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Biomedical subjects

S B Doty

Publications and source records attributed to S B Doty.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of proteoglycan modification on mineral formation in a differentiating chick limb-bud mesenchymal cell culture system.

In the presence of 4 mM inorganic phosphate, differentiating chick limb-bud mesenchymal cells plated in micromass cultures form a mineralized matrix resembling that of chick calcified cartilage. To test the hypothesis that cartilage proteoglycans are inhibitors of cell mediated mineralization, the synthesis, content, and turnover of proteoglycans were altered in this system, and the extent of mineralization and properties of the mineral crystals examined. In all cases where the proteoglycan synthesis or proteoglycans present were modified to provide fewer or smaller molecules, mineralization was enhanced. Specifically, when proteoglycan synthesis was blocked by treatment with 10(-10) M retinoic acid, extensive mineral deposition occurred on a matrix devoid of both proteoglycans and cartilage nodules. The crystals, which formed rapidly, were relatively large in size based on analysis by X-ray diffraction or FT-1R microspectroscopy, and were more abundant than in controls. When 2.5 or 5 mM xylosides were used to cause the synthesis of smaller proteoglycans, the extent of mineral accretion was also increased relative to controls; however, the matrix was less affected, and the extent of mineral deposition and the size of the crystals were not as markedly altered as in the case of retinoic acid. Modification of existing proteoglycans by either chondroinase ABC or hyaluronidase treatment similarly resulted in increased mineral accretion (based on 45Ca uptake or total Ca uptake) relative to cultures in which the proteoglycan content was not manipulated. Crystals were more abundant and larger than in control mineralizing cultures. In contrast, when proteoglycan degradation by metalloproteases was inhibited by metal chelation with o-phenanthroline, the Ca accretion at early time points was increased, but as mineralization progressed, Ca accumulation decreased. These data provide evidence that in this culture system, proteoglycans are inhibitors of mineralization.

Animals↗
PubMed1997

Effects of bone CS-proteoglycans, DS-decorin, and DS-biglycan on hydroxyapatite formation in a gelatin gel.

The small leucine-rich bone proteoglycans, biglycan and decorin, can be purified by chromatography on hydroxyapatite columns, demonstrating their potential affinities for bone apatite. To determine their effects on in vitro apatite formation and growth, a mixture of the chondroitin-sulfate (CS) bone proteoglycans, or purified fractions of the dermatan sulfate (DS) containing proteoglycans, DS-decorin and DS-biglycan obtained from skin and articular cartilage, respectively, were analyzed in a gelatin gel diffusion system in which apatite formation occurs in the absence of proteins in a 3.5 day period. Low concentrations of the bone CS-proteoglycan mixture and low DS-biglycan concentrations (5-25 microg/ml) increased apatite formation relative to proteoglycan-free controls at 3.5 days. The CS-proteoglycan mixture was less effective at 50 microg/ml than at 10 microg/ml. DS-biglycan was similarly most effective at 5-25 microg/ml. At 5 days, when apatite growth and proliferation were assessed, 10 and 50 microg/ml of both CS-bone proteoglycan and DS-biglycan increased mineral yields. DS-decorin, in contrast, had no significant effect on mineral accumulation at any of these concentrations. In seeded growth experiments, 1 and 10 microg/ml CS-proteoglycan and 10 and 50 microg/ml DS-biglycan were significant effective inhibitors of mineral accretion, whereas DS-decorin showed no tendency to inhibit seeded growth. Using molar extinction coefficients to determine concentrations, the binding of DS-biglycan and DS-decorin to apatite (specific surface 54 m2/g) was determined using a Langmuir adsorption isotherm model. DS-biglycan had a greater affinity for apatite than DS-decorin (0.285 ml/micromol versus 0.0098 ml/micromol). DS-biglycan binding was more specific with fewer binding sites (3.5 micromol/m2 compared with 18. 2 micromol/m2 for DS-decorin). Data suggest that of the small proteoglycans, biglycan may play a more significant role than decorin in the regulation of mineralization.

Animals↗
PubMed1997

Characterization of cartilage metabolic response to static and dynamic stress using a mechanical explant test system.

