Biomedical subjects

Victor M Goldberg

Publications and source records attributed to Victor M Goldberg.

At least 19 recordsLinked to original sources

PubMed2007

Evaluation of machining methods for trabecular metal implants in a rabbit intramedullary osseointegration model.

Implant success is dependent in part on the interaction of the implant with the surrounding tissues. Porous tantalum implants (Trabecular Metal, TM) have been shown to have excellent osseointegration. Machining this material to complex shapes with close tolerances is difficult because of its open structure and the ductile nature of metallic tantalum. Conventional machining results in occlusion of most of the surface porosity by the smearing of soft metal. This study compared TM samples finished by three processing techniques: conventional machining, electrical discharge machining, and nonmachined, "as-prepared." The TM samples were studied in a rabbit distal femoral intramedullary osseointegration model and in cell culture. We assessed the effects of these machining methods at 4, 8, and 12 weeks after implant placement. The finishing technique had a profound effect on the physical presentation of the implant interface: conventional machining reduced surface porosity to 30% compared to bulk porosities in the 70% range. Bone ongrowth was similar in all groups, while bone ingrowth was significantly greater in the nonmachined samples. The resulting mechanical properties of the bone implant-interface were similar in all three groups, with only interface stiffness and interface shear modulus being significantly higher in the machined samples.

Animals↗

PubMed2007

The balance between endotoxin accumulation and clearance during particle-induced osteolysis in murine calvaria.

Bacterial endotoxin may contribute to aseptic loosening of orthopedic implants even in the absence of clinical or microbiological evidence of infection. One potential source of endotoxin during aseptic loosening is systemically circulating endotoxin, derived from intestinal flora, minor infections, or dental procedures, that may bind to wear particles. The current study demonstrates that systemically derived endotoxin accumulates when 'endotoxin-free' titanium and polyethylene particles are implanted on murine calvaria. Time-course experiments and experiments using germ-free mice rule out the possibility that the observed endotoxin accumulation may be due to bacterial contamination. In contrast, endotoxin is cleared from titanium particles that originally carry high amounts of adherent endotoxin. The mechanism of endotoxin clearance is not dependent on induction of a respiratory burst. Taken together, these results indicate that a balance between endotoxin accumulation and endotoxin clearance controls the steady-state level of endotoxin surrounding orthopedic wear particles implanted on murine calvaria. This balance may regulate the rate of osteolysis in the murine calvaria model as well as in patients with aseptic loosening.

Animals↗

PubMed2006

A rapid seeding technique for the assembly of large cell/scaffold composite constructs.

These studies address critical technical issues involved in creating human mesenchymal stem cell (hMSC)/ scaffold implants for cartilage repair. These issues include obtaining a high cell density and uniform spatial cell distribution within the scaffold, factors that are critical in the initiation and homogeneity of chondrogenic differentiation. For any given scaffold, the initial seeding influences cell density, retention, and spatial distribution within the scaffold, which eventually will affect the function of the construct. Here, we discuss the development of a vacuum-aided seeding technique for HYAFF -11 sponges which we compared to passive infiltration. Our results show that, under the conditions tested, hMSCs were quantitatively and homogeneously loaded into the scaffolds with 90+% retention rates after 24 h in perfusion culture with no negative effect on cell viability or chondrogenic potential. The retention rates of the vacuum-seeded constructs were at least 2 times greater than those of passively seeded constructs at 72 h. Histomorphometric analysis revealed that the core of the vacuum-seeded constructs contained 240% more cells than the core of passively infiltrated scaffolds. The vacuum seeding technique is safe, rapid, reproducible, and results in controlled quantitative cell loading, high retention, and uniform distribution.

Biocompatible Materials↗

PubMed2006

Lipopolysaccharide found in aseptic loosening of patients with inflammatory arthritis.

