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Biomedical subjects

N Rushton

Publications and source records attributed to N Rushton.

At least 19 recordsLinked to original sources
PubMed2006

Human osteoblast response to silicon-substituted hydroxyapatite.

Human osteoblasts were cultured on hydroxyapatite (HA), 0.8 wt % silicon substituted hydroxyapatite (Si-HA) and 1.5 wt % Si-HA discs. The influence of these substrates on cell behaviour in vitro was assessed by measuring total protein in the cell lysate and the production of several phenotypic markers: collagen type I (COL I), alkaline phosphatase (ALP), osteocalcin (OC), and the formation of bone mineral. After 7 days, beta-glycerophosphate and physiological levels of hydrocortisone were added to the culture medium to stimulate cell differentiation and mineral production. There was a significantly higher production of ALP on 1.5 wt % Si-HA at day 7 following which, the addition of hydrocortisone promoted the differentiation of cells on the other two substrates. Hydrocortisone addition also decreased the production of OC. During the period, when hydrocortisone was present, no significant difference in behavior was seen between cells on Si-HA and HA; however, following removal of hydrocortisone, cells responded to 0.8 wt % Si-HA with a significant increase in protein production. Using fluorescence microscopy, nodular structures labeled with tetracycline were observed on the surface of all substrates after 21 days. These structures were deposited on areas of high cell density but were not related to the presence or level of silicon in the substrate. These results indicate that human osteoblasts are affected by the presence of silicon in the HA substrate and that the timing of these effects may be dependent upon the level of silicon substitution.

Cells, Cultured↗
PubMed2006

Differentiation of mononuclear precursors into osteoclasts on the surface of Si-substituted hydroxyapatite.

In healthy bone, resorption and synthesis are in perfect coordination. In previous studies we demonstrated that the incorporation of silicon into the hydroxyapatite (HA) lattice enhances the proliferation and differentiation of human osteoblasts. Therefore, the aim of this study was to demonstrate the effect of silicon-substituted HA (0.8 and 1.5 wt % Si-HA) on the differentiation of mononuclear cells into osteoclasts, using two different starting cultures, peripheral blood mononuclear cells (PBMC) and monocytes expressing the CD14 antigen (CD14+). Through this study, it was possible to demonstrate that Si-HA allows the differentiation of mononuclear cells into mature osteoclasts, independent of the starting culture, PBMC or CD14+. Most of the cells on the surface of the materials expressed osteoclastic markers: actin rings, several nuclei, positivity for tartrate-resistant acid phosphatase (TRAP), and vitronectin receptor. In the presence of osteoclasts, a higher release of calcium and phosphate into the medium from the 1.5 wt % Si-HA substrate was detected when compared to the HA substrate; therefore, these results indicate higher osteoclastic resorptive activity on the 1.5 wt % Si-HA surface. Si-HA can be resorbed by cellular mechanisms and have a stimulatory effect on osteoclasts, although the underlying mechanism is still poorly understood.

Cell Differentiation↗
PubMed2006

Biomechanics of the Birmingham hip resurfacing arthroplasty.

The effects of the method of fixation and interface conditions on the biomechanics of the femoral component of the Birmingham hip resurfacing arthroplasty were examined using a highly detailed three-dimensional computer model of the hip. Stresses and strains in the proximal femur were compared for the natural femur and for the femur resurfaced with the Birmingham hip resurfacing. A comparison of cemented versus uncemented fixation showed no advantage of either with regard to bone loading. When the Birmingham hip resurfacing femoral component was fixed to bone, proximal femoral stresses and strains were non-physiological. Bone resorption was predicted in the inferomedial and superolateral bone within the Birmingham hip resurfacing shell. Resorption was limited to the superolateral region when the stem was not fixed. The increased bone strain observed adjacent to the distal stem should stimulate an increase in bone density at that location. The remodelling of bone seen during revision of failed Birmingham hip resurfacing implants appears to be consistent with the predictions of our finite element analysis.

Arthroplasty, Replacement, Hip↗
PubMed2005

Inter-individual and intra-individual variability in TNF-alpha production by human peripheral blood cells in vitro.