A new mechanical explant test system was used to study the metabolic response (via proteoglycan biosynthesis) of mature, weight-bearing canine articular cartilage subjected to static and dynamic compressive stresses. Stresses ranging from 0.5 to 24 MPa were applied sinusoidally at 1 Hz for intervals of 2-24 h. The explants were loaded in unconfined compression and compared to age-matched unloaded explants. Both static and dynamic compressive stress significantly decreased proteoglycan biosynthesis (range 25-85%) for all loading time intervals. The inhibition was proportional to the applied stress but was independent of loading time. After rehydration upon load removal, the measured water content of the loaded explants was not different from the unloaded explants for all test variables. Autoradiographic and electron microscopic analysis of loaded explants showed viable chondrocytes throughout the matrix. Our results suggest that the decreased metabolic response of cyclically loaded explants may be dominated by the static component (RMS) of the dynamic load. Furthermore, the observed decreased metabolism may be more representative of the in situ tissue response than that of unloaded explants, in which we found an increasing rate of metabolism for up to 6 days after explant removal.

Animals↗
PubMed1996

An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction.

30 years ago, investigations into the molecular basis of the delayed-type hypersensitivity reaction (DTH) provided evidence for the first lymphokine activity: a lymphocyte-derived mediator called macrophage migration inhibitory factor (MIF), which inhibited the random migration of peritoneal macrophages. Despite the long-standing association of MIF with the DTH reaction and the cloning of a human protein with macrophage migration inhibitory activity, the precise role of MIF in this classic cell-mediated immune response has remained undefined. This situation has been further complicated by the fact that two other cytokines, interferon gamma and IL-4, similarly inhibit macrophage migration and by the identification of mitogenic contaminants in some preparations of cloned human MIF. Using recently developed molecular probes for mouse MIF, we have examined the role of this protein in a classical model of DTH, the tuberculin reaction in mice. Both MIF messenger RNA and protein were expressed prominently in DTH lesions, as assessed by reverse transcription polymerase chain reaction, in situ hybridization, and immunostaining with anti-MIF antibody. The predominant cellular origin of MIF appeared to be the monocyte/macrophage, a cell type identified recently to be a major source of MIF release in vivo. The administration of neutralizing anti-MIF antibodies to mice inhibited significantly the development of DTH, thus affirming the central role of MIF in this classic immunological response.

Animals↗
PubMed1996

The mechanism of beta-glycerophosphate action in mineralizing chick limb-bud mesenchymal cell cultures.

Differentiating chick limb-bud mesenchymal cells plated in micromass culture form a cartilage matrix that can be mineralized in the presence of 4 mM inorganic phosphate (Pi), and 1 mM calcium. Previous studies showed that when beta-glycerophosphate (beta GP) is used in place of Pi, the mineral crystals formed are larger and differ in distribution. The present study shows that the difference in distribution is not associated with alterations in cell proliferation, protein synthesis, or with collagen, proteoglycan core protein, or alkaline phosphatase gene expression. Cultures with 2.5, 5, and 10 mM beta GP did show different levels of alkaline phosphatase activity, and in the presence of low (0.3 mM) Ca had different Pi contents (4, 6 and 9 mM, respectively), indicating that the increase in CaxP product may in part be responsible for the altered pattern of mineralization. However, cultures with beta GP in which alkaline phosphatase activity was inhibited with levamisole still had an altered mineral distribution as revealed by Fourier transform-infrared (FT-IR) microspectroscopy. The presence of a casein kinase II-like activity in the mineralizing cultures, the ability of specific inhibitors of this enzyme to block mineralization, and the known ability of beta GP to block phosphoprotein phosphatase activity suggests that altered patterns of matrix protein phosphorylation may influence mineral deposition in these cultures.

Alkaline Phosphatase↗
PubMed1996

Viable cells are a requirement for in vitro cartilage calcification.