Aseptic loosening of orthopaedic implants occurs in the absence of clinical signs of infection. Nevertheless, bacterial endotoxins derived from subclinical infections, systemic sources, or the implant manufacturing process may contribute to aseptic loosening. Also, the rate of implant infection is greater in patients with inflammatory arthritis than in patients with osteoarthritis. We hypothesized that lipopolysaccharide, the classic endotoxin derived from gram-negative bacteria, is more prevalent in periprosthetic tissue surrounding aseptically loose implants in patients with inflammatory arthritis than in patients with osteoarthritis. To test this, we used a modified Limulus amebocyte assay not affected by beta-glucan-like molecules in mammalian tissues. Lipopolysaccharide rarely was detected in periprosthetic tissue from patients with osteoarthritis and aseptic loosening (one of six patients). In contrast, lipopolysaccharide was detected despite the absence of any clinical signs of infection in peri-prosthetic tissue from all four patients with inflammatory arthritis (rheumatoid arthritis, juvenile rheumatoid arthritis, and systemic lupus erythematosus). Lipopolysaccharide also was detected in two patients with gram-negative infections, who were included as positive control subjects. Endotoxins derived from low-grade or systemic bacteremia may be important contributors to aseptic loosening particularly in patients with autoimmune conditions such as inflammatory arthritis.

Adult↗

PubMed2006

Toxic effects of gentamicin on marrow-derived human mesenchymal stem cells.

We hypothesized that the high concentrations of gentamicin achieved after local administration would have toxic effects on human mesenchymal stem cells. These cells were isolated from bone marrow from three healthy adult donors and cultured with different concentrations of gentamicin (0 microg/mL, 50 microg/mL, 100 microg/mL, and 200 microg/mL) for 7 days. After 7 days of gentamicin exposure, we examined cell viability, proliferation, and in vitro and in vivo osteochondrogenic capacity. Gentamicin did not have an adverse effect on the viability of human mesenchymal stem cells in all test groups, but did inhibit cell proliferation at concentrations of 100 microg/mL and 200 microg/mL. In in vitro osteogenesis, gentamicin decreased the DNA content and alkaline phosphatase activity of human mesenchymal stem cells at an early stage (Days 4 and 8) in a dose-dependent manner. For chondrogenesis, glycosaminoglycan content and Type II and Type X collagen deposition were lower in the pellets made with cells expanded in gentamicin at 100 or 200 microg/mL relative to cells expanded in medium without gentamicin. A comparable effect on osteochondrogenesis was observed in an in vivo model. At a high concentration, gentamicin inhibits proliferation and differentiation of human bone marrow mesenchymal stem cells and could compromise the bone-healing process.

Anti-Bacterial Agents↗

PubMed2006

2006 Otto Aufranc Award Paper: significance of in vivo degradation for polyethylene in total hip arthroplasty.

Our research group developed an implant retrieval program to study in vivo degradation of polyethylene. We now have evidence to support our hypothesis that degradation of radiation-sterilized polyethylene occurs in the body for not only historical gamma air sterilized liners, but also for conventional gamma inert sterilized (ArCom) and annealed highly crosslinked polyethylene (Crossfire) liners as well. Our research has also led to the discovery that the most severe manifestations of in vivo oxidation typically occur in regions of the liner experiencing minimal wear, such as the rim of the component, where the body fluids (containing oxidizing species) have access to the polyethylene. Our data from historical, ArCom, and Crossfire retrievals all point to a similar scenario in which the femoral head limits the in vivo oxidation of polyethylene at the bearing surface. Consequently, provided rim impingement does not occur, and the polyethylene locking mechanisms remain relatively isolated from oxidizing fluid, in vivo oxidation does not seem to be clinically important in the first 10 years of implantation for conventional gamma sterilized polyethylene. We conclude that in vivo degradation should be included among the list of potential long-term failure modes for modular polyethylene components for total hip arthroplasty.

Arthroplasty, Replacement, Hip↗

PubMed2006

Clinical and histologic results related to a low-modulus composite total hip replacement stem.

