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Biomedical subjects

Peter Thomsen

Publications and source records attributed to Peter Thomsen.

At least 19 recordsLinked to original sources
PubMed2006

The role of whole blood in thrombin generation in contact with various titanium surfaces.

Understanding of the thrombotic response (activation of the intrinsic coagulation system followed by platelet activation) from blood components upon contact with a titanium dental implant is important and not fully understood. The aims of this study were to evaluate: (1) the thrombogenic response of whole blood, platelet-rich plasma (PRP) and platelet-poor plasma (PPP) in contact with a highly thrombogenic surface as titanium, (2) the thrombogenic response of clinically used surfaces as hydroxyapatite (HA), machined titanium (mTi), TiO2 grit-blasted titanium (TiOB) and fluoride ion-modified grit-blasted titanium (TiOB-F). An in vitro slide chamber model, furnished with heparin, was used in which whole blood, PRP or PPP came in contact with slides of the test surfaces. After incubation (60 min rotation at 22 rpm in a 37 degrees C water bath), blood/plasma was mixed with EDTA or citrate, further centrifuged at +4 degrees C (2200 g at 10 min). Finally, plasma was collected pending analysis. Whole blood in contact with Ti alloy resulted in the binding of platelets to the material surface and in the generation of thrombin-antithrombin (TAT) complexes. With whole blood TAT levels increased 1000-fold compared with PRP and PPP, in which both almost no increase of TAT could be detected. In addition, the platelet activation showed a similar pattern with a 15-fold higher release of beta-TG in whole blood. In the in vitro chamber model with the clinically relevant materials, the fluoride-modified surface (TiOB-F) showed pronounced TAT generation compared with TiOB, mTi and HA. Similar results were achieved for platelet consumption and activation markers of the intrinsic coagulation system. Taken together these results implicate first that whole blood is necessary for sufficient thrombin generation and platelet activation during placement of implants. Second, a fluoride ion modification seems to augment the thrombogenic properties of titanium.

Biocompatible Materials↗
PubMed2006

Aseptic loosening, not only a question of wear: a review of different theories.

Today, aseptic loosening is the most common cause of revision of major arthroplasties. Aseptic loosening accounts for more than two-thirds of hip revisions and almost one-half of knee revisions in Sweden. Several theories on the cause of aseptic loosening have been proposed. Most of these theories, however, are based on empiric observations, experimental animal models or anecdotal cases. In this review, we discuss the most common theories concerning aseptic loosening. It emerges from this review that aseptic loosening has a multifactorial etiology and cannot be explained by a single theory.

Animals↗
PubMed2006

The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials.

The inflammatory and fibrous responses in a subcutaneous rat model were evaluated around degradable polyurethane urea (PUUR; Artelon), with titanium and tissue culture polystyrene (PS) discs having different surface chemical properties but similar surface topography. Cytokines, viability, cellular response, differentiation of cells and fibrous capsule formation and vascularization was investigated after 1, 7 and 21 days of implantation. The exudates retrieved from the pockets were analysed with respect to the total cell numbers, the proportions of cell types, the differentiation of monocytes/macrophages (ED1, ED2), the DNA content and the viability (LD, Trypan blue). Tumour necrosis factor alpha ((h)TNF-alpha) and interleukin-10 ((h)IL-10) were quantified by ELISA. The number of blood vessels, blood vessel luminal area, blood vessel distribution and the fibrous capsule thickness were analysed. The highest number of cells in the exudates around all implants was detected during the early phase of healing (1-7 days). The proportion of ED2-positive cells in the exudates increased from 2-8% at 1 day to 43-56% at 21 days. The levels of TNF-alpha were low with a decrease at 7 days. After 21 days high amounts of IL-10 in the exudates were detected, in particular around PUUR. This study shows that the transition from inflammation to repair (1-21 days) around PUUR, Ti and PS materials was characterized by a decrease in inflammatory cell influx, an increasing proportion of ED2-expressing macrophages, a biphasic TNF-alpha secretion, an increase of IL-10 and a fibrous capsule formation similar to all materials tested.

Animals↗
PubMed2005

Surface-directed capillary system; theory, experiments and applications.