It is a common belief that chondrocyte death must precede calcification in the growth plate. To challenge this dogma, cell devitalization was induced in an in vitro model that mimics in situ cartilage calcification. Chick limb-bud mesenchymal cells, plated in micromass culture, differentiate to form a cartilaginous matrix which mineralizes in the presence of inorganic or organic phosphate. The mineral formed resembles physiologic mineral in crystal size, composition, and distribution. Killing cells by water lysis, ethanol fixation, freeze-thawing, trypsinization, or impairing their function by oligomycin treatment prior to the time at which mineralization commenced, prevented mineral deposition. In contrast, devitalizing cells by any of these techniques after mineralization commenced resulted in dystrophic calcification (excessive, randomly distributed mineral of larger than physiologic crystal size). Based on analyses of 45Ca uptake, FT-IR microscopy, X-ray diffraction, and transmission electron microscopy, it is concluded that the presence of viable cells is obligatory for physiologic cartilage calcification in the differentiating chick limb-bud mesenchymal cell culture system.

Animals↗
PubMed1996

Fibronectin regulates calvarial osteoblast differentiation.

The secretion of fibronectin by differentiating osteoblasts and its accumulation at sites of osteogenesis suggest that fibronectin participates in bone formation. To test this directly, we determined whether fibronectin-cell interactions regulate progressive differentiation of cultured fetal rat calvarial osteoblasts. Spatial distributions of alpha 5 integrin subunit, fibronectin, osteopontin (bone sialoprotein I) and osteocalcin (bone Gla-protein) were similar in fetal rat calvaria and mineralized, bone-like nodules formed by cultured osteoblasts. Addition of anti-fibronectin antibodies to cultures at confluence reduced subsequent formation of nodules to less than 10% of control values, showing that fibronectin is required for normal nodule morphogenesis. Anti-fibronectin antibodies selectively inhibited steady-state expression of mRNA for genes associated with osteoblast differentiation; mRNA levels for alkaline phosphatase and osteocalcin were suppressed, whereas fibronectin, type I collagen and osteopontin were unaffected. To identify functionally relevant domains of fibronectin, we treated cells with soluble fibronectin fragments and peptides. Cell-binding fibronectin fragments (type III repeats 6-10) containing the Arg-Gly-Asp (RGD) sequence blocked both nodule initiation and maturation, whether or not they contained a functional synergy site. In contrast, addition of the RGD-containing peptide GRGDSPK alone did not inhibit nodule initiation, although it did block nodule maturation. Thus, in addition to the RGD sequence, other features of the large cell-binding fragments contribute to the full osteogenic effects of fibronectin. Nodule formation and osteoblast differentiation resumed after anti-fibronectin antibodies or GRGDSPK peptides were omitted from the media, showing that the inhibition was reversible and the treatments were not cytotoxic. Outside the central cell-binding domain, peptides from the IIICS region and antibodies to the N terminus did not inhibit nodule formation. We conclude that osteoblasts interact with the central cell-binding domain of endogenously produced fibronectin during early stages of differentiation, and that these interactions regulate both normal morphogenesis and gene expression.

Amino Acid Sequence↗
PubMed1995

Diminished material properties and altered bone structure in rat femora during pregnancy.

Pregnancy and lactation are known to cause structural and mechanical changes in bone, but the effects of pregnancy alone have not been evaluated thoroughly. This study used radiographic measurements, torsion testing, mineral analyses, and histological evaluation to determine whether there are changes in bone material and geometric properties during pregnancy in the growing rat, as implied by earlier biochemical and histological studies. The bones of pregnant 9 to 12-week-old rats and controls that were not pregnant and were matched by age (but not weight) were evaluated at times corresponding to 5, 10, 15, and 20 days of the 23-day gestation period to address the following questions: (a) How is the growth of whole bone affected by pregnancy in the growing rat (as determined by radiographic analyses)? (b) How are the mechanical properties (structural and material) of whole bone affected by pregnancy (as assessed by torsion testing)? (c) Are there changes in the characteristics of bone mineral during pregnancy (as determined by measurement of mineral content and x-ray diffraction analyses)? and (d) Are there detectable morphological or ultrastructural differences between the bones of pregnant and control rats (as assessed by analyses based on histology and back-scattered electron imaging)? The presence of statistically significant differences in this study was determined initially on the basis of a two-factor analysis of variance. In general, significant differences were noted only at late gestation (day 20), when the bones were longer and had a greater outer radius and cortical thickness; this indicates that more growth occurred during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Immunolocalization and expression of bone morphogenetic proteins 2 and 4 in fracture healing.