BACKGROUND: Osteolysis secondary to stress shielding in patients with a total hip arthroplasty has been attributed to greater stiffness of the prosthetic femoral stem compared with the stiffness of the femur. This concern led to the development of a composite femoral stem implant with a structural stiffness similar to that of the native femur. The stem consists of a cobalt-chromium-alloy core surrounded by polyaryletherketone and titanium mesh for bone ingrowth. The purpose of this study was to determine the intermediate-term clinical, radiographic, and histologic results of the use of this stem. METHODS: Twenty-eight patients (nineteen men and nine women) with an average age of 51.3 years underwent primary total hip arthroplasty with the Epoch stem and were followed for an average of 6.2 years. Harris hip scores were determined and radiographic studies were performed preoperatively, postoperatively, and at two-year intervals thereafter. In addition, dual x-ray absorptiometry scans were made up to two years postoperatively to evaluate osseous resorption. Two femora obtained at autopsy thirteen and forty-eight months after surgery were analyzed for bone ingrowth and ongrowth. RESULTS: The Harris hip scores averaged 56 points preoperatively and improved to 97 points at the time of the last follow-up. Dual x-ray absorptiometry scans demonstrated the greatest decrease in mean bone density (27.5%) in Gruen zone 7 at two years. Radiographs demonstrated no instances of migration, and only one hip had osteolysis. All stems had stable osseous fixation. Histologic evaluation of the two femora that had been retrieved at autopsy at thirteen and forty-eight months showed the mean bone ingrowth (and standard deviation) along the entire length of the stem to be 49.62% +/- 13.04% and 73.57% +/- 8.48%, respectively, and the mean bone ongrowth to be 54.18% +/- 7.68% and 80.92% +/- 6.06%, respectively. CONCLUSIONS: Intermediate-term follow-up of hips treated with the Epoch stem indicated excellent clinical success, radiographic evidence of osseous integration, and histologic findings of osseous ingrowth and ongrowth. Although the implant has been associated with excellent results in both the short and the intermediate term, longer follow-up will be necessary to assess the long-term function of the implant.

Adult↗

PubMed2005

Does endotoxin contribute to aseptic loosening of orthopedic implants?

Aseptic loosening of orthopedic implants caused by wear particles is a major clinical problem. This review examines the hypothesis that bacterial endotoxin contributes to aseptic loosening. Clinical findings support this hypothesis: bacterial biofilms exist on many implants from patients with aseptic loosening and antibiotics in bone cement reduce the rate of aseptic loosening. Three approaches were used to demonstrate that adherent endotoxin increases bioactivity of titanium particles. These experiments measured cytokine production and osteoclast differentiation in vitro and murine calvarial osteolysis in vivo. First, removal of >99.9% of the adherent endotoxin from titanium particles significantly ablates their biological activity. Second, adding lipopolysaccharide back to these "endotoxin-free" particles restores their biological activity. Third, cells or mice that are genetically hyporesponsive to endotoxin are significantly less responsive to titanium particles than are wild-type controls. Other investigators have confirmed and extended these results to include virtually all orthopedically relevant types of particles, including authentic titanium alloy particles retrieved from patients with loosening. Our recent studies suggest that adherent endotoxin on orthopedic implants may also inhibit initial osseointegration of the implants. Taken together, these studies suggest that bacterial endotoxin may have a significant role in induction of aseptic loosening.

Animals↗

PubMed2005

Sustained Wnt protein expression in chondral constructs from mesenchymal stem cells.

Wnt genes encode a number of secreted glycoproteins which are closely associated with the cell surface and the extracellular matrix. Recently, members of Wnt family have been implicated in regulating chondrocyte differentiation, but their roles in the chondrogenic process are not fully understood. To contribute to an understanding of the roles of Wnts during chondrogenesis, we have analysed the spatiotemporal expression patterns of Wnt using in vitro models for chondrogenesis of human bone marrow-derived mesenchymal stem cells (hMSCs). In chondrogenic aggregate culture system, RT-PCR analysis revealed expression of Wnt5a and Wnt4 during late chondrogenesis (days 10 and 15). Immunohistochemical analysis showed widespread distribution of Wnt5a and Wnt4 throughout the aggregates at this late phase of culture (days 14 and 21). In addition, in this aggregate culture system, immunohistochemical staining of Wnt4 and Wnt5a showed similar spatiotemporal expression patterns to that of type II collagen or type X collagen. To confirm the results obtained by immunostaining, the specificity of the anti-Wnt4 or anti-Wnt5a antibody was assessed by Western blot analysis. Of Wnt4 and Wnt5a, only Wnt5a was immunodetectable by Western blot analysis. Western blot analysis showed that Wnt5a was expressed as two different molecular weight forms of 40 and 44 kDa. Treatment with PNGase F, which removes N-linked oligosaccharides, revealed that the mass difference between these two forms could be accounted for by the N-glycosylation status of the protein. When hMSCs were seeded on a porous gelatin sponge, immunolocalization studies showed that type II collagen and type X collagen were detected particularly at the periphery at day 7 of culture. In contrast, Wnt4 and Wnt5a showed even distribution throughout the hMSC/gelatin sponge constructs. Their different spatial expression patterns suggest that Wnt4 and Wnt5a proteins are not functionally linked to type II collagen and type X collagen synthesis in in vitro chondrogenic models of hMSCs.

