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Embryonic and postnatal development of N-(1-[2-thienyl]cyclohexyl)[3H]piperidine binding sites in rat forebrain homogenates and slices.

The development of N-(1-[2-thienyl]-cyclohexyl)[3H]piperidine [( 3H]TCP) binding to phencyclidine (PCP) receptors in both brain homogenates and slices has been investigated in the rat. The specific binding sites for [3H]TCP in the homogenate were already detected at prenatal stages and steadily increased after birth. A similar developmental pattern was seen in the autoradiography of the [3H]TCP binding to the brain slice in which the distribution of the binding in the young is more homogeneous than that in adult. There was an increase in the Bmax without changes in the Kd of the [3H]TCP binding and there was no change in inhibition of the binding by TCP, PCP and D-(-)-2-amino-5-phosphonovalerate during postnatal maturation. These findings suggest an increase in the density with no change in the affinity of PCP receptors and the absence of a change in the interaction between the PCP and N-methyl-D-aspartate receptors in the developing rat forebrain.

Aging↗

Synthesis and evaluation of 1-(1-[5-(2'-[18F]fluoroethyl)-2-thienyl]-cyclohexyl)piperidine as a potential in vivo radioligand for the NMDA receptor-channel complex.

1-(1-[5-(2'-[18F]Fluoroethyl)-2-thienyl]cyclohexyl)piperidine (18FE-TCP) was prepared as a fluorine-substituted analogue of the potent NMDA receptor channel blocker, 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), by the mesylate displacement with [18F]fluoride ion with isolated radiochemical yields of 6-12%, and the synthesis time including a two step HPLC purification was 120 min. The regional distribution in rat brain after i.v. injection of 18FE-TCP was heterogeneous and similar to the known distribution of phencyclidine recognition sites, with hippocampus-cerebellum, striatum-cerebellum and cerebral cortex-cerebellum concentration ratios of 2.08, 1.7 and 1.54, respectively, 15 min post-injection. Furthermore, this localized regional cerebral distribution was blocked by co-injection with the unlabelled FE-TCP or pretreatment with cis-2-hydroxymethyl-r-1-(N-piperidyl)-1-(2-thienyl)cyclohexane, with the greatest reductions seen in the hippocampus followed by the striatum and cerebral cortex. However, relatively low receptor binding affinity and high non-specific binding due to its high lipophilicity suggest that 18FE-TCP may not be a suitable radioligand for in vivo PET investigations of the NMDA receptor-channel complex.

Animals↗

Sintering and robocasting of beta-tricalcium phosphate scaffolds for orthopaedic applications.

beta-Tricalcium phosphate (beta-TCP) scaffolds with designed, three-dimensional (3-D) geometry and mesoscale porosity have been fabricated by direct-write assembly (robocasting) techniques. Concentrated beta-TCP inks with suitable viscoelastic properties were developed to enable the fabrication of the complex 3-D structures. A comprehensive study of the sintering behavior of TCP as a function of the calcium content in the starting powder was also carried out, and the optimal heat treatment for fabricating scaffolds with dense beta-TCP rods has been determined. Such analysis provides clues to controlling the microstructure of the fabricated structures and, therefore, enabling the fabrication by robocasting of TCP scaffolds with tailored performance for bone tissue engineering applications.

Biocompatible Materials↗

The inflammatory responses to silk films in vitro and in vivo.

