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PubMed1989

Determination of 3,5,6-trichloro-2-pyridinol levels in the urine of termite control workers using chlorpyrifos.

Chlorpyrifos, an organophosphorus insecticide, has been used to control termites since regulatory measures against the use of chlordanes were taken in September, 1986. We developed an improved gas chromatographic (GC) method for the assay of 3,5,6-trichloro-2-pyridinol (TCP) in the urine to use in the biological monitoring of exposure to chlorpyrifos. Urinary TCP was separated and determined accurately (C.V., 4%) with high sensitivity (detection limit, 10 ng/ml) and recovery (recovery greater than 90%) using a wide bore capillary column (WBC column). The accuracy and precision of the present GC method are satisfactory. The time course of urinary excretion of TCP was followed in workers. The urinary TCP level was low in the off-season and high in the busy season. Variation in the urinary TCP level corresponded to the termite control season and the length of the working period. The urinary TCP level showed a change reciprocal to the variations in the plasma cholinesterase activity. From these results, it is surmised that the urinary TCP level represents the extent of exposure to chlorpyrifos. The decrease in the level of cholinesterase activity is suggested to be due to exposure to chlorpyrifos. Determination of the urinary TCP level by GC using a WBC column is useful in the biological monitoring of chlorpyrifos in termite control workers and potentially has practical application to health care.

Adult↗
PubMed2006

Pyrolusite (beta-MnO2)-mediated, near dry-phase oxidation of 2,4,6-trichlorophenol.

The pyrolusite (beta-MnO2)-mediated oxidation of 2,4,6-trichlorophenol (TCP) under nonaqueous conditions was investigated to assess the potential for abiotic transformations of chlorophenols and their transformation pathways when they are released to soils and the vadose zone. Lower rates of TCP oxidation were found at lower relative humidities, but the rates were still relatively high under near-dry conditions, with 86% of the TCP transformed within 24 h at less than 2% relative humidity. The rates of TCP transformation and soluble manganese formation at less than 2% relative humidity were not affected by atmospheric oxygen content. The manganese oxide-mediated oxidation of TCP resulted in the formation of 2,6-dichloro-1,4-benzoquinone and dimers, including polychlorinated phenoxyphenols and at least one tetrachlorodibenzo-p-dioxin. The products are consistent with the proposed mechanism in which some of the TCP is transformed into trichlorophenoxy radicals that attack TCP and its transformation products. The present results demonstrate that naturally occurring manganese oxides have the potential to oxidize industrial compounds such as TCP; however, the transformation products may be more toxic and persistent than the parent compound.

Chlorophenols↗
PubMed2006

Effect of a hydroxyapatite tricalcium phosphate alloplast on osseous repair in the rat calvarium.

BACKGROUND: Bony defects caused by periodontitis are often treated by regenerative therapy using autografts and/or allografts. Alloplasts, such as hydroxyapatite or ceramics, are also used as osteoconductive materials that serve as a scaffold for new bony ingrowth. The purpose of this study was to determine the effect of hydroxyapatite tricalcium phosphate (HA-TCP) on osseous repair in the rat calvarium. METHODS: Forty-four adult male Harlan Sprague-Dawley rats were assigned to one of four treatment groups: HA-TCP macroporous disk, HA-TCP microporous disk, HA-TCP granules, and demineralized freeze-dried bone (DFDB). The materials were placed into 8-mm calvarial critical-size defects (CSD). Calvariae were harvested at 10 weeks post-surgery and evaluated histomorphometrically. RESULTS: The DFDB group had significantly (P <0.05) more new bone formation (47%) than any other group. The HA-TCP macroporous disk group had significantly (P <0.05) more new bone formation (19.7%) than the HA-TCP microporous disk (8.5%) or HA-TCP granule (6.9%) groups. CONCLUSIONS: The HA-TCP macroporous disk may elicit significant new bone formation due to its rigid space-maintaining scaffold and pore size for vascular ingrowth. It is well tolerated by host tissues and may be a suitable carrier for growth factors.

Animals↗
PubMed2006

Development of beta-tricalcium phosphate/collagen sponge composite for bone regeneration.