BACKGROUND: Two assays--isolated peripheral blood mononuclear cells (PBMC) and a whole blood assay (WBA)--are commonly used to study TNF-alpha production by an individual in order to distinguish between high and low cytokine producers. We assessed the reliability and reproducibility of these assays. METHODS: The PBMC assays (n=5) were performed weekly over a period of 6 weeks and the WBAs (n=4) weekly over a 4-week period. Polymethylmethacrylate particles (approx. 6 x 10(2) particles/cell) and optimal concentrations of endotoxin (6.25 and 12.5 ng/ml) were used as the stimulatory agents in PBMC and WBAs, respectively. TNF-alpha production was measured by ELISA. RESULTS: There was a high degree of both intra- and inter-individual variability of TNF-alpha secretion, with unpredictable changes in the amount of the cytokine produced by cells from the same donor. This variability could not be eliminated by correcting for cell numbers. CONCLUSION: The PBMC and WBA models of TNF-alpha production by human peripheral blood cells cannot be used for the evaluation of inter-individual variability in cytokine secretion due to the high intra-individual variability observed. In the case of PBMC this is partly due to differences in the confluency of the cells between individuals.

Adult↗
PubMed2005

Effect of carbonate substitution on the ultrastructural characteristics of hydroxyapatite implants.

Carbonate ion substitution has been shown to be beneficial for increasing the amount of in vivo osseointegration to hydroxyapatite (HA). Nevertheless, mechanisms by which carbonate ions increase in vivo bioactivity are not fully understood. Sintered granules of HA and carbonate-substituted hydroxyapatite (CHA) were implanted for 6 and 12 weeks in an ovine model. Samples containing the bone-implant interface were prepared for transmission electron microscopy (TEM) and TEM was used to compare the in vivo reactivity of sintered granules of HA and CHA. The current findings demonstrated that CHA (1.2 and 2.05 wt.%) is more soluble than pure HA in vivo. More dissolution was observed from the CHA, at the bone-implant interface and within the implant, when compared to pure HA. A less crystalline phase was formed between the 2.05 wt.% CHA and bone at 12 weeks in vivo. Bone surrounding both the pure HA and 1.2 wt.% CHA was relatively disorganised at 12 weeks. In comparison, bone surrounding the 2.05 wt.% CHA was considerably more organised and in many regions collagen fibrils were present. Despite increased quality of bone surrounding 2.05 wt.% CHA, compared to 1.2 wt.% CHA, the amount of dissolution from both materials was similar.

Animals↗
PubMed2005

Novel deposition of nano-sized silicon substituted hydroxyapatite by electrostatic spraying.

Suspensions containing nano-sized silicon substituted hydroxyaptite (nSiHA) particles were produced and processed for electrostatic spray deposition. No secondary phases were detected by X-ray diffraction, which indicated that the nSiHA was phase pure. Electrostatic spraying of nSiHA in cone-jet mode was achieved at flow rate of 10(-9) m3s(-1) with an applied voltage between the needle and the ring-shaped ground electrode set at 6 to 8 kV. Micrometer- and submicrometer-scaled islands of nSiHA have been deposited on glass and titanium substrates. The surface roughness of such nHA and nSiHA islands was in the range 60 to 80 nm, as measured from atomic force microscopy in tapping mode. The growth of primary human osteoblast (HOB) cells on the nSiHA deposited substrates increased with time during the 4 days of culture, and the increase was related with the Si content in substituted HA, indicating that nSiHA was able to promote and support the growth of HOB cells. Scanning electron microscopy (SEM) revealed that extracellular matrix (ECM) produced by the HOB cells on these nSiHA deposits was well organized. In addition, the presence of Ca and P containing nodules in the ECM were also confirmed by Energy Dispersive X-ray (EDX) analysis, indicating early signs of calcification fronts. The results showed that nSiHA produced by electrostatic spray deposition was able to promote the attachment and the growth of HOB cells. Therefore, electrostatic spray deposition offers great potential for the creation of bioactive surfaces to provide improved interfacial bonding with host tissues.

Cell Adhesion↗
PubMed2005

In vivo assessment of hydroxyapatite and silicate-substituted hydroxyapatite granules using an ovine defect model.