Recently, it has become increasingly evident that fracture healing involves a complex interaction of many local and systemic regulatory factors. The roles of some of these growth factors have been described; however, little is understood about the presence of the bone morphogenetic proteins in fracture repair, despite the fact that they are the most potent osteoinductive proteins known. This study defines and characterizes the physiologic presence, localization, and chronology of the bone morphogenetic proteins in fracture healing with an established rat fracture healing model. With use of a recently developed monoclonal antibody against bone morphogenetic proteins 2 and 4 developed with standard avidin-biotin complex/immunoperoxidase protocols, frozen undecalcified fracture calluses were analyzed semiquantitatively for the percentage of various types of fracture cells staining positively. During the early stages of fracture healing, only a minimum number of primitive cells stained positively in the fracture callus. As the process of endochondral ossification proceeded, the presence of bone morphogenetic proteins 2 and 4 increased dramatically, especially in the primitive mesenchymal and chondrocytic cells. While the cartilaginous component of the callus matured with a concomitant decrease in the number of primitive cells, there was a concomitant decrease in both the intensity and the number of positively staining cells. As osteoblasts started to lay down woven bone on the chondroid matrix, these osteoblastic cells exhibited strong positive staining. The intensity of this staining decreased, however, as lamellar bone replaced the primitive woven bone. A similar observation was noted for the areas of the callus undergoing intramembranous ossification. Initially, within several days after the fracture, periosteal cells and osteoblasts exhibited intense staining for bone morphogenetic proteins 2 and 4. As the woven bone was replaced with mature lamellar bone, this staining decreased. These data, and the awareness of the strong osteoinductive capacities of bone morphogenetic protein, suggest that bone morphogenetic proteins 2 and 4 are important regulators of cell differentiation during fracture repair.

Animals↗
PubMed1995

Pathophysiology of immobilization osteoporosis.

The reduction of gravity-related forces on the skeleton creates a type of osteoporosis that is unique because its severity is dependent on the mechanical stress bearing function of the skeleton as well as the length of time that the forces are absent or reduced. Bones that bear weight under normal conditions are more affected than bones that normally do not bear weight. The cytokine environment and the cells in the affected bones are altered in time so that stem cells produce fewer new cells and the differentiated cells tend to be less active. These alterations in the local environment of the affected parts appear to resemble those of age- and disease-associated systemic forms of osteoporosis. The osteoporosis produced as a result of the loss of normal activity however, appears to be at least partially reversible through remobilization, strenuous exercise, and--possibly in the future--cytokine therapy.

Animals↗
PubMed1994

Adenosine 5'-triphosphate promotes mineralization in differentiating chick limb-bud mesenchymal cell cultures.

When chick limb-bud mesenchymal cells are plated in micromass culture, they differentiate to form a mineralizable cartilage matrix. Previous studies have demonstrated that, when the total inorganic phosphate concentration of the medium is adjusted to 3-4 mM by adding inorganic phosphate to the basal medium, the mineralized matrix formed resembles that of chick calcified cartilage in ovo. When the high-energy phosphates adenosine 5'-triphosphate (ATP) or creatine phosphate are used as supplements in place of inorganic phosphate, the mineralized matrix as analyzed by electron microscopy and Fourier transform infrared microscopy is also similar to that in ovo. This is in marked contrast to the mineralized matrix formed in the presence of 2.5-5 mM beta-glycerophosphate, where mineral deposition is random and mineral crystal sizes in general are larger. This is also in contrast to the known ability of ATP to inhibit mineral deposition in solution in the absence of cells. In the differentiating mesenchymal cell culture system, ATP does not alter the rate of cell proliferation (DNA content), the rate of matrix synthesis (3H-leucine uptake), the mean crystallite length, or the rate of mineral deposition (45Ca uptake) when contrasted with cultures supplemented with inorganic phosphate. However, ATP does increase the mineral to matrix ratio, especially around the edge of the culture, where a type I collagen matrix is presented. It is suggested that ATP promotes mineral deposition by providing a high-energy phosphate source, which may be used to phosphorylate extracellular matrix proteins and to regulate calcium flux through cell membranes.

Adenosine Triphosphate↗
PubMed1994

Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage.