Blotting, Western↗

PubMed2005

FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) expanded with and without fibroblast growth factor (FGF) supplementation were compared with respect to their proliferation rate, ability to differentiate along the chondrogenic pathway in vitro, and their gene expression profiles. hMSCs expanded in FGF-supplemented medium were smaller and proliferated more rapidly than hMSCs expanded in control conditions. Chondrogenic cultures made with FGF-treated cells were larger and contain more proteoglycan than those made with control cells. Furthermore, aggregates of FGF-treated cells lacked the collagen type I-positive and collagen type II-negative outer layer characteristic of aggregates of control cells. A total of 358 unique transcripts were differentially expressed in FGF-treated hMSCs. Of these, 150 were upregulated and 208 downregulated. Seventeen percent of these genes affect proliferation. Known genes associated with cellular signaling functions comprised the largest percentage ( approximately 20%) of differentially expressed transcripts. Eighty percent of differentially expressed extracellular matrix-related genes were downregulated. The present findings that FGF-2 enhances proliferation and differentiation of hMSCs adds to a growing body of evidence that cytokines modulate the differentiation potential and, perhaps, the multipotentiality of adult stem cells. With the generation of gene expression profiles of FGF-treated and control cells we have taken the first steps in the elucidation of the molecular mechanism(s) behind these phenomena.

Age Factors↗

PubMed2005

Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds.

OBJECTIVE: The natural repair of osteochondral defects can be enhanced with biocompatible, biodegradable materials that support the repair process. It is our hypothesis that hyaluronan-based scaffolds are superior to synthetic scaffolds because they provide biological cues. We tested this thesis by comparing two hyaluronan-based scaffolds [auto cross-linked polysaccharide polymer (ACP) and HYAFF-11] to polyester-based scaffolds [poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA)] with similar pore size, porosity and degradation times. DESIGN: Fifty-four rabbits received bilateral osteochondral defects. One defect received a hyaluronan-based scaffold and the contralateral defect received the corresponding polyester-based scaffold. Rabbits were euthanized 4, 12 and 20 weeks after surgery and the condyles dissected and processed for histology. RESULTS: Only ACP-treated defects presented bone at the base of the defect at 4 weeks. At 12 weeks, only defects treated with rapidly dissolving implants (ACP and PLGA) presented bone reconstitution consistently, while bone was present in only one third of those treated with slowly dissolving scaffolds (HYAFF-11 and PLLA). After 20 weeks, the articular surface of PLGA-treated defects presented fibrillation more frequently than in ACP-treated defects. The surface of defects treated with slowly dissolving scaffolds presented more cracks and fissures. CONCLUSIONS: The degradation rate of the scaffolds is critical for the repair process. Slowly dissolving scaffolds sustain thicker cartilage at the surface but, it frequently presents cracks and discontinuities. These scaffolds also delay bone formation at the base of the defects. Hyaluronan-based scaffolds appear to allow faster cell infiltration leading to faster tissue formation. The degradation of ACP leads to rapid bone formation while the slow degradation of HYAFF-11 prolongs the presence of cartilage and delays endochondral bone formation.

Animals↗

PubMed2005

Polyethylene and titanium particles induce osteolysis by similar, lymphocyte-independent, mechanisms.