Synthetic biomaterials have been developed and used for bone grafting. Here, we developed a biodegradable sponge composite for bone tissue engineering by combining beta-tricalcium phosphate (beta-TCP) and collagen. In addition, we sought to determine the optimal beta-TCP granules/collagen ratio by evaluating and bone formation in vivo. Porous beta-TCP granules were mixed with atelocollagen hydrochloride solution at various ratios--0.02, 0.05, 0.1, and 0.2 g/mL. The resultant mixtures were freeze-dried and subjected to dehydrothermal treatment in vacuo. The final composites obtained were designated beta-TCP/collagen sponge composites (beta-TCP/CS). Through compression testing, it was found that the stress values for beta-TCP/CS (0.2 g/mL) were higher than those of the other three composites over the whole strain range. Histological evaluation at four weeks after implantation revealed that the collagen sponge had degraded and newly formed bone was present on the surface of the beta-TCP granules. At 12 weeks, the beta-TCP granules were completely degraded and remodeling of the lamellar bone was observed.

Animals↗
PubMed1999

Effects of glucose and phenylalanine upon 2,4,6-trichlorophenol degradation by Pseudomonas paucimobilis S37 cells in a no-growth state.

Pseudomonas paucimobilis S37, a strain able to degrade 2,4,6-trichlorophenol (246-TCP), was isolated from an aquatic environment polluted with this compound. The effect of two natural organic compounds on the degradation of 246-TCP by this strain, in a no-growth state, was studied. Bacterial cultures were exposed to 0.1 mM and 0.5 mM of 246-TCP, alone, or in the presence of similar concentrations of glucose, a growth supporting substrate, or phenylalanine, a no-growth supporting compound. The effects on viable counts and 246-TCP degradation were measured. The bacterial culture died with 0.5 mM 246-TCP. This effect was overcome by the presence of glucose or phenylalanine, although no degradation of 246-TCP was detected. At 0.1 mM 246-TCP, the viability was not altered, and cells were able to degrade this compound. Glucose at 0.1 mM increased the degradative activity, but higher levels were inhibitory. Phenylalanine at 0.67 mM or higher concentration was also inhibitory of the 246-TCP degradation.

Biodegradation, Environmental↗
PubMed2001

Determinants of chlorpyrifos exposures and urinary 3,5,6-trichloro-2-pyridinol levels among termiticide applicators.

The exposures and work activities of 41 applicators in North Carolina using chlorpyrifos-containing termiticides were characterized. Personal air and urine samples were collected on multiple days within one week. Detailed information about chemical use, tasks, personal protective equipment and hygiene was recorded. During the 202 applicator-days monitored, 415 treatment jobs were performed. Full-shift chlorpyrifos exposures ranged from <0.048 to 110 microg/m(3) (N=184), with a geometric mean (GM) of 10 microg/m(3). Urinary 3,5,6-trichloro-2-pyridinol (TCP) levels ranged from 9.42 to 1960 microg/g creatinine (N=271) and varied significantly by day of the week (GM range: 169-262 microg/g creatinine). Predictive models for chlorpyrifos air exposure and urinary TCP levels were developed using mixed-effects stepwise linear regression. Determinants of airborne chlorpyrifos exposure included minutes chlorpyrifos applied and enclosed crawl space treated (yes/no). Determinants of TCP levels (depending on the model) included day-of-the-week, the chlorpyrifos air concentration one and two days before urine collection, minutes of chlorpyrifos applied one and two days before urine collection, enclosed crawl space treated (yes/no), and commercial structure treated (time-weighted). Within- and between-worker variability was similar for airborne chlorpyrifos; however, for TCP, between-worker variability exceeded within-worker variability by six times. The elimination half-life of TCP (26.9 h) and possibly the short sampling interval (one week) may explain the low TCP within-worker variability. Applicators' weekly mean ln(TCP levels) and weekly mean ln(chlorpyrifos air concentrations) were highly and positively linearly correlated (r(2)=0.73, P<0.0001). In summary, mixed-effects models were successfully constructed to predict airborne chlorpyrifos exposure and urinary TCP levels.

Adolescent↗
PubMed2003

Evaluation of apatite ceramics containing alpha-tricalcium phosphate by immersion in simulated body fluid.