Loss of bone mass during periods of skeletal unloading remains an important clinical problem. To determine the extent to which resorption contributes to the relative loss of bone during skeletal unloading of the growing rat and to explore potential means of preventing such bone loss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal increase in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone resorption was also modestly stimulated. Alendronate not only prevented the relative loss of skeletal mass during unloading but led to a dramatic increase in calcified tissue in the proximal tibia compared with the vehicle-treated unloaded or normally loaded controls. Bone formation, however, assessed both by tetracycline labeling and by [3H]proline and 45Ca incorporation, was suppressed by alendronate treatment and further decreased by skeletal unloading. Total osteoclast number increased in alendronate-treated animals, but values were similar to those in controls when corrected for the increased bone area. However, the osteoclasts had poorly developed brush borders and appeared not to engage the bone surface when examined at the ultrastructural level. We conclude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so primarily by inhibiting the resorption of the primary and secondary spongiosa, leading to altered bone modeling in the metaphysis.

Alendronate↗
PubMed1993

Gallium nitrate inhibits alkaline phosphatase activity in a differentiating mesenchymal cell culture.

The effect of gallium nitrate on alkaline phosphatase activity in a differentiating chick limb-bud mesenchymal cell culture was monitored in order to gain insight into the observation that rachitic rats treated with gallium nitrate failed to show the expected increase in serum alkaline phosphatase activity. Cultures maintained in media containing 15 microM gallium nitrate showed drastically decreased alkaline phosphatase activities in the absence of significant alterations in total protein synthesis and DNA content. However, addition of 15 microM gallium nitrate to cultures 18 h before assay for alkaline phosphatase activity had little effect. At the light microscopic and electron microscopic level, gallium-treated cultures differed morphologically from gallium-free cultures: with gallium present, there were fewer hypertrophic chondrocytes and cartilage nodules were flatter and further apart. Because of altered morphology, staining with an antibody against chick cartilage alkaline phosphatase appeared less extensive; however, all nodules stained equivalently relative to gallium-free controls. Histochemical staining for alkaline phosphatase activity was negative in gallium-treated cultures, demonstrating that the alkaline phosphatase protein present was not active. The defective alkaline phosphatase activity in cultures maintained in the presence of gallium was also evidenced when cultures were supplemented with the alkaline phosphatase substrate, beta-glycerophosphate (beta GP). The data presented suggest that gallium inhibits alkaline phosphatase activity in this culture system and that gallium causes alterations in the differentiation of mesenchymal cells into hypertrophic chondrocytes.

Alkaline Phosphatase↗
PubMed1993

Osteopontin-hydroxyapatite interactions in vitro: inhibition of hydroxyapatite formation and growth in a gelatin-gel.

Osteopontin is a phosphorylated bone matrix sialoprotein, postulated to play a regulatory role in biomineralization. The effects of a crude preparation of rat bone osteopontin and a more highly purified bovine bone osteopontin were evaluated using a gel diffusion system to measure effects of 0.1-100 micrograms/ml of this matrix protein on hydroxyapatite formation and crystal proliferation. Bovine osteopontin at concentrations greater than 25 micrograms/ml inhibited both hydroxyapatite formation and growth in a dose-dependent manner. Osteopontin at concentrations lower than 25 micrograms/ml had no detectable effect on the amount of mineral accumulated in experiments with and without pre-formed hydroxyapatite seed crystals either when initial mineral deposition was assessed at 3.5 days, or when mineral formation and growth were assessed at 5 days. There was a statistically significant dose-dependent decrease in crystal length at all concentrations tested. The rat osteopontin preparation had similar inhibitory abilities. Partial dephosphorylation of bovine osteopontin with alkaline phosphatase removed its inhibitory ability, and reduced its ability to bind calcium. The affinity of bovine osteopontin for hydroxyapatite was determined based on a Langmuir adsorption isotherm, with values of K (binding affinity) and N (number of binding sites) being 0.026 ml/microgram and 1084 micrograms/m2, respectively. The data suggest that, in this system, osteopontin is an effective inhibitor of hydroxyapatite formation and growth due to its affinity for the hydroxyapatite crystals. In this system, osteopontin, distinct from other phosphoproteins which both promote and inhibit hydroxyapatite deposition, did not enhance mineral formation at any concentration tested.