Silks have a long history of biomedical use as sutures. Silk can be purified, chemically modified to attach RGD sequences and processed into highly porous scaffolds for tissue engineering. We report biocompatibility studies of silk films (with or without covalently bound RGD) that were seeded with bone-marrow derived mesenchymal stem cells (MSC) and (a) cultured in vitro with human MSC or (b) seeded with autologous rat MSC and implanted in vivo. Controls for in vitro studies included tissue culture plastic (TCP; negative control), TCP with lipopolysaccharide (LPS) in the cell culture medium (positive control), and collagen films; controls for in vivo studies included collagen, PLA and TCP. After 9 h of culture, the expression of the pro-inflammatory Interleukin 1 beta (IL-1beta) and inflammatory cyclooxygenase 2 (COX-2) in human MSC were comparable for silk, collagen and TCP. After 30 and 96 h, gene expression of IL-1beta and COX-2 in MSC returned to the baseline (pre-seeding) levels. These data were corroborated by measuring IL-1beta and prostaglandin E2 levels in culture medium. The rate of cell proliferation was higher on silk films than either on collagen or TCP. In vivo, films made of silk, collagen or PLA were seeded with rat MSCs, implanted intramuscularly in rats and harvested after 6 weeks. Histological and immunohistochemical evaluation of silk explants revealed the presence of circumferentially oriented fibroblasts, few blood vessels, macrophages at the implant-host interface, and the absence of giant cells. Inflammatory tissue reaction was more conspicuous around collagen films and even more around PLA films when compared to silk. These data suggest that (a) purified degradable silk is biocompatible and (b) the in vitro cell culture model (hMSC seeded and cultured on biomaterial films) gave inflammatory responses that were comparable to those observed in vivo.

Animals↗

Correlating crystallinity and reactivity in an alpha-tricalcium phosphate.

In this study, the effect of how variant milling time affects material characteristics of alpha phase tricalcium phosphate powder (alpha-TCP) was studied. Two alpha-TCP batches were separated in small lots and milled for various times for up to 4 h. The resulting milled lots were characterized by measuring their crystallinity, particle size, specific surface area, thermal stability, and heat released during hydration. Mechanical treatment was seen to greatly increase the alpha-TCP X-ray amorphous fraction and heat release during hydration, almost independently of alpha-TCP particle size and specific surface area. Therefore, the results suggest that the formation and presence of an X-ray amorphous phase in the alpha-TCP powder greatly contribute to its reactivity. The exotherm of the powders increases from 103 to 238 kJ/mol after milling.

Biocompatible Materials↗

Synthesis and characterization of single-phase silicon-substituted alpha-tricalcium phosphate.

Silicon-substituted calcium phosphate (CaP) powders with a Ca/(P+Si) ratio of 1.50 have been prepared by a wet chemical method, with silicon contents up to 2.16 weight percent (wt%). Sintering for 2 h at 1250 degrees C yields single-phase silicon-substituted alpha tricalcium phosphate (Si-alpha-TCP) for compositions between 0.59 and 1.14 wt% silicon. The sintered powders have been characterized with X-ray fluorescence (XRF) spectrometry, X-ray diffraction (XRD), attenuated total reflection infrared spectroscopy (ATR-IR) and transmission electron microscopy (TEM). Compositions with less than 0.59 wt% silicon result in mixtures of Si-alpha-TCP, beta-TCP, and calcium hydroxyapatite (HA), while compositions with more than 1.14 wt% silicon result in mixtures of Si-alpha-TCP and HA. The lattice parameters of single-phase Si-alpha-TCP prepared with 0.87 wt% silicon are a=12.874(1)A, b = 27.372(2) A, c = 15.225(1) A, and beta = 126.38(1) degrees .

Bone Substitutes↗

Dacthal and chlorophenoxy herbicides and chlorothalonil fungicide in eggs of osprey (Pandion haliaetus) from the Duwamish-Lake Washington-Puget Sound area of Washington state, USA.