Phase pure hydroxyapatite (HA) and two silicate-substituted hydroxyapatites (0.8 and 1.5 wt% Si, or 2.6 and 4.9 wt% SiO4) were prepared by aqueous precipitation methods. The filter-cakes of HA and silicate-substituted hydroxyapatite (SiHA) compositions were processed into granules 1.0-2.0 mm in diameter and sintered at 1200 degrees C for 2 h. The sintered granules underwent full structural characterisation, prior to assessment in an ovine defect model by implantation for a period of 6 and 12 weeks. The results indicate that HA and SiHA implants were well accepted by the host tissue, with no evidence of inflammation. New bone formation was observed directly on the surfaces and in the spaces between the granular implants. Quantitative histomorphometry as determined by the percentage of bone ingrowth and bone coverage for both SiHA implant compositions was significantly greater than that for phase pure HA. These findings indicate that the in vivo bioactivity of hydroxyapatite was significantly improved by the incorporation of silicate ions into the HA structure, making SiHA ceramics attractive alternatives to conventional HA materials for use as bone graft substitute ceramics.

Animals↗
PubMed2005

Five-year clinical, radiological and postmortem results of the Cambridge Cup in patients with displaced fractures of the neck of the femur.

The Cambridge Cup has been designed to replace the horseshoe-shaped articular cartilage of the acetabulum and the underlying subchondral bone. It is intended to provide physiological loading with minimal resection of healthy bone. The cup has been used in 50 women with displaced, subcapital fractures of the neck of the femur. In 24 cases, the cup was coated with hydroxyapatite. In 26, the coating was removed before implantation in order to simulate the effect of long-term resorption. The mean Barthel index and the Charnley-modified Merle d'Aubigné scores recovered to their levels before fracture. We reviewed 30 women at two years, 21 were asymptomatic and nine reported minimal pain. The mean scores deteriorated slightly after five years reflecting the comorbidity of advancing age. Patients with the hydroxyapatite-coated components remained asymptomatic, with no wear or loosening. The uncoated components migrated after four years and three required revision. This trial shows good early results using a novel, hydroxyapatite-coated, physiological acetabular component.

Acetabulum↗
PubMed2004

Osteoclastic cortical erosion as a determinant of subperiosteal osteoblastic bone formation in the femoral neck's response to BMU imbalance. Effects of stance-related loading and hip fracture.

Femoral neck fractures have previously been shown to be associated with increased cortical and endocortical remodeling, reduced wall thickness of endocortical packets and cortical porosity. Femoral neck width is associated positively with history of lifetime physical activity; so we hypothesized that exposure to mechanical loading may influence the subperiosteal osteoblastic response to the weakening effect of intracortical bone resorption. In 21 femoral neck biopsies from female subjects (13 with hip fracture), there was a positive association between osteoblastic periosteal alkaline phosphatase expression shown in frozen sections and the percentage of cortical canals internal to the subperiosteal surface showing evidence of osteoclastic erosion (Goldner's stain; p =0.03). This was stronger in the plane of locomotor loading and particularly strong in the inferior (compression) cortex ( p =0.002). In 35 cases and 23 age/gender-matched postmortem controls, osteoid-bearing cortical canals (%) were significantly elevated in the fracture cases compared with the controls within the anterior region. There was also a significant correlation between cortical and endocortical %OS/BS (percentage osteoid surface to bone surface) (fracture, n =12; control, n =12) over the whole biopsy ( p =0.041). Generally, these associations of intracortical with endocortical remodeling were consistent with both envelopes being regulated by common processes. These results support the concept that the slow growth of femoral neck width by subperiosteal apposition of bone occurs directly or, otherwise, in response to the weakening of the cortex as it is "trabecularized" by imbalance of bone multicellular units (BMU). This process, in turn, depends on cortical thinning and enlargement of canals with the formation of giant, composite osteons, the whole being more marked in cases of future hip fracture.

Aged↗
PubMed2004

Biological evaluation of carbon-fibre-reinforced polybutyleneterephthalate (CFRPBT) employed in a novel acetabular cup.

Polymer composites are potentially useful materials for orthopaedic applications as they can be tailored to closely match the various moduli of bone. The Cambridge epiphyseal cup has been designed using one such material, carbon-fibre-reinforced polybutyleneterephthalate (CFRPBT), so that more of the load can be transferred to bone in order to reduce bone loss around the implant. We have evaluated the suitability of CFRPBT for this application using several standard and custom biological tests, both in vitro and in vivo, and have also started the initial clinical evaluation of the prosthesis. CFRPBT showed no toxicity in bulk form and only minimal toxicity as a particulate. It was non-haemolytic, non-immunogenic and showed no genotoxicity. No adverse responses were seen after in vivo implantation, and the results obtained following 9 months of clinical evaluation have been very encouraging with a good clinical outcome and good bone bonding to the hydroxyapatite-coated CFRPBT.