We present a capillary flow system for liquid transport in microsystems. Our simple microfluidic system consists of two planar parallel surfaces, separated by spacers. One of the surfaces is entirely hydrophobic, the other mainly hydrophobic, but with hydrophilic pathways defined on it by photolithographic means. By controlling the wetting properties of the surfaces in this manner, the liquid can be confined to certain areas defined by the hydrophilic pathways. This technique eliminates the need for alignment of the two surfaces. Patterned plasma-polymerized hexafluoropropene constitutes the hydrophobic areas, whereas the untreated glass surface constitutes the hydrophilic pathways. We developed a theoretical model of the capillary flow and obtained analytical solutions which are in good agreement with the experimental results. The capillarity-driven microflow system was also used to pattern and immobilize biological material on planar substrates: well-defined 200 microm wide strips of human cells (HeLa) and fluorescence labelled proteins (fluorescein isothiocyanate-labelled bovine serum albumin, i.e., FITC-BSA) were fabricated using the capillary flow system presented here.

Adsorption↗
PubMed2005

In vivo cytokine secretion and NF-kappaB activation around titanium and copper implants.

The early biological response at titanium (Ti), copper (Cu)-coated Ti and sham sites was evaluated in an in vivo rat model. Material surface chemical and topographical properties were characterized using Auger electron spectroscopy, energy dispersive X-ray spectroscopy and interferometry, respectively. The number of leukocytes, cell types and cell viability (release of lactate dehydrogenase) were determined in the implant-interface exudate. The contents of activated nuclear transcription factor NF-kappaB, interleukin-6 (IL-6) and interleukin-10 (IL-10) were determined by enzyme linked immunosorbent assay. An increase in the number of leukocytes, in particular, polymorphonuclear leukocytes, was observed between 12 and 48 h around Cu. A marked decrease of exudate cell viability was found around Cu after 48 h. The total amounts of activated NF-kappaB after 12 h was highest in Ti exudates whereas after 48 h the highest amount of NF-kappaB was detected around Cu. The levels of cytokine IL-6 were consistently high around Cu at both time periods. No differences in IL-10 contents were detected, irrespective of material/sham and time. The results show that materials with different toxicity grades (titanium with low and copper with high toxicity) exhibit early differences in the activation of NF-kappaB, extracellular expression and secretion of mediators, causing major differences in inflammatory cell accumulation and death in vivo.

Animals↗
PubMed2005

Monocyte viability on titanium and copper coated titanium.

The role of apoptosis/cell death in the inflammatory response at the implanted materials is unexplored. Two surfaces with different cytotoxic potential and in vivo outcomes, titanium (Ti) and copper (Cu) were incubated in vitro with human monocytes and studied using a method to discriminate apoptotic and necrotic cells (Annexin V/PI staining). Further, staurosporine, a potent inducer of apoptosis, was added to the surface adherent monocytes. Lactate dehydrogenase (a marker of cell membrane injury) and TNF-alpha and IL-10, cytokines, previously suggested to play a major role in the monocyte apoptosis, were assayed in the culture medium. The results demonstrated that Ti surfaces displayed enhanced monocyte survival and production of IL-10 and TNF-alpha. Cu adherent cells exhibited apoptotic signs as early as 1h after incubation. In contrast to Ti, after 48 h the predominance of apoptotic cells switched to apoptotic/necrotic cells on Cu surfaces. Staurosporine treatment of Ti adherent cells mediated similar type of cell death. LDH and cytokine contents were low around Cu surfaces, partly explained by interference between Cu ions and LDH and cytokines. This study suggests that material properties rapidly influence the onset of human monocyte apoptosis and progression to late apoptosis/necrosis. Early detection of apoptosis and cell death may be important for the understanding of the biological response to implanted materials.

Annexin A5↗
PubMed2005

The role of implant surface modifications, shape and material on the success of osseointegrated dental implants. A Cochrane systematic review.

We tested the hypothesis of no difference in implant failures between various dental implant types. We searched for all randomised clinical trials comparing different implant types/systems with a follow up of at least one year on four databases. Screening of eligible trials, quality assessment and data extraction were conducted in duplicate. Thirty-one trials were identified. Twelve trials, reporting results of 512 patients, were included. No significant differences were observed for implant failures. There were minor statistically significant differences for peri-implant bone level changes. Turned surfaces had a 20% reduction in risk of being affected by perimplantitis over a 3-year period.