The purpose of this study was to estimate the availability of alpha-tricalcium phosphate (alpha-TCP) on/in hydroxyapatite (HAP) ceramics for bioactivity as bone-substitute materials by immersion in a simulated body fluid (SBF; Hanks' solution) containing ion concentrations similar to those in human blood plasma. Two alpha-TCP-surface-modified HAP and alpha-TCP-HAP composite materials were prepared by orthophosphoric acid treatment of sintered HAP and controlling the crystal phases of calcium phosphate cement, respectively. After immersion in SBF, the sintered HAP modified on the surface in an approximately 0.2 microm alpha-TCP layer was more effective for the precipitation of carbonated apatites than an approximately 2 microm alpha-TCP layer and HAP-only layer. In the calcium phosphate cements consisting of HAP and alpha-TCP phases, after immersion for 1 week, the specimens precipitated large amounts of apatites having alpha-TCP contents of approximately 25% and 50% in the cement. The results of immersion tests imply the possibility that the alpha-TCP on/in HAP ceramics may be a bioactive agent for bone-substituting HAP materials.

Biomimetic Materials↗
PubMedDate not supplied

Comparative disposition and metabolism of 1,2,3-trichloropropane in rats and mice.

1,2,3-Trichloropropane (TCP) has been used as a solvent and degreasing agent and as an intermediate in pesticide manufacture. TCP is currently the subject of a National Toxicology Program chronic toxicity study. The present study is part of a larger effort to characterize the toxicity of TCP. Following acute oral exposure of male and female F344 rats (30 mg/kg) and male B6C3F1 mice (30 and 60 mg/kg), TCP was rapidly absorbed, metabolized, and excreted. The major route of excretion of TCP was in the urine. By 60 hr postdosing, rats had excreted 50% and mice 65% of the administered dose by this route. Exhalation as 14CO2 and excretion in the feces each accounted for 20% of the total dose in 60 hr rats and 20 and 15%, respectively, in mice. No apparent sex-related differences were observed in the ability of the rats to excrete TCP-derived radioactivity. At 60 hr, TCP-derived radioactivity was most concentrated in the liver, kidney, and forestomach in both rats and male mice. Male mice eliminated TCP-derived radioactivity more rapidly than rats and lower concentrations of radioactivity were found in tissues 60 hr after dosing in mice. Two urinary metabolites were isolated and identified by NMR, mass spectroscopy, and comparison with synthetic standards, as N-acetyl- and S-(3-chloro-2-hydroxypropyl)cysteine. Analyses of the early urine (0-6 hr) showed this mercapturic acid to be the major metabolite in rat urine and was only a minor component in mouse urine. 2-(S-Glutathionyl)malonic acid was identified by NMR and mass spectrometry and by chemical synthesis as the major biliary metabolite in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Investigations on the mechanism of positive inotropic action of (+)-tranylcypromine in isolated guinea-pig atria.

Investigations on the mechanism of the positive inotropic action of (+)-tranylcypromine (TCP) on left, electrically stimulated, isolated guinea-pig atria led to the following results: In contrast to (-)-TCP, the positive inotropic action of (+)-TCP on the guinea-pig atria is not abolished, but only weakened by pretreating animals with reserpine. The positive inotropic effect of indirectly acting sympathomimetics, such as tyramine or methamphetamine, on isolated atria of reserpine pretreated guinea pigs recovers within 15-30 min of incubation with (+)-TCP. The same applies to other inhibitors of MAO-A, such as clorgiline and pargyline as well as selegiline (deprenyl) in higher concentrations. Inhibitors of norepinephrine (noradrenaline) synthesis as alpha-methyl-p-tyrosine and FLA-63 (bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)-disulphide] prevent the positive inotropic action of (+)-TCP on atrial preparations of reserpine pretreated guinea pigs, and abolish the (+)-TCP induced restitution of the effects of tyramine and methamphetamine. A destruction of adrenergic nerves using 6-hydroxydopamine also prevents the positive inotropic action of (+)-TCP. These results suggest that (+)-TCP increases the net neuronal synthesis of catecholamines.

Animals↗
PubMed1982

The effect of tranylcypromine on levels of 6-keto-PGF1 alpha and other prostaglandins in brain and mesentery of the mouse.