Current-use chlorophenoxy herbicides including 2,4-dichlorophenoxyacetic acid, dicamba, triclopyr, dicamba, dimethyl tetrachloroterephthalate (DCPA or dacthal), and the metabolite of pyrethroids, 3-phenoxybenzoic acid (3-PBA), and the fungicide, chlorothalonil, were investigated in the eggs of osprey (Pandion haliaetus) that were collected from 15 sites from five study areas Puget Sound/Seattle area of Washington State, USA. DCPA differs from acidic chlorophenoxy herbicides, and is not readily hydrolyzed to free acid or acid metabolites, and thus we developed a new method. Of the 12 chlorophenoxy herbicides and chlorothalonil analyzed only DCPA could be quantified at six of these sites (2.0 to 10.3 pg/g fresh weight). However, higher levels (6.9 to 85.5 pg/g fresh weight) of the unexpected DCPA structural isomer, dimethyl tetrachlorophthalate (diMe-TCP) were quantified in eggs from all sites. diMe-TCP concentrations tended to be higher in eggs from the Everett Harbor area. As diMe-TCP is not an industrial product, and not commercially available, the source of diMe-TCP is unclear. Regardless, these findings indicate that DCPA and diMe-TCP can be accumulated in the food chain of fish-eating osprey, and transferred in ovo to eggs, and thus may be of concern to the health of the developing chick and the general reproductive health of this osprey population.

2,4-Dichlorophenoxyacetic Acid↗

Synthetic, pure-phase beta-tricalcium phosphate ceramic granules (Cerasorb) for bone regeneration in the reconstructive surgery of the jaws.

The aim of this study was to investigate the long-term effect of the ceramic beta-tricalcium phosphate (beta-TCP) at different sites of alveolar reconstruction and to evaluate its properties. From 1997 to 2002, beta-TCP was implanted as bone substitute in 152 patients using a standardized study protocol. Main indications were the filling of large mandibular cysts (n=52), secondary and tertiary alveolar cleft grafting (n=38), periodontal defects (n=24) and maxillary sinus floor augmentation (n=16). For defects exceeding 2cm in diameter, beta-TCP was combined with autologous bone taken from the retromolar area, the maxillary tuberosity or the chin region. A radiological, clinical and ultrasonographical examination was carried out 4, 12 and 52 weeks postoperative. In 16 cases, biopsies were taken after 12 months indicating complete bony regeneration. While wound-healing disturbances occurred in 9.2% of cases, partial loss of the bone substitute material was found in 5.9%, while total loss occurred in only 2%. Complete radiological replacement of beta-TCP by autologous bone was found after approximately 12 months, indicating its osteoconductive properties. Because of its versatility, low complication rate and good long-term results, synthetic, pure-phase beta-TCP is a suitable material for the filling of bone defects in the alveolar region.

Adolescent↗

Preparation of prefabricated vascularized bone graft with neoangiogenesis by combination of autologous tissue and biodegradable materials.

Prefabricated vascularized bone grafts have previously been prepared by combining an autologous vessel bundle with auto-particulate cancellous bone and marrow (PCBM) and a biodegradable membrane. Only small quantities of low-density vascularized bone tissue have been formed using this method. The authors of the present study combined beta-tricalcium phosphate (beta-TCP), a biodegradable ceramic, with a prefabricated vascularized bone graft to augment osteogenesis. A saphenous vessel bundle from a rat was wrapped in a biodegradable membrane. Then, autologous PCBM was mixed with beta-TCP granules and packed into the rolled membrane. In the control group, beta-TCP was omitted. Bone formation was histologically assessed 6 and 9 weeks after implantation. The volume of newly formed bone tissue in the rolled membrane was greater in the presence of beta-TCP granules than in the control. Microvessels had formed throughout the new bone tissue. When a prefabricated vascularized bone graft was onlay-grafted to the femur of the same rat, the prefabricated vascularized bone graft directly fused to the cortical surface of the femur, with no intervening fibrous tissue. These findings suggest that beta-TCP in combination with PCBM enhances the volume and density of bone tissue in prefabricated vascularized bone grafts.

Absorbable Implants↗

Assessment of i-125 prostate implants by tumor bioeffect.