Dental Implantation, Endosseous↗
PubMed2004

Factor XII binding to endothelial cells depends on caveolae.

It is now generally accepted that factor XII (FXII) binds to cellular surfaces in the vascular system. One of the suggested receptors of this binding is the glycosylphosphatidylinositol-anchored urokinase-like plasminogen activator (u-PAR) harbored in caveolae/lipid rafts. However, binding of FXII to human umbilical vein endothelial cells (HUVEC) has never been shown to be localized to these specialized membrane structures. Using microscopical techniques, we here report that FXII binds to specific patches of the HUVEC plasma membrane with a high density of caveolae. Further investigations of FXII binding to caveolae were performed by sucrose density-gradient centrifugations. This showed that the majority of FXII, chemically cross-linked to HUVEC, could be identified in the same fractions of the gradient as caveolin-1, a marker of caveolae, while the majority of u-PAR was identified in noncaveolae lipid rafts. Accordingly, cholesterol-depleted cells were found to bind significantly reduced amounts of FXII. These observations, combined with the presence of a minority of u-PAR in caveolae concomitant with FXII binding, indicate that FXII binding to u-PAR may be secondary and depends upon the structural elements within caveolae. Thus, FXII binding to HUVEC depends on intact caveolae on the cellular surface.

Animals↗
PubMed2004

Enamel matrix derivative for periodontal tissue regeneration in treatment of intrabony defects: a Cochrane systematic review.

We reviewed the literature on the efficacy of enamel matrix derivative (EMD) in comparison with open flap debridement, guided tissue regeneration (GTR), and bone grafting for the treatment of intrabony defects. We searched four major electronic databases for randomized controlled trials (RCTs) with at least one year of follow-up. Several journals were handsearched with no language restrictions. Outcome measures were: tooth loss, changes in probing attachment levels (PAL), pocket depths (PPD), gingival recessions (REC), marginal bone levels on intraoral radiographs, and postoperative infections. Screening of eligible RCTs, assessment of the methodological quality, and data extraction were conducted in duplicate. No difference in tooth loss was observed. A meta-analysis (eight trials) showed that EMD-treated sites displayed statistically significant PAL improvements (mean difference 1.3 mm) and PPD reduction (1 mm) when compared to flap surgery. When EMD was compared to GTR (six trials), GTR showed a statistically significant reduction of PPD (0.6 mm) and increase of REC (0.5 mm). No difference in postoperative infections was observed. No trials compared EMD with bone grafts alone. EMD is able to significantly improve PAL levels and PPD reduction when compared to flap surgery; however, there is no evidence that more teeth could be saved. There was no evidence of important differences between EMD and GTR.

Alveolar Bone Loss↗
PubMed2003

Response of rat osteoblast-like cells to microstructured model surfaces in vitro.

The role of surface microtopography in combination with different surface wettability for rat calvaria cell differentiation was examined. Mineralization and alkaline phosphatase (ALP) activity of rat calvaria cells on flat polydimethylsiloxane (PDMS) or PDMS contained pyramids which were either hydrophilic or hydrophobic were compared. ALP expressing cells were more frequent on hydrophilic PDMS contained pyramids. ALP activity, peaked at day 9, was highest for hydrophilic pyramids followed by hydrophobic pyramids and flat hydrophilic PDMS surfaces. A similar pattern was obtained with respect to mineralized nodules. These observations showed that micro-sized surface features promote differentiation of rat calvaria cells. Further, hydrophilic surfaces are more prone to stimulate differentiation in comparison with hydrophobic surfaces. The results suggest that both material surface chemistry and topography affect osteoblast differentiation.

Alkaline Phosphatase↗
PubMed2003

Resorbable and nonresorbable hydroxyapatite granules as bone graft substitutes in rabbit cortical defects.

