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Biomedical subjects

Christina Gretzer

Publications and source records attributed to Christina Gretzer.

7 recordsLinked to original sources

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↗

Inflammatory response to a titanium surface with potential bioactive properties: an in vitro study.

BACKGROUND: The current hard tissue implants research aims to accelerate bone healing by designing surfaces that are bioactive. However, the role of the inflammatory response to these surfaces is so far incompletely described. PURPOSE: The aim of the study was to evaluate early inflammatory response in vitro to a potentially bioactive surface--an anodized surface with Mg ions incorporated (anodized/Mg)--and to compare it to a turned, a blasted, and an anodized surface. MATERIALS AND METHODS: An interferometer was used for topographical characterizations. The disks were incubated with human mononuclear cells. Adherent cells were investigated with respect to number of cells, viability, differentiation, and cytokine production with and without lipopolysaccharide stimulation after 24 and 72 hours. RESULTS: The number of adhered mononuclear cells differed significantly between the different modified surfaces, with the highest number on the anodized surface. However, there were no significant differences in cytokine production and differentiation between the different modified surfaces. The amount of anti-inflammatory mediator interleukin-10 remained over time, while the number of cells and pro-inflammatory cytokine tumor necrosis factor-alpha decreased. The cells were viable on all surfaces, respectively. CONCLUSION: The anodized surfaces with and without Mg ions showed an increased cell adherence, however, otherwise an inflammatory response similar to the turned and blasted surfaces. Furthermore, the potentially bioactive anodized/Mg surface showed a similar response to the TiUnite-like anodized surface despite the former having a surface roughness of a smoother character.

Cell Adhesion↗

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↗

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↗

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↗

Model porous surfaces for systematic studies of material-cell interactions.

A model system for studying cell-surface interactions, based on microfabricated cell culture substrates, has been developed and is described here. Porous surfaces consisting of interconnecting channels with openings of subcellular dimensions are generated on flat, single crystal, silicon substrates. Channel size (width, depth), distribution, and surface coating can be varied independently and used for systematic investigation of how topographical, chemical, and elastic surface properties influence cell or tissue biological responses. Model porous surfaces have been produced by using two different microfabrication methods. Submicron-sized channels with very high depth-to-width aspect ratios (up to 30) have been made by using electron beam lithography and anisotropic reactive ion etching into single-crystal silicon. Another method uses thick-resist photolithography, which can be used to produce channels wider than 1 microm and with depth-to-width aspect ratios below 20 in an epoxy polymer. Preliminary cell culture tests show that fibroblasts bridge 0.8- to 1.8-microm-wide channels with very few exceptions (i.e., a continuous space below the cell-surface interface is created). It has also been shown that variation of channel periodicity significantly affects fibroblast morphology and attachment density. With this model system, it is possible to load the channels with bioactive substances intended to interact with cells at or near the surface in a time-dependent manner.

Biocompatible Materials↗

Acoustics of blood plasma on solid surfaces.

We have quantified surface associated coagulation of human blood plasma with a recently developed methodological system consisting of a Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), a method that measures the weight of adsorbed molecules on surfaces as a function of frequency shifts of a quartz crystal. Further, it measures the damping energy (i.e. viscoelasticity) of the adsorbed layer. Four different surfaces where studied: Heparin (Hep) surface as an active inhibitor of clot formation, titanium (Ti) surfaces that are known to activate the intrinsic pathway, polystyrene (PS) surfaces and poly(urethane urea) (PUUR) surfaces. The experiments were initiated by applying citrated human plasma at the sensor surfaces; calcium was then added toinitiate coagulation. The Hep surfaces showed no apparent indication of clot formation during one hour of incubation at room temperature. However, on Ti surfaces we observed an early and rapid change in both frequency shift and viscoelastic properties of the coagulating plasma. We inhibited the intrinsic pathway activation by using corn trypsin inhibitor (CTI), which is specific for factor FXIIa in the bulk phase, which prolonged the coagulation times for all non-heparinized surfaces. We have also found a peculiar initial plasma protein interaction phenomenon on Ti surfaces. The described methodology would be very efficient for basic studies of surface associated coagulation and as a screening method for new biomaterials.

Acoustics↗