PURPOSE: A method of prostate implant dose distribution assessment using a bioeffect model that incorporates a distribution of tumor cell densities is demonstrated. This method provides both a quantitative method of describing implant quality and spatial information related to the location of underdosed regions of the prostate. This model, unlike any other, takes into account the likelihood of finding cancer cells in the underdosed region. METHODS AND MATERIAL: The prostate volumes of 5 patients were divided into multiple subsections and a unique cell density was assigned to each subsection. The assigned cell density was a function of probability of finding tumor foci in that subsection. The tumor control probability (TCP) for each subsection was then calculated to identify the location of any significantly underdosed part of the prostate. In addition, a single TCP value for the entire prostate was calculated to score the overall quality of the implant. RESULTS: Adequately dosed subsections scored TCP values greater than 0.80. The TCP for underdosed regions fell dramatically particularly in subsections at higher risk of containing tumor cells. CONCLUSIONS: Despite uncertainties in radiobiological parameters used to calculate the TCP and the distribution of cancer foci through the prostate, the bioeffect model was found to be useful in identifying regions of underdosed prostate that may be at risk of local recurrence due to inadequate dose. Unlike the isodose distribution, the model has the potential to demonstrate that small volumes of tissue underdosed in regions most likely to contain higher numbers of tumor cells may be more significant than larger volumes irradiated to a lower dose but with a lower probability of containing cancer cells.

Brachytherapy↗

Impact of tumor repopulation on radiotherapy planning.

PURPOSE: Biologic/functional imaging (e.g., fluorodeoxyglucose/3'-deoxy-3'-fluorothymidine-positron emission tomography) is promising to provide information on tumor cell repopulation. Such information is important in the design of biologically conformal radiotherapy for cancer. The questions remaining unclear are whether it is necessary to escalate the dose to the regions with rapid cell repopulation in the tumor target and, if so, by how much. The purpose of this work was to address these questions using radiobiologic modeling. METHODS AND MATERIALS: The generalized linear-quadratic model, extended to account for the effect of clonogenic cell repopulation, was used to calculate the cell-killing efficiency of radiotherapy. The standard Poisson tumor control probability (TCP) model was used to bridge cell killing to treatment outcome. Prostate cancer was chosen as the example for this study. In situ measurements of prostate cancer patients have shown that the potential doubling time of tumor cells has a large variation, ranging from 15 to 170 days. On the basis of the linear-quadratic and TCP parameters (alpha = 0.14 Gy(-1), alpha/beta = 3.1 Gy, and the number of clonogens K = 10(6)-10(7) cells) determined in earlier studies, we evaluated the influence of tumor cell repopulation during protracted treatment courses on treatment outcome. The dose escalations, which can be used to combat aggressive cell repopulation in regions with different doubling times (15-170 days) and sizes (5, 10, 15, and 40 cm(3) of a 40-cm(3) tumor), were calculated for commonly practiced radiotherapy modalities. The influence of linear-quadratic parameters on this calculation was also considered. RESULTS: The impact of tumor cell repopulation on TCP and the corresponding dose escalation required to account for this impact were investigated for both external beam radiotherapy and permanent implantation. The results indicated that for regions with aggressive tumor cell growth, dose escalation is necessary to compensate for the repopulation effect. For example, for tumors with an effective doubling time changing from 42 days to 15 days, the prescription dose of external beam radiotherapy needs to be increased from 75.6 to 81 Gy to maintain a target TCP of 80% for intermediate-risk prostate cancer. For (125)I implants, dose escalation from 152 to 160 Gy is required for the same target TCP. These data were calculated on the basis of an alpha/beta ratio of 3.1 Gy. Greater dose escalations are required if the alpha/beta ratio is 1.5 Gy (e.g., 88 Gy for external beam radiotherapy or 180 Gy for (125)I implantation for the same treatment outcome). Our study results showed that it is important to cover the entire tumor volume, including all aggressive spots, with the desired prescription dose, especially for low-dose-rate brachytherapy. CONCLUSION: Dose escalation is necessary to offset the accelerated tumor cell repopulation during prolonged treatment courses. This study provides a preliminary estimate of the dose escalation for prostate cancer based on the in situ measurements of potential doubling time and radiobiologic models. The proposed dose prescriptions are technically feasible for clinical trials.