Animals↗
PubMed1993

Studies of the mechanism by which the mechanical failure of polymethylmethacrylate leads to bone resorption.

The purpose of this study was to examine the relationship between the mechanical failure of polymethylmethacrylate and bone resorption at the bone-cement interface of a prosthesis. Evaluation of tissue that had been retrieved from the cement-bone interface of eighteen femoral components of total hip prostheses that were loose without associated infection revealed that a critical factor associated with bone resorption was the presence of particles that were small enough (one to twelve micrometers) to be phagocytized by macrophages. To study this phenomenon in vitro, macrophages in tissue culture were exposed to three preparations of polymethylmethacrylate cement. A novel method of cement preparation was used with control for solid and soluble contaminants, which provided a sensitive and specific technique for the determination of which mediators were released from the macrophages. Electron microscopy demonstrated phagocytosis of particles of less than twelve micrometers in size, regardless of the type of cement preparation. Exposure to all three cement preparations resulted in toxicity, as reflected by inhibition of 3H-thymidine incorporation. Exposure also led to increased release of tumor necrosis factor, but none of the three preparations resulted in release of prostaglandin E2. Division of the cement preparations into two groups on the basis of the size of the particles demonstrated that exposure to particles that were small enough to be phagocytized led to inhibition of 3H-thymidine incorporation and release of tumor necrosis factor, while exposure to particles that were too large to be phagocytized did not. Neither exposure to small particles nor exposure to large particles of cement led to release of prostaglandin E2. Our results show that when the mechanical failure of cement produces particles that are small enough to be phagocytized, phagocytosis of the particles results in the increased production of tumor necrosis factor by the macrophages, which may in turn lead to bone resorption and prosthetic loosening. These small particles also decrease 3H-thymidine uptake by the macrophages.

Bone Cements↗
PubMed1993

The pathophysiologic role of fat in dysbaric osteonecrosis.

Dysbaric osteonecrosis (DON) can occur in humans and sheep after a single hyperbaric air exposure with inadequate decompression. The authors hypothesize that DON does not result from primary embolic or compressive effects of nitrogen bubbles on the osseous vasculature, but by secondary injury to the marrow adipose tissue by rapidly expanding nitrogen gas that triggers local, and possibly systemic, intravascular coagulation. A 28-year-old scallop diver remained at a depth of 92 feet in sea water for 4.5 hours on surface-supplied compressed air. Decompression sickness occurred after a no-stop ascent to the surface, and he died 70 minutes later. Autopsy showed multiple gas bubbles, not only within the great vessels, but in the fatty marrow of his femoral and humeral heads. Lipid and platelet aggregates were found on the surface of marrow bubbles. Fibrin-platelet thrombi were detected within dilated venous sinusoids adjacent to bubbles, and in veins, capillaries, and arterioles. Since pulmonary, renal, and intraosseous (subchondral) fat embolism and fibrin thromboses were observed, it is suggested that injured marrow adipocytes can release liquid fat, thromboplastin, and other vasoactive substances, which conceivably can also play a systemic procoagulant role in triggering disseminated intravascular coagulation and additional DON.

Adipose Tissue↗
PubMed1993

Particulate metallic debris in cemented total hip arthroplasty.

Several studies conducted by the authors in the last six years demonstrate that the generation of metallic debris is more severe with titanium alloy than with cobalt-chrome alloy femoral components in cemented total hip arthroplasty (THA). The debris is generated from the articulating surface, particularly if entrapped acrylic debris produces three-body wear, and from the stem surface when the component loosens and abrades against fragmented cement. In selected cases in which the titanium metallic debris is copious, premature failure and severe progressive bone loss occurs. Electron microscopy demonstrates that the particles of metallic debris can be extremely small (a few hundredths of 1 micron). They are phagocytized by the macrophages and transported to the phagolysosomes. In this highly corrosive environment, the very high surface area of the particles may release toxic concentrations of the constituents of the alloy intracellularly, probably leading to progressive cell degeneration and death, with subsequent release of intracellular enzymes and ingested metallic debris. This cycle most likely repeats itself, leading to tissue necrosis. The results presented do not support the use of titanium alloy femoral components for cemented THA, particularly for the articulating surface.

Alloys↗