Periprosthetic osteolysis is a major clinical problem that limits the long-term survival of total joint arthroplasties. Osteolysis is induced by implant-derived wear particles, primarily from the polyethylene bearing surfaces. This study examined two hypotheses. First, that similar mechanisms are responsible for osteolysis induced by polyethylene and titanium particles. Second, that lymphocytes do not play a major role in particle-induced osteolysis. To test these hypotheses, we used the murine calvarial model that we have previously used to examine titanium-induced osteolysis. Polyethylene particles rapidly induced osteolysis in the murine calvaria 5-7 days after implantation. The polyethylene-induced osteolysis was associated with large numbers of osteoclasts as well as the formation of a thick periosteal fibrous tissue layer with numerous macrophages containing phagocytosed polyethylene particles. Polyethylene-induced osteolysis was rapidly repaired and was undetectable by day 21 after implantation. Lymphocytes were noted in the fibrous layer of wild-type mice. However, the amount of osteolysis and cytokine production induced by polyethylene particles was not substantially affected by the lack of lymphocytes in Pfp/Rag2 double knock out mice. All of these findings are similar to our observations of osteolysis induced by titanium particles. These results provide strong support for both of our hypotheses: that similar mechanisms are responsible for osteolysis induced by polyethylene and titanium particles and that lymphocytes do not play a major role in particle-induced osteolysis.

Animals↗

PubMed2005

Revision of the patella with deficient bone using a biconvex component.

UNLABELLED: Revision surgery on a failed patellar component can be difficult because of deficient residual bone that may compromise the functional outcome of the revision. We reviewed 20 knees in 20 patients in whom the residual patellar bone was less than 10 mm at the time of revision and used the Genesis Biconvex Patella implant to reconstruct the patella. The patients were followed up for an average of 34 months (range, 24-65 months), and were followed up clinically and radiographically by Knee Society criteria. Patellar revisions and complications were noted and standard radiographic studies to ascertain radiolucent lines and patella/patellar component thickness were evaluated. The Knee Society Scores improved from an average of 45 points to 89 points. Function scores improved from an average of 47 points to 65 points. None of the patients has required revision surgery and no patellar fractures have been seen. Radiographs showed complete lucencies at the cement-bone interface in two knees. The mean residual central patella bone thickness was 6.5 mm and the average postoperative composite thickness was 14.5 mm. The data indicate that the use of the Genesis Biconvex Patella implant is a satisfactory method of treating revision of the patella when there is major bone deficiency. LEVEL OF EVIDENCE: Retrospective study, Level IV-1 (case study). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗

PubMed2005

Cementless two-staged total hip arthroplasty for deep periprosthetic infection.

UNLABELLED: bTwo-staged exchange with delayed reimplantation of a new prosthesis is considered by many to be the preferred method of treatment for deep periprosthetic infection after total hip arthroplasty. Until recently, most authors of previously published reports of this two-staged exchange procedure have used cemented implants fixed with antibiotic-containing bone cement. In view of the superior results of revision total hip arthroplasties with cementless implants, we reviewed the results of 33 two-staged revision total hip arthroplasties done for deep infection using cementless femoral components. There were no recurrent infections in the 28 patients in this study who had a 2-year minimum followup. Two patients developed a new infection with a different organism after reimplantation of their hip. Three patients with considerable acetabular bone deficiency had acetabular component revision for aseptic loosening; however, there were no cases of femoral component loosening. The overall infection rate of 7% using this approach was comparable to previous reports of two-staged revision total hip arthroplasties done with cemented components fixed with antibiotic-containing bone cement. In addition, cementless femoral component fixation seemed to be more reliable and durable in comparison to previous reports of revision total hip arthroplasty with cemented stems. The results of this study support the continued use of cementless implant fixation for two-staged reconstruction of the infected total hip arthroplasty. LEVEL OF EVIDENCE: Therapeutic study, Level IV-1 (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗

PubMed2005

In vivo degradation of polyethylene liners after gamma sterilization in air.