Brachytherapy↗

Dosimetric effect of respiratory motion in external beam radiotherapy of the lung.

BACKGROUND AND PURPOSE: To study the effect of breathing motion on gross tumor volume (GTV) coverage for lung tumors using dose-volume histograms and relevant dosimetric indices. PATIENTS AND METHODS: Treatment plans were chosen for 12 patients treated at our institution for lung carcinoma. GTV volumes of these patients ranged from 1.2 to 97.3 cm(3). A margin of 1-2 cm was used to generate the planning target volume (PTV). Additional margins of 0.6-1.0 cm were added to the PTV when designing treatment portals. For the purposes of TCP calculation, the prescription dose was assumed to be 70 Gy to remove the effects of prescription differences. Setup error was incorporated into the evaluation of treatment plans with a systematic component of sigma(RL) = 0.2 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.3 cm and a random component of sigma(RL) = 0.3 cm, sigma(AP) = 0.3 cm, and sigma(SI) = 0.3 cm. Breathing motion was incorporated into these plans based on an independent analysis of fluoroscopic movies of the diaphragm for 7 patients. The systematic component of breathing motion (sigma(RL) = 0.3 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.6 cm) was incorporated into the treatment plans on a slice by slice basis. The intrafractional component of breathing motion (sigma(RL) = 0.3 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.6 cm) was incorporated by averaging the dose calculation over all displacements of the breathing cycle. Each patient was simulated 500 times to discern the range of possible outcomes. The simulations were repeated for a worst case scenario which used only breathing data with a large diaphragmatic excursion, both with and without intrafractional breathing motion. RESULTS: Dose to 95% of the GTV (D95), volume of the GTV receiving 95% of the prescription dose (V95) and TCP changed an average of -1.4+/-4.2, -1.0+/-3.3, and -1.4+/-3.8%, respectively, with the incorporation of normal breathing effects. In the worst case scenario (heavy breathers), D95 and V95 changed an average of -9.8+/-10.1 and -8.3+/-11.3%, respectively, and TCP changed by -8.1+/-9.1%. GTVs with volumes greater than 60 cm(3) showed stronger sensitivity to breathing especially if the shape was non-ellipsoidal. In the normal breathing case, the probability of a decrease in D95, V95, or TCP of a magnitude greater than 10% is less than 4%, and in the worse case scenario this probability is approximately 30-40% with intrafractional breathing motion included, and less than 10% with intrafractional breathing motion not included. CONCLUSIONS: With the PTV margins routinely used at our center, the effects of normal breathing on coverage are small on the average, with a less than 4% chance of a 10% or greater decrease in D95, V95, or TCP. However, in patients with large respiration-induced motion, the effect can be significant and efforts to identify such patients are important.

Artifacts↗

Prehospital transcutaneous cardiac pacing for symptomatic bradycardia or bradyasystolic cardiac arrest: a systematic review.

BACKGROUND: Advanced cardiac life support (ACLS) guidelines suggest transcutaneous cardiac pacing (TCP) for the treatment of symptomatic bradycardia (SB) and bradyasystolic cardiac arrest (BACA). Many EMS systems are extrapolating these guidelines and employing TCP in the prehospital setting. Our objective was to conduct a systematic review to determine the efficacy of prehospital TCP in the management of these two conditions. METHODS: MEDLINE (1966-2004), EMBase and Science Citation Index (1980-2004) were searched using: prehospital/emergency medical services; external/transcutaneous; pacing. Two reviewer teams blinded to the source and author conducted a hierarchical selection (title, abstract, article) and quality assessment using a validated scale. Kappa agreement at each level of review was measured. Data abstraction was done by consensus. RESULTS: Thirty-four articles were identified and seven selected (Kappa agreement; title: 0.85, abstract: 0.78, full article: 0.82). Article quality was poor in all trials. There were three case series (BACA, n=215), three unblinded randomised controlled trials (one BACA, two BACA+SB), and one subgroup (SB) analysis. In the case series of paced BACA patients, 0/215 survived to hospital discharge. In the BACA trials 16/509 (paced) versus14/497 (control) survived to discharge. In a subgroup of one SB trial 5/6 (paced) versus 1/7 (control) survived to discharge (p=0.01). When a SB trial subgroup was combined with a case series 4/27 (paced) versus 0/24 (control) survived to discharge (p=0.07). CONCLUSIONS: In the prehospital setting, there is no evidence to support the use of TCP in bradyasystolic cardiac arrest. There is inadequate evidence to determine the efficacy of prehospital TCP in the treatment of symptomatic bradycardia.