Tranylcypromine (TCP), which can inhibit prostacyclin (PGI2) synthesis in vitro, has been shown to facilitate platelet aggregation in damaged cerebral arterioles of the mouse when given intraperitoneally (50 mg/kg) one hour before inducing aggregation. The same dose has no effect on platelet aggregation in damaged mesenteric arterioles. The present experiments used HPLC and GC/MS to analyze PG levels and show that 5 or 50 mg/kg TCP, given intraperitoneally one hour before sacrificing the mouse, moderately reduces the level of 6-keto-PGF1 alpha, the stable metabolite of PGI2, in incubated brain homogenates. This finding supports the hypothesis that TCP's enhancement of platelet aggregation in the brain was affected by a reduction in PGI2 levels. When 500 micrograms/ml TCP was added to the incubate of brain homogenate from mice given 50 mg/kg, PGE2 levels were reduced as well as the levels of 6-keto-PGF1 alpha. In incubated mesentery, the level of 6-keto-PGF1 alpha was also reduced by treating mice with 50 mg/kg TCP. The latter result failed to support the hypothesis that levels of mesenteric 6-keto-PGF1 alpha would be unaltered by TCP in parallel with the inability of TCP to alter platelet aggregation in mesenteric arterioles. Thus our data fails to support an overall hypothesis relating TCP action on platelet aggregation to its inhibitory effect on PGI2 synthesis. At the same time the data do not rule out such a relationship for mouse brain.

Animals↗
PubMed1995

Efficacy of slow-releasing anticancer drug delivery systems on transplantable osteosarcomas in rats.

New drug delivery systems for cis-diamminedichloroplatinum (CDDP) incorporated into vehicles, such as polymethylmethacrylate (PMMA), fibrin glue (F.G.), alpha-tricalciumphosphate (TCP) and ethylenevinyleacetate copolymer (Polymer) were examined using a rat osteosarcoma model. The materials containing CDDP were directly implanted into the tumors or subcutaneous tissue of rats, and the inhibitory effects on tumor growth and lung metastasis were evaluated. Data on in vitro kinetics of CDDP release revealed good results for both TCP and F.G., and the release pattern from TCP to be most appropriate for a slow-releasing drug delivery system. This was supported by the results of the implantation experiments, whereby the direct implantation of TCP containing CDDP (CDDP-TCP) into tumors, gave significantly better inhibitions of tumor growth and metastasis than either non-treatment (P < 0.01) or subcutaneous implantation (P < 0.05). In a second experiment, using different administration procedures, different inhibitory effects on tumor growth and lung metastatic potency were observed with intra-arterial and intravenous CDDP administration, as well as with CDDP-TCP implanted subcutaneously. Suppression effects of CDDP (10 mg/kg)-TCP directly implanted into tumors were equal to those of intra-arterial (2.5 mg/kg) and intravenous (5.0 mg/kg) administrations. The present results suggest CDDP-TCP implantation to be effective as a slow-release drug delivery system for inhibiting tumor growth and metastasis, and that it should be a useful adjuvant to conventional i.v. or i.a. chemotherapy.

Animals↗
PubMed1993

Preparation and characterization of porous apatite ceramics coated with beta-tricalcium phosphate.

Hydroxyapatite (Ca10(PO4)6(OH)2; HA) is one of the most biocompatible materials with bones, and porous HA is promising bone substitute materials for clinical applications. While there are reports that beta-tricalcium phosphate (Ca3(PO4)2; TCP) has higher resorbability than HA when the material is implanted in a bone defect. In the present study, porous HA coated with beta-TCP was prepared by our unique method. The porous HA of about 60% porosity with interconnecting pore structure was soaked in diammonium hydrogen phosphate solution, and then the HA was sintered at 900 degrees C for 3 h. beta-TCP was revealed by X-ray diffractometry on the surface of porous HA. It was possible to control the content of surface-formed beta-TCP arbitrary by varying the concentration of the solution. The obtained HA coated with 33 wt% beta-TCP (33TCP) had about 60% open porosity with the pore size from 150 to 400 microns. The average compressive strength of this porous ceramics was 17.5 MPa. Surface coated HA with beta-TCP deprived of the brittleness in handling. The weight of HA implanted into muscles was increased obviously at 4 weeks because of formation of carbonate hydroxyapatite on the surface of HA. The weight of 33TCP was scarcely changed up to 12 weeks, but the weight tended to increase at 24 weeks. The carbonate hydroxyapatite was not formed on 33TCP at 4 weeks, but formed on it at 24 weeks. Therefore beta-TCP coated porous HA behaved like beta-TCP initially after implantation, and then behaved like HA.

Animals↗
PubMed2000

Involvement of T-complex protein-1delta in dopamine triggered apoptosis in chick embryo sympathetic neurons.