Acetabulum↗
PubMed2004

The effect of osteogenic growth factors on bone growth into a ceramic filled defect around an implant.

Currently available synthetic bone substitutes perform poorly compared to autograft. It is hoped that by adding osteogenic growth factors to the materials, new bone formation could be increased and the clinical outcome improved. In this study, IGF-1, bFGF and TGFbeta1, alone and in combination, were absorbed onto a carrier of beta-tricalcium phosphate (betaTCP) and implanted into a defect around a hydroxyapatite-coated, stainless steel implant in the proximal tibia of rat in a model of revision arthroplasty. Animals were sacrificed at 6 and 26 weeks for routine histology and histomorphometry and mechanical push out tests. The results show that only bFGF had a significant effect on ceramic resorption. The groups that received bFGF and bFGF in combination with TGFbeta1 had smaller and fewer betaTCP particles remaining in the defect at 6 and 26 weeks. No growth factor combination significantly enhanced new bone formation or the mechanical strength of the implant. These results indicate that, of the growth factors tested, only bFGF had any beneficial effect on the host response to the implant, perhaps by delaying osteoblast differentiation and thereby prolonging osteoclast access to the ceramic.

Animals↗
PubMed2004

In vitro assessment of the biological response to nano-sized hydroxyapatite.

Nano-sized, rod-like hydroxyapatite (nHA) crystals were produced and shown to be phasepure by X-ray diffraction analysis, as no secondary phases were observed. The nHA suspension was electrosprayed onto glass substrates using a novel processing routine to maintain nanocrystals of hydroxyapatite. The biocompatibility of nHAwas determined using human monocyte-derived macrophages and human osteoblast-like (HOB) cell models. The release of lactate dehydrogenase (LDH) from human monocyte-derived macrophages was measured as an indicator of cytotoxicity. The release of the inflammatory cytokine, tumour necrosis factor alpha (TNF-alpha) from cells in the presence of nHA crystallites was used as a measure of the inflammatory response. Although there was some evidence of LDH release from human monocyte-derived macrophages when in contact with high concentrations of nHA crystals, there was no significant release of TNF-alpha. Moreover, nHA-sprayed substrates were able to support the attachment and the growth of HOB cells. These results indicate that nHA crystals may be suitable for intraosseous implantation and offers the potential to formulate enhanced composites for biomedical applications.

Actin Cytoskeleton↗
PubMed2004

Circulating levels of interleukin-6 and its soluble receptor in patients with head injury and fracture.

There is evidence that fractures heal more rapidly in patients with head injury. We measured the circulating level of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) and soluble glycoprotein 130 (sgp130) in serum from patients who had sustained a head injury with and without fracture and compared these with levels found in control subjects. Within 12 hours of injury the serum level of IL-6 was significantly higher in patients with head injury and fracture compared with the control group. Levels of IL-6 were also significantly higher in patients with head injury and fracture compared with fracture only. While there was no significant difference in circulating levels of sIL-6R in the initial samples they were increased one week after surgery in patients with head injury and fracture and with head injury only. In addition, reduced levels of sgp130 in patients with head injury with and without fracture indicated a possible reduction of the inhibitory effect of this protein on the activity of IL-6. Our study suggests that IL-6 may be involved in altered healing of a fracture after head injury.

Adolescent↗
PubMed2004

Bone growth into a ceramic-filled defect around an implant. The response to transforming growth factor beta1.

Synthetic bone substitutes provide an alternative to autograft but do not give equivalent clinical results. Their performance may be enhanced by adding osteogenic growth factors. In this study, TGFbeta1 was absorbed on to a carrier of beta tricalcium phosphate and Gelfoam and used to fill a defect around a tibial implant in a rat model of revision arthoplasty. We added 0.0, 0.02 microg, 0.1 microg or 1.0 microg of TGFbeta1 to the carrier and then implanted it around an hydroxyapatite-coated stainless-steel pin in the proximal tibia of rats. The tibiae were harvested at three, six or 26 weeks and the amount of bone formation and ceramic resorption were assessed. TGFbeta1 had no effect on the amount of bone in the defect, the amount of fluorescent label incorporated or the rate of mineral apposition. The growth factor did not significantly affect the amount of betaTCP remaining in the tissue at any of the time points.

