial polyethylene components.

A postclinical retrieval analysis was performed on 43 polyethylene tibial components of a contemporary total knee arthroplasty system with implantation duration between 12 and 80 months. Components were scored for 8 potential modes of surface wear or damage on the top and back surfaces. Moderate backside wear of 4.1 microm/y was documented by measuring the extent of manufacturer's engraved lettering removal. Neither the topside nor backside score correlated with duration of in vivo function. No component experienced topside or backside delamination, cracking, or significant deformation. The greatest contribution to wear and damage score was pitting and scratching secondary to bone cement debris. The extent of both wear and damage experienced by these components was moderate, in comparison with that previously reported with older implant systems.

Arthroplasty, Replacement, Knee↗
PubMed2006

Serum metal levels and bearing surfaces in total hip arthroplasty.

This study evaluates steady-state serum metal levels in patients with 4 different combinations of fixation modalities, materials, and bearing couples. Forty patients with a minimum of 5 years of follow-up and with well-functioning primary total hip arthroplasty were recruited to have serum metal levels measured. Serum chromium and cobalt levels in the metal-on-metal cohort were significantly higher (P < .05) than the other 3 cohorts. The noncemented ceramic-polyethylene cohort had significantly lower (P < .05) serum chromium levels compared to cemented and noncemented metal-polyethylene cohorts and significantly higher serum titanium levels compared to the cemented metal-polyethylene cohort which had no titanium-containing implants. Debris generated at the metal head/neck modular junction likely accounts for the significantly lower serum chromium concentration in ceramic-polyethylene bearing couples.

Aged↗
PubMed2006

Wear particles.

Particulate and ionic debris resulting from in vivo degradation of total joint replacement components are recognized as major factors limiting the longevity of the joint reconstruction and the overall success of the procedure. Particulate and ionic wear and corrosion debris have been associated with a locally aggressive biologic response that can lead to synovitis, periprosthetic bone loss, and aseptic loosening of the implants. Furthermore, concerns exist regarding the systemic dissemination of prosthetic debris, including potential effects resulting from end-organ retention. The long-term success of total disc arthroplasty may well depend, at least in part, on the ability to minimize implant debris generation and the subsequent local and systemic response.

Arthroplasty, Replacement↗
PubMed2006

Applications of porous tantalum in total hip arthroplasty.

Porous tantalum is an alternative metal for total joint arthroplasty components that offers several unique properties. Its high volumetric porosity (70% to 80%), low modulus of elasticity (3 MPa), and high frictional characteristics make it conducive to biologic fixation. Tantalum has excellent biocompatibility and is safe to use in vivo. The low modulus of elasticity allows for more physiologic load transfer and relative preservation of bone stock. Because of its bioactive nature and ingrowth properties, tantalum is used in primary as well as revision total hip arthroplasty components, with good to excellent early clinical results. In revision arthroplasty, standard and custom augments may serve as a structural bone graft substitute. Formation of a bone-like apatite coating in vivo affords strong fibrous ingrowth properties and allows for substantial soft-tissue attachment, indicating potential for use in cases requiring reattachment of muscles and tendons to a prosthesis. Development of modular components and femoral stems also is being evaluated. The initial clinical data and basic science studies support further investigation of porous tantalum as an alternative to traditional implant materials.

Animals↗
PubMed2005

Effects of soluble metals on human peri-implant cells.

Despite reports associating tissue necrosis with implant failure, the degree to which processes, such as metal toxicity, negatively impact implant performance is unknown. We evaluated representative human peri-implant cells (i.e., osteoblasts, fibroblasts, and lymphocytes) when challenged by Al+3, Co+2, Cr+3, Fe+3, Mo+5, Ni+2, and V+3 chloride solutions (and Na+2 as a control) over a wide range of concentrations (0.01-10.0 mM). Cell responses were measured using proliferation assays, viability assays, and microscopic cell morphology assessments. Differential effects were found to be less a function of the cell type than of the composition and concentration of metal challenge. No preferential immunosuppression was demonstrated. Below 0.01 mM, no metal was toxic. The most toxic metals (i.e., Co, Ni, and V) reduced proliferation (IC50), and viability (LC50) and cell morphology of osteoblasts, fibroblasts, and lymphocytes by <50% at challenge concentrations <1 mM. All other metals tested required >5 mM to exact the same responses. Below 1 mM, these toxic metals also induced alterations in all cell morphology consisting of loss of filopodia or lamellipodia or changes in cell shape. Metals that were toxic at clinically relevant concentrations (less than previously reported values in peri-implant tissues/fluids) include Co (0.6 mM), Ni (0.8 mM), V (0.5 mM) for lymphocytes and Co (0.8 mM), V (0.3 mM), Al (1-5 mM), Fe (1-5 mM) for fibroblasts, and Co (0.8 mM), Ni (0.7 mM), V (0.1 mM) for osteoblasts. Only Co and V were toxic in vitro at concentrations below that detected in vivo in synovial fluid (V at 0.1 mM and Co at 0.8 mM for fibroblasts, and V at 0.4 mM and Co at 0.8 mM on osteoblasts). Thus, soluble Co and V released from Co- and Ti-based alloys, respectively, could be implicated as the most likely to mediate cell toxicity in the periprosthetic milieu.

Animals↗
PubMed2005

Chemokine IL-8 induction by particulate wear debris in osteoblasts is mediated by NF-kappaB.

Chemokines, or chemotactic cytokines, are major regulators of the inflammatory response and have been identified as pathogenic factors in the periprosthetic soft tissue. Particulate wear debris induced NF-kappaB activation, the major transcriptional regulator of IL-8 and MCP-1 pro-inflammatory genes and, indeed, both IL-8 and MCP-1 chemokine gene expressions were upregulated in titanium particulate-stimulated human osteoblasts. Here, we demonstrate that phagocytosed particles activate the IL-8 gene promoter via a NF-kappaB-mediated mechanism. Transfection of a dominant negative mutant IkappaBalpha protein that cannot be serine phosphorylated led to suppression of IL-8 promoter activity. The p65/RelA NF-kappaB subunit activity was affected in both a time- and titanium particle concentration-dependent fashion. Titanium particles led to increased ERK, JNK, and p38 activation in MG-63 osteoblast cells, and IL-8 protein release was suppressed by specific inhibitors of the ERK and p38 MAPK pathways. Together, our results suggest that wear debris particles induce chemokine expression in osteoblasts via NF-kappaB-mediated transcriptional activation, which is controlled by the MAPK signal transduction pathway.

Cell Line, Tumor↗
PubMed2005

The acetabular insert-metal backing interface: an additional source of polyethylene wear debris.

In cementless acetabular arthroplasty, the interface between the metal backing and the ultra-high-molecular-weight polyethylene acetabular insert surface is a potential source of polyethylene debris. This study of 55 early-generation acetabular inserts found that severe wear of the convex insert surface correlates with osteolysis. Wear of the concave insert surface did not correlate strongly with osteolysis probably owing to prevalent micromotion and wear at the convex surface interface. Although concern over linear wear predominates with contemporary designs, if initial liner engagement is compromised or locking mechanism failure occurs with time, the convex insert surface again may become a significant source of debris contributing to osteolysis.

Acetabulum↗