The neurotransmitter dopamine (DA) is capable of inducing apoptosis in post-mitotic sympathetic neurons via its oxidative metabolites. The differential display method was applied to cultured sympathetic neurons in an effort to detect genes whose expression is transcriptionally regulated during the early stages of DA-triggered apoptosis. One of the up-regulated genes was identified as the chick homologue to T-complex polypeptide-1delta (TCP-1delta), a member of the molecular chaperone family of proteins. Each chaperone protein is a complex of seven to nine different subunits. A full-length clone of 1.9 kilobases was isolated containing an open reading frame of 536 amino acids with a predicted molecular weight of 57,736. Comparison with the mouse TCP-1delta revealed 78 and 91% homology on the DNA and protein levels, respectively. Northern blot analysis disclosed a steady and significant increase in mRNA levels of TCP-1delta after DA administration, reaching a peak between 4 and 9 h and declining thereafter. Induction of the TCP-1delta protein levels was also observed as a function of DA treatment. Overexpression of TCP-1delta in sympathetic neurons accelerated DA-induced apoptosis; inhibition of TCP-1delta expression in these neurons using antisense technology significantly reduced DA-induced neuronal death. These findings suggest a functional role for TCP-1delta as a positive mediator of DA-induced neuronal apoptosis.

Amino Acid Sequence↗
PubMed1997

The effects of calcium phosphate particles on the growth of osteoblasts.

With advances in ceramics technology, calcium phosphate bioceramics have been applied as bone substitutes for several decades. The focus of this work is to elucidate the biocompatibility of the particulates of various calcium phosphate cytotoxicities. Four different kinds of calcium phosphate powders, including beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA), beta-dicalcium pyrophosphate (beta-DCP), and sintered beta-dicalcium pyrophosphate (SDCP), were tested by osteoblast cell culture. The results were analyzed by cell count, concentration of transforming growth factor-beta 1 (TGF-beta 1), alkaline phosphatase (ALP), and prostaglandin E2 (PGE2) in culture media. The changes were most significant when osteoblasts were cultured with beta-TCP and HA bioceramics. The changes in cell population of the beta-TCP and HA were quite low in the first 3 days, then increased gradually toward the seventh day. The changes in TGF-beta 1 concentration in culture medium inversely related to the changes in cell population. The ALP titer in the culture media of the beta-TCP and HA were quite high in the first 3 days, then decreased rapidly between the third and seventh days. The concentrations of PGE2 in the culture media tested were quite high on the first day, decreased rapidly to the third day, and then gradually until the seventh day. The changes in the beta-DCP and SDCP were quite similar to those of HA and beta-TCP but much less significant. We conclude that HA and beta-TCP have an inhibitory effect on the growth of osteoblasts. The inhibitins effects of the HA and beta-TCP powders on the osteoblast cell cultures possibly are mediated by the increased synthesis of PGE2.

Alkaline Phosphatase↗
PubMed2002

Implanted octacalcium phosphate is more resorbable than beta-tricalcium phosphate and hydroxyapatite.

Our previous studies have suggested that synthetic octacalcium phosphate (OCP) could be resorbed and replaced by newly formed bone if implanted in rat skull defects. We hypothesized that the implanted OCP is more resorbable than other commonly used bone graft substitutes of calcium phosphate compounds, such as hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP). To test the hypothesis, the present study was designed to compare histomorphometrically resorption of the implanted OCP, HA, and beta-TCP, which were kept in the experimental cranial defect of rats for a long term. A full thickness of standardized trephine defect was made in the rat parietal bone, and the same volume of granules of OCP, HA, and beta-TCP were implanted into the defect. Five specimens of each group were fixed 6 months after implantation. The percentage of remaining implants (r-Imp%) and newly formed bone (n-Bone%) in the defect was analyzed histomorphometrically. The statistical analysis showed that the r-Imp% of OCP was significantly lower than that of HA and beta-TCP. In contrast, the n-Bone% of OCP was significantly higher than that of HA and beta-TCP. The present study has shown that the implanted OCP in the rat cranial defect is more resorbable than the implanted beta-TCP and HA, whereas the implanted OCP enhances bone formation more than the implanted beta-TCP and HA.

Animals↗
PubMed1991

Bone bonding mechanism of beta-tricalcium phosphate.