BACKGROUND: The use of various synthetic calcium phosphate compositions for the promotion of bone in bone defects is of potential interest because such materials may be tailor made and may bond to bone. There is yet an inadequate knowledge of the role of calcium phosphate composition and resorbability for the bone response. PURPOSE: The aim of the present study was to compare the ability of resorbable versus nonresorbable hydroxyapatite (HA) granules to promote new bone formation in cortical bone defects. Resorbable and nonresorbable HA granules, used as bone graft substitutes, were evaluated after 6 weeks and 3 months in the rabbit tibia. Circular defects (diameter 5.0 mm) were made in both tibias of 18 New Zealand white rabbits. The 36 defects were divided into three groups (six observations per group and time, respectively). The first group was augmented with resorbable HA granules, the second group was augmented with ceramic nonresorbable HA granules, and the third group was left without augmentation (control). The animals were killed after 6 weeks and 3 months, and the tissue was evaluated with light microscopic (LM) morphology and morphometry, scanning electron microscopy (SEM), and energy dispersive x-ray analysis (EDX). RESULTS: After 3 months LM morphometry revealed significantly more newly formed bone in the two HA augmented groups compared with that in the control. A close contact was found between both kinds of HA granules and new bone as viewed with light microscopy and SEM. A relatively slow degradation process was indicated by the small reduction of the total granule area in the cortical defects. However, LM observations showed a change of granule form. Pilot experiments using SEM-EDX indicate that Ca and P contents had decreased in the resorbable HA granules between 6 weeks and 3 months. Further, a higher content of Ca and P was found in the newly formed bone close to granules, in comparison with more distant newly formed bone. CONCLUSIONS: Our results suggest that both resorbable and nonresorbable HA granules promote new bone formation in rabbit cortical defects, which does not occur in control defects.

Absorbable Implants↗
PubMed2003

Short-term bone response to titanium implants coated with thin radiofrequent magnetron-sputtered hydroxyapatite in rabbits.

BACKGROUND: It has been suggested that calcium phosphate (CaP) coatings initiate faster bone growth around implants. A major concern about the viable use of these coatings has been their biologic performance related to the coating characteristics. PURPOSE: The purpose of this study was to investigate the early bone response to micron- and submicron-thick hydroxyapatite (HA) coatings in cortical and trabecular bone. MATERIALS AND METHODS: CaP coatings were manufactured by magnetron sputtering. Heat treatment was subsequently used to increase the crystallinity of the coatings. Coatings were characterized by x-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma optical emission spectroscopy (ICP-OES), and stylus profilometry. Four types of CaP-coated implants were used (0.1 microm and 2.0 microm amorphous; 0.1 microm and 2.0 microm crystalline); uncoated machined commercially pure titanium implants served as controls. Four hundred eighty implants were randomly placed in 60 rabbits. Ten animals were followed up for 1 week, 10 for 3 weeks, and 40 for 6 weeks. The bone response was histomorphometrically evaluated. RESULTS: Coatings with a CaP ratio very close to that of HA were produced. Crystalline coatings significantly improved the early bone-implant contact whereas the amorphous-coated implants behaved similarly to uncoated titanium. CONCLUSIONS: Crystalline CaP coatings 100 nm thick on titanium implants elicited an improved early bone response compared with that of uncoated titanium implants. No further improvement in the bone response was observed with 2 microm coatings.

Animals↗
PubMed2002

Sequestration of epidermal growth factor receptors in non-caveolar lipid rafts inhibits ligand binding.

Cholesterol depletion has been shown to increase mitogen-activated protein kinase activation in response to stimulation with epidermal growth factor (EGF) (Furuchi, T., and Anderson, R. G. W. (1998) J. Biol. Chem. 273, 21099-21104). However, the underlying mechanisms are unknown. We show that cholesterol depletion increases EGF binding, whereas cholesterol loading lowers EGF binding. Based on binding analyses, we demonstrate that the observed changes in EGF binding are caused by alterations in the number of EGF receptors available for ligand binding, whereas the affinity of the receptor for EGF remains unaltered. We also show by immunofluorescence that in unstimulated cells the EGF receptor is localized in non-caveolar lipid rafts containing the ganglioside GM1 and that patching of these rafts by cholera toxin B-chain causes co-patching of EGF receptors. Experiments with solubilization in different detergents at 4 degrees C show that the association of the EGF receptor with these rafts is sensitive to Triton X-100 extraction but insensitive to extraction with another non-ionic detergent, Brij 58. Furthermore, experiments with cholesterol-depleted cells show that the association is cholesterol-dependent. We propose that non-caveolar lipid rafts function as negative regulators of EGF receptor signaling by sequestering a fraction of the EGF receptors in a state inaccessible for ligand binding.