Bradycardia↗

Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel.

Previous studies have established the presence of overlapping binding sites for the noncompetitive antagonists (NCAs) amobarbital, tetracaine, and 3-trifluoromethyl-3-(m-[(125)I]iodophenyl) diazirine ([(125)I]TID) within the ion channel of the Torpedo nicotinic acetylcholine receptor (AChR) in the resting state. These well-characterized NCAs and competitive radioligand binding and photolabeling experiments were employed to better characterize the interaction of the dissociative anesthetics ketamine and thienylcycloexylpiperidine (TCP) with the resting AChR. Our experiments yielded what appear to be conflicting results: (i) both ketamine and TCP potentiated [(125)I]TID photoincorporation into AChR subunits; and (ii) ketamine and TCP had very little effect on [(14)C]amobarbital binding. Nevertheless, (iii) both ketamine and TCP completely displaced [(3)H]tetracaine binding (K(i)s approximately 20.9 and 2.0 microM, respectively) by a mutually exclusive mechanism. To reconcile these results we propose that, in the resting ion channel, TCP and ketamine bind to a site that is spatially distinct from the TID and barbiturate locus, while tetracaine bridges both binding sites.

Allosteric Site↗

Effects of stress and tranylcypromine on amphetamine-induced locomotor activity and GABA(B) receptor function in rat brain.

Modification in gamma-aminobutyric acid-B (GABA(B)) receptors may contribute to the symptoms of some neurological and psychiatric disorders and to the clinical response to psychotherapeutics. The present study was undertaken to determine whether chronic administration of tranylcypromine (TCP), an antidepressant, and chronic stress influence GABA(B) receptor function in rat brain. The results indicate that TCP treatment, but not stress, increases GABA(B) receptor activity in the cerebral cortex, as measured by baclofen-stimulated GTPgammaS binding. In addition, chronic administration of TCP enhances significantly the locomotor response to a single dose of amphetamine, an effect that is abolished by restraint stress. These results indicate that although TCP administration modifies brain GABA(B) receptor activity, which may contribute to the antidepressant response to this agent, this effect is unrelated to the interaction of stress and TCP treatment on the locomotor response to amphetamine.

Amphetamine↗

Binding of [3H]2-(2-benzofuranyl)-2-imidazoline (BFI) to human brain: potentiation by tranylcypromine.