It has been proposed that the formation of a surface apatite layer in vivo on surface active ceramics is an essential condition for chemical bonding between ceramics and bone tissue. To clarify the difference in bone-bonding mechanisms between surface active ceramics and bioresorbable ceramics, two experiments were performed using plates of dense beta-tricalcium phosphate (beta-TCP). First, plates of beta-TCP were implanted subcutaneously in rats for 8 weeks. Surface change due to bioresorption was observed with scanning electron microscopy. Formation of the apatite layer on the surface was investigated using thin-film x-ray diffraction and Fourier transform infrared reflection spectroscopy. Second, plates of beta-TCP were implanted in tibiae of rabbits for 8 and 25 weeks and subjected to the detaching test to measure bone-bonding strength. beta-TCP bonded strongly to bone. Undecalcified sections of the interface of bone and beta-TCP were examined with SEM-EPMA. However, by physicochemical methods, no formation of surface apatite layer was observed. These results suggest that beta-TCP bonds to bone through microanchoring between bone and rough surface of resorbed beta-TCP.

Animals↗
PubMed1992

Role of serum vitronectin and fibronectin in adhesion of fibroblasts following seeding onto tissue culture polystyrene.

The suitability of polymeric biomaterials as surfaces for the attachment and growth of cells has often been investigated in tissue culture. In this study the contribution that adsorption of serum fibronectin (Fn) or vitronectin (Vn) make to the attachment and spreading of fibroblast cells during the first 90 min following seeding was determined for two modified tissue culture polystyrenes, as model biomaterial surfaces. The amount of serum Vn and Fn which adsorbed onto tissue culture grade polystyrene (TCP) from different serum concentrations over the range of 0.1-30% (v/v) were determined and compared to attachment of cells of the BHK-21 and HT1080 fibroblast lines. There was no simple correlation between the amount of Fn or the amount of Vn adsorbed and cell attachment and spreading. The requirement for Fn or Vn for attachment and spreading of BHK-21 or HT1080 cells onto modified polystyrene (either TCP or to Primaria) during the first 90 min of cell culture was directly tested by selective removal of Fn or Vn from the serum prior to addition to the culture medium. Attachment and spreading of BHK-21 or HT1080 cells onto TCP or Primaria surfaces were reduced in a concentration-dependent manner when the cells were seeded in medium containing 2% (v/v) or higher concentrations of Vn-depleted serum. BHK-21 cells or HT1080 cells seeded in medium containing Fn-depleted serum (which contained Vn) attached and spread onto TCP or Primaria. Both BHK-21 cells and HT1080 cells failed to attach to TCP or Primaria when seeded in medium containing serum depleted of both Vn and Fn. The requirement for serum Vn or Fn for fibroblast attachment to TCP was also tested using cells of a human dermal fibroblast strain. The attachment of the dermal fibroblasts to TCP during the first 90 min of culture was not decreased by depletion of Vn from the 15% (v/v) serum, but there was a reduction in the proportion of the attached cells which had spread. Selective depletion of serum Fn did not have any effect on either cell attachment or spreading. Our results show that for fibroblast cells, particularly with cell lines such as BHK-21 or HT1080 but also with cell strains, the first binding of cells onto tissue culture polystyrene when plated in medium containing serum is a result of adsorption onto the surface of serum Vn. The adsorption of serum Vn onto the surface overcomes the effect of serum components which tend to decrease cell attachment.

Adsorption↗
PubMed2003

Stimulation of bone formation with an in situ setting tricalcium phosphate/rhBMP-2 composite in rats.

The aim of the study was to determine bone-regenerative effects of an in situ setting tricalcium phosphate (TCP) cement combined with rhBMP-2 and to compare it with autologous bone graft. A trepanation defect of 1.5 mm in the femur diaphysis of Sprague-Dawley rats was filled with an in situ setting TCP cement combined with 0, 0.25, 2.5, or 25 microg of rhBMP-2, an autologous bone graft, or left empty. The rats were euthanized after 1 and 3 weeks and examined by radiography, histology, histomorphometry, and bending tests. All TCP groups with or without BMP-2 showed a good bony ingrowth with a close bone-cement contact. Histomorphometric analysis showed no increase of new bone formation in the defect, but a dose-dependent increase in callus formation with a maximum at 25 microg of rhBMP-2. As shown with intravital fluorochrome staining, new bone formation started earlier using rhBMP-2. Bone strength, measured in a three-point bending test and expressed in percentage of the contralateral healthy femur, was 75% for TCP + 25 microg rhBMP-2, 44% for TCP + 2.5 microg rhBMP-2, and 34% for autologous bone graft. TCP particles were detectable in all groups after 3 weeks. Callus formation and bending strength of the TCP + 25 microg rhBMP-2 group was superior to autologous bone graft. So TCP/rhBMP-2 composites may prove to be an effective substitute for autologous bone grafts.

Animals↗