Cell Line↗
PubMed2002

Morphologic and immunohistochemical observations of tissues surrounding retrieved transvenous pacemaker leads.

Immunohistochemical and morphologic techniques were employed to evaluate the tissue response around chronically implanted pacing leads. Seventeen leads were retrieved from 12 patients. Leads were extracted by direct manual traction (1), extraction with sheaths and locking stylets (1), or with by a combination of mechanical tools and Excimer laser sheaths (15). Mean lead implantation time was 5.6 years (range 1-8 years). Frozen sections, 6-8 microm thick, were incubated with antibodies against HLA-DR antigen, endothelial cells, macrophages, T cells, plasma cells, fibrinogen, and interleukin-1beta. Prominent morphologic observations were fibrous encapsulations of the leads. Immunohistochemical analysis revealed a tissue generally devoid of inflammatory and immune cells. The fibrous capsule surrounding the lead was partially or completely covered with a monolayer of CD34 expressing endothelial cells. The results from this study provide useful information in design and material selection for pacemaker leads. Endothelialization of the fibrous encapsulation indicates a functionalization of blood-contacting surfaces around pacemaker materials, thus providing a mechanism for long-term persistence of foreign materials in the blood. The laser method allowed an efficient extraction of pacemaker leads without damage to the studied tissues, as suggested by the presence of immunolabeled cells close to the cut surfaces.

Adult↗
PubMed2002

Ex vivo PMA-induced respiratory burst and TNF-alpha secretion elicited from inflammatory cells on machined and porous blood plasma clot-coated titanium.

The release of inflammatory mediators around implants and normal wounds may differ due to the presence of the solid surface. In this study, machined and sub-micron porous titanium implants with and without a 100 nm thick blood plasma clot were inserted subcutaneously in rat for 3 or 24 h. The cell recruitment to the interfaces, in vivo secretion of TNF-alpha and the ex vivo PMA-induced production of reactive oxygen species were subsequently investigated. The thin plasma clot coating gave rise to an increased ex vivo PMA-stimulated oxygen radical production by implant-associated cells at both implantation times, and an increased cell recruitment at 24 h. The total TNF-alpha secretion was highest at sham sites and plasma clot-coated porous titanium at 24 h. After 24 h, the cell-type pattern in the exudate around the porous plasma-coated implant was more similar to that found at sham sites than that adjacent to the non-coated implants. No differences were observed between the machined Ti and the machined sub-micron porous Ti.

Animals↗
PubMed2002

Caveolae are highly immobile plasma membrane microdomains, which are not involved in constitutive endocytic trafficking.

To investigate whether caveolae are involved in constitutive endocytic trafficking, we expressed N- and C- terminally green fluorescent protein (GFP)-tagged caveolin- 1 fusion proteins in HeLa, A431, and Madin-Darby canine kidney cells. The fusion proteins were shown by immunogold labeling to be sorted correctly to caveolae. By using confocal microscopy and photobleaching techniques, it was found that although intracellular structures labeled with GFP-tagged caveolin were dynamic, GFP-labeled caveolae were very immobile. However, after incubation with methyl- beta-cyclodextrin, distinct caveolae disappeared and the mobility of GFP-tagged caveolin in the plasma membrane increased. Treatment of cells with cytochalasin D caused lateral movement and aggregation of GFP-labeled caveolae. Therefore, both cholesterol and an intact actin cytoskeleton are required for the integrity of GFP-labeled caveolae. Moreover, stimulation with okadaic acid caused increased mobility and internalization of the labeled caveolae. Although the calculated mobile fraction (for t = infinity) of intracellular, GFP-tagged caveolin- associated structures was 70-90%, GFP-labeled caveolae in unstimulated cells had a mobile fraction of <20%, a value comparable to that previously reported for E-cadherin in junctional complexes. We therefore conclude that caveolae are not involved in constitutive endocytosis but represent a highly stable plasma membrane compartment anchored by the actin cytoskeleton.

Animals↗