Recently, a new imidazoline (I2) ligand, [3H]2-(2-benzofuranyl)-2-imidazoline (BFI) was shown to be more selective for I2 vs alpha 2 binding in rodent brain. We characterized [3H]BFI binding in human brain cortex and lateral reticular nucleus (NRL). Membranes were incubated with [3H]BFI at 22 degrees C in 50 mM Tris, 1.5 mM EDTA at pH 7.5. Saturation experiments with [3H]BFI (0.5-80 nM) were analyzed using non-linear curve fitting. The NRL had 4X more binding sites than cortex with similar affinity (Bmax = 2085 +/- 732 and 471 +/- 41 fmol/mg protein; KD = 9.3 +/- 3.5 and 11.9 +/- 2.7 nM, respectively). In competition studies, cortical [3H]BFI binding was displaced in order of decreasing potency by clorgyline > BFI > or = cirazoline > idazoxan > or = guanabenz > clonidine > RX821002. The monoamine oxidase (MAO) inhibitor tranylcypromine (TCP) (1 nM-10 microM), markedly enhanced [3H]BFI binding in both NRL and cortex. Enhanced binding was maximal at 300 nM (12 X control) and returned to baseline at 30 microM. Potentiation was not seen with pargyline or clorgyline. TCP did not effect [3H]BFI binding in rat cortex, or [3H]idazoxan binding in human cortex and NRL. In human cortex, inhibition of MAO by preincubation with pargyline (10 micro M) abolished the TCP effect. Upon preincubation with TCP, the stimulation of [3H]BFI binding was dose-dependently related to a simultaneous inhibition of MAO. Thus, [3H]BFI labels a site in human NRL and cortex that appears similar to the previously described I2 site labeled by [3H]idazoxan. However, [3H]BFI binding is dramatically stimulated by TCP in human brain via a mechanism dependent on endogenous MAO activity.

Animals↗

Effects of antibacterial capping agents on dental pulps of monkeys mechanically exposed to oral microflora.

The effects of antibacterial drugs on bacterially contaminated dental pulps were investigated in monkeys. Class V buccal cavities with pulpal exposures were prepared and then left open to the oral environment for 24 h. The exposed pulps were capped with alpha-tricalcium phosphate (alpha-TCP) containing a mixture of antibacterial drugs. Either alpha-TCP or Ca(OH)2 was used as a control. Pulpal responses were histologically evaluated after 4 wk. Those teeth capped with alpha-TCP alone showed total pulp necrosis and bacterial growth within the pulp chamber. By contrast, the pulps capped with alpha-TCP containing mixed antibacterial drugs remained almost normal without any necrotic layer, but showed persistent absorbing response to capping materials and no signs of hard tissue barrier formation. In teeth capped with Ca(OH)2, a hard tissue barrier was formed below the exposure site, with a wide loss of pulp tissue. No inflammation was seen under the barrier. These results indicate that mixed antibacterial drugs added to alpha-TCP effectively disinfected pulpal lesions, without destroying any of the sound pulp tissue. However, hard tissue barrier formation was delayed by this mixture as compared with Ca(OH)2.

Animals↗

Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate.

New injectable, in situ crosslinkable biodegradable polymer composites were investigated consisting of poly(propylene fumarate) (PPF), poly(ethylene glycol)-dimethacrylate (PEG-DMA), and beta-tricalcium phosphate (beta-TCP). We examined the effects of the PEG-DMA/PPF double-bond ratio and beta-TCP content on the crosslinking characteristics of the composites including the maximum crosslinking temperature and the gel point, as well as the properties of the crosslinked composites such as the compressive strength and modulus, and the water-holding capacity. The maximum crosslinking temperature was constant averaging 39.7 degrees C for the composite formulations tested. The gel points varied from 8.0 +/- 1.0 to 12.6 +/- 2.5 min and were not affected by the relative amounts of PEG-DMA. The compressive strength at yield of PEG-DMA/PPF composites without beta-TCP increased from 5.9 +/- 1.0 to 11.2 +/- 2.2 MPa as the double-bond ratio of PEG-DMA/PPF increased from 0.38 to 1.88. An increase in compressive modulus was also observed from 30.2 +/- 3.5 to 58.4 +/- 6.2 MPa for the same range of the PEG-DMA/PPF double-bond ratio. Also, the addition of beta-TCP (33 wt%) enhanced the mechanical properties of all composites. The equilibrium water content of networks without beta-TCP increased from 21.7 +/- 0.2 to 30.6 +/- 0.2% for a double-bond ratio of PEG-DMA/PPF ranging from 0.38 to 1.88. However, the mechanical properties of the swollen composites under compression were smaller than the dry ones. These data demonstrate the feasibility of fabricating injectable biodegradable polymer composites with engineered mechanical properties for orthopedic tissue engineering.

Acrylates↗