Animals↗
PubMed2003

Isolation of monocytes from human peripheral blood using immuno-affinity expanded-bed adsorption.

A novel technique for the separation of monocytes from human peripheral blood preparations has been developed. The technique is based on the use of expanded-bed adsorption and a solid perfluorocarbon derivatized with avidin or streptavidin for the indirect positive or negative capture of cells labeled with biotinylated monoclonal antibodies. The perfluorocarbon support was prepared and characterized and the contactor design and operating conditions, that enable cells to be selectively isolated, were investigated. Experiments consisted of applying an immunolabeled pulse of 1 x 10(8) peripheral blood mononuclear cells (PBMCs), isolated by density gradient centrifugation, directly onto a refrigerated expanded bed. The major cell types remaining were T-lymphocytes, B-lymphocytes, and monocytes. Monocytes could be positively adsorbed, following labeling with anti-CD14 mAb, with a clearance of up to 89% and a depletion factor of 7.6. They could also be "eluted" using mechanical shear, with a 77% yield of the applied cells at a purity of 90% and >/= 65% viability. Negative isolation of monocytes, following labeling of the other cells present with anti-CD2, CD7, CD16, CD19, and CD56 mAbs, resulted in lymphocyte depletions of up to 81% with a monocyte enrichment factor of 3.8 and purity of 71%. The monocyte viability in the flowthrough was assessed to be > 95%. This combination of expanded-bed adsorption and fluidizable affinity supports shows significant potential for the intensification of cell separations.

Cell Separation↗
PubMed2003

Evidence for bone formation on the external "periosteal" surface of the femoral neck: a comparison of intracapsular hip fracture cases and controls.

Age-related expansion of the external surface of the femoral neck in order to offset generalized bone loss is potentially an important mechanism whereby hip strength and hence resistance to hip fracture is maintained. However, it has been widely assumed that bone formation is precluded from this external interface due to the presence of a synovial membrane associated with the hip joint. In this study we have demonstrated histologically that bone formation does indeed occur on the outer "periosteal" surface of the proximal femoral neck. It was therefore hypothesized that an impairment or reduction in periosteal bone formation might be seen in cases of femoral neck fracture compared with age-matched controls. Qualitative analysis of whole femoral neck samples from female subjects and age- and sex-matched post-mortem controls demonstrated that these groups expressed similar distributions of the bone formation marker, alkaline phosphatase (AP), at the periosteal surface [whole biopsy mean % periosteal AP-positive surface: control=16.0 (range=0.5-43.0), fracture=13.4 (range=1.0-34.6), p=0.44]. In conclusion, despite a wide intersubject variation, bone formation at the femoral neck periosteum is a feature of elderly women even if they have had a hip fracture.

Aged↗
PubMed2003

Increased femoral neck cancellous bone and connectivity in coxarthrosis (hip osteoarthritis).

Patients with coxarthrosis (cOA) have a reduced incidence of intracapsular femoral neck fracture, suggesting that cOA offers protection. The distribution of bone in the femoral neck was compared in cases of coxarthrosis and postmortem controls to assess the possibility that disease-associated changes might contribute to reduced fragility. Whole cross-section femoral neck biopsies were obtained from 17 patients with cOA and 22 age- and sex-matched cadaveric controls. Densitometry was performed using peripheral quantitated computed tomography (pQCT) and histomorphometry on 10-microm plastic-embedded sections. Cortical bone mass was not different between cases and controls (P > 0.23), but cancellous bone mass was increased by 75% in cOA (P = 0.014) and histomorphometric cancellous bone area by 71% (P < 0.0001). This was principally the result of an increase of apparent density (mass/vol) of cancellous bone (+45%, P = 0.001). Whereas cortical porosity was increased in the cases (P < 0.0001), trabecular width was also increased overall in the cases by 52% (P < 0.001), as was cancellous connectivity measured by strut analysis (P < 0.01). Where osteophytic bone was present (n = 9) there was a positive relationship between the amount of osteophyte and the percentage of cancellous area (P < 0.05). Since cancellous bone buttresses and stiffens the cortex so reducing the risk of buckling, the increased cancellous bone mass and connectivity seen in cases of cOA probably explain, at least in part, the ability of patients with cOA to resist intracapsular fracture of the femoral neck during a fall.

Aged↗