BACKGROUND: Ultra-high molecular weight polyethylene degrades during storage in air following gamma sterilization, but the extent of in vivo degradation remains unclear. The purpose of this study was to quantify the extent to which the mechanical properties and oxidation of conventional polyethylene acetabular liners treated with gamma sterilization in air change in vivo. METHODS: Fourteen modular cementless acetabular liners were revised at an average of 10.3 years (range, 5.9 to 13.5 years) after implantation. All liners, which had been machined from GUR 415 resin, had been gamma-sterilized in air; the average shelf life was 0.3 year (range, 0.0 to 0.8 year). After removal, the components were expeditiously frozen to minimize ex vivo changes to the polyethylene prior to characterization. The average duration between freezing and testing was 0.6 year. Mechanical properties and oxidation were measured with use of the small-punch test and Fourier transform infrared spectroscopy, respectively, in the loaded and unloaded regions of the liners. RESULTS: There was substantial regional variation in the mechanical properties and oxidation of the retrieved liners. The ultimate load was observed to vary by >90% near the surface. On the average, the rim and the unloaded bearing showed evidence of severe oxidation near the surface after long-term in vivo aging, but these trends were not typically observed on the loaded bearing surface or near the backside of the liners. CONCLUSIONS: The mechanical properties of polyethylene that has been gamma-sterilized in air may decrease substantially in vivo, depending on the location in the liner. The most severe oxidation was observed at the rim, suggesting that the femoral head inhibits access of oxygen-containing body fluids to the bearing surface. This is perhaps why in vivo oxidation has not been associated with clinical performance to date.

Acetabulum↗

PubMed2005

Surface replacement solutions for the arthritic hip.

Surface replacement is a conservative treatment for young, active patients with hip osteoarthritis. It provides an increased range of motion as the result of a larger diameter head and improved wear characteristics because of the metal-on-metal articulation as well as an extremely low dislocation rate and increased patient function. While early results are encouraging, long-term outcomes are necessary to define and delineate the role of surface replacement arthroplasty in the treatment of significant hip arthritis.

Arthroplasty, Replacement, Hip↗

PubMed2004

Effect of hydroxyapatite/tricalcium-phosphate coating on osseointegration of plasma-sprayed titanium alloy implants.

This study determined the effects of a plasma-sprayed hydroxyapatite/tricalcium phosphate (HA/TCP) coating on osseointegration of plasma-sprayed titanium alloy implants in a lapine, distal femoral intramedullary model. The effects of the HA/TCP coating were assessed at 1, 3, and 6 months after implant placement. The HA/TCP coating significantly increased new bone apposition onto the implant surfaces at all time points. The ceramic coating also stimulated intramedullary bone formation at the middle and distal levels of the implants. Fluorescent bone labeling indicated that new bone formation occurred primarily during the first 3 months after implantation, with comparatively little activity detected in the latter stages of the study. There was no associated increase in pullout strength at either 3 or 6 months; however, post-pullout evaluation of the implants indicated that the HA/TCP coating itself was not the primary site of construct failure. Rather, failure was most commonly observed through the periprosthetic osseous struts that bridged the medullary cavity. The demonstrated osteoconductive activity of HA/TCP coating on plasma-sprayed titanium alloy implant surfaces may have considerable clinical relevance to early host-implant interactions, by accelerating the establishment of a stable prosthesis-bone interface.

Alloys↗

PubMed2004

Effects of calcium ion implantation on osseointegration of surface-blasted titanium alloy femoral implants in a canine total hip arthroplasty model.

Osteoconductivity of titanium-alloy implants may be improved when surface-modified by calcium ion (Ca2+) implantation. We studied the effects of Ca2+ implantation on osseointegration of a grit-blasted titanium-alloy stem using a canine total hip arthroplasty model. Fifteen dogs underwent bilateral hip arthroplasties and were sacrificed at 1, 6, and 12 months postoperatively. The hip components were evaluated by radiographic, qualitative, and quantitative histology methods. Radiographically and histologically, both Ca(2+)-implanted and non-Ca(2+)-implanted stems were well integrated. Ca(2+)-implanted stems had greater new bone apposition than non-Ca(2+)-implanted stems, although the difference was significant only at 1 month (15.8% +/- 3.5% of the implant perimeter for non-Ca(2+)-implanted, 25.4% +/- 4.7% for Ca(2+)-implanted, P< .05). This result could be related to chronological decrease of the dissolution rate of calcium ions from Ca(2+)-implanted surface. Although further improvement of the Ca2+ implantation technique for a sustained osteoconductive effect is necessary, Ca2+ implantation may be beneficial for early fixation of titanium-alloy implants.

Alloys↗