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Effects of polyglactin mesh combined with resorbable calcium carbonate or replamineform hydroxyapatite on periodontal repair in dogs.

This study evaluates periodontal repair and biomaterial reaction following implantation of a polyglactin mesh with or without porous resorbable calcium carbonate (RCC) or porous replamineform hydroxyapatite (RHA) in conjunction with reconstructive surgery. Ligature- and surgically-induced interproximal periodontal defects of left and right mandibular premolar teeth in 7 dogs were used. Bilaterally, mesial defects of the 2nd, 3rd and 4th premolar teeth were treated with polyglactin mesh, polyglactin mesh and RHA, or polyglactin mesh and RCC, respectively. The polyglactin mesh, shaped according to the contour of the defect, was adapted to the experimental teeth; its coronal margin positioned immediately apical to the cemento-enamel junction. Gingival flap margins were adapted and sutured to cover the polyglactin mesh completely. Clinical healing was generally uneventful. The dogs were sacrificed to provide block sections for histologic evaluation at 1, 3, 6, 12, 26, 32 and 56 weeks following wound closure. Generally, cementum regeneration was observed beginning at week 6 in all groups. Bone regeneration was observed from week 3 in polyglactin mesh-treated groups, and from week 6 in polyglactin mesh+RCC or polyglactin mesh+RHA treated groups. Bone regeneration appeared enhanced in polyglactin mesh+RCC or polyglactin mesh+RHA treated defects at week 12 and 26, with little difference between the three experimental conditions at week 56. Polyglactin mesh degradation was observed at week 3 and appeared complete at week 12. The RHA did not appear to resorb, while the RCC was gradually replaced by bone from week 3. Within limitations of the study conditions, periodontal regeneration was observed following implantation of a polyglactin mesh with or without RCC or RHA in conjunction with reconstructive surgery. As a conclusion, there seems to be no significant difference in periodontal regeneration after 12 months of healing between the group treated with the membrane only, and the group treated with the membrane and the bone substitution material. Changes in connective fiber orientation over the 1st 12 weeks of healing may suggest that "fibrous encapsulation" observed in earlier studies may only represent a transient stage in periodontal regeneration.

Animals↗

The controlled resorption of porous alpha-tricalcium phosphate using a hydroxypropylcellulose coating.

Tricalcium phosphate (TCP) ceramic is known in orthopedics to be a bioresorbable bone substitute. A porous TCP ceramic body also has high potential as a drug delivery system in bony defects. Porous alpha-TCP ceramic can be easily fabricated using conventional sintering of beta-TCP, since alpha-TCP is the thermodynamically stable phase at temperatures above 1 100 degrees C. However, the solubility of alpha-TCP is much higher than that of beta-TCP. Therefore, the dissolution of porous alpha-TCP progresses at a higher rate than bone repair. In the present study, we attempted to reduce the dissolution rate of porous alpha-TCP by employing an organic polymer coating. We fabricated porous alpha-TCP ceramic with a continuous 10-50 microm diameter pore structure by sintering a body made from a beta-TCP and potato starch slurry. The porous body obtained was coated with hydroxypropylcellulose (HPC), and then subjected to heat treatment. The chemical durability and mechanical properties of the body were examined before and after coating with the HPC. The dissolution of porous alpha-TCP in buffered solutions was reduced by coating with HPC and drying at 60 degrees C. The compressive strength of the porous alpha-TCP was also improved by coating with HPC. The results of in vivo experiments showed that some parts of the porous alpha-TCP ceramic coated with HPC remained in the canal of the tibia of a rabbit four weeks after implantation, whereas no residual was observed in a non-coated alpha-TCP ceramic. Coating with HPC was found to be effective for controlling bioresorption and improving the workability of porous alpha-TCP ceramic. The prepared porous alpha-TCP ceramic is expected to be useful as a novel material for bone fillers by incorporating it with drugs or osteoinductive factors.

Animals↗

[Effect of calcitonin on regional blood flow in bones, serum levels of IGF-I and osteocalcin, density and weight of bone ash in oophorectomized rats].

It is known that in cases of increased bone remodelation rate, i.e. after castration, local bone blood flow is also increased. But in case of adequate hormonal substitution, bone blood flow, similarly as the remodelation rate, return to normal ranges. Until now, there is no knowledge, if other drug can influence enhanced bone blood flow in oophorectomized animals. In this study authors treated oophorectomized female rats with calcitonin and followed bone blood flow, together with biochemical parameters of bone remodelation activity (osteocalcine), IGF-I levels, weight of bone ash and bone density. The female rats were divided in four groups: controls, oophorectomized, with calcitonin and oophorectomized with calcitonin. The bone blood flow was determined by method of body dispersion of radioactive strontium labelled microspheres. The results of this study show, that, in comparison with controls, the bone remodelation rate (documented with increased osteocalcine levels) and radioactive strontium labelled microspheres capture in bone in increased after oophorectomy (p < 0.05). Ash weight and bone density were decreased (p < 0.05). Simultaneously, the blood IGF-I levels were increased (p < 0.05). After oophorectomized animals were treated with calcitonin, all parameters mentioned above headed towards normal ranges in comparison with group of oophorectomized female rats without calcitonin (p < 0.05). Changes of serum IGF-I levels follow changes of microspheres capture in each group of animals. Authors support the hypothesis, that blood levels of IGF-I could influence local bone blood flow. Calcitonin treatment of oophorectomized animals diminishes also decrement of ash weight and bone density. Results of this work show, that similarly as hormonal substitution therapy after oophorectomy, calcitonin also diminishes increased bone blood flow and bone remodelation parameters. The degree of bone blood flow is probably connected with activity of bone remodelling.

Animals↗

In vitro studies of human and rat osteoclast activity on hydroxyapatite, beta-tricalcium phosphate, calcium carbonate.

Investigations on the ceramic degradation caused by osteoclasts are designed to assess osteoclast-ceramic interactions and to determine which ceramics are more suitable for use as bone substitute. This study investigated the resorptive activity of osteoclasts on ceramics presenting different solubility rates. Osteoclasts isolated from new-born rat and from human giant cell tumour were cultured on different bioceramics: hydroxyapatite (HA), beta-tricalcium phosphate (TCP) and calcium carbonate (calcite). Cytoskeletal was revealed by actin labelling and ceramic surfaces were observed by scanning electron microscopy (SEM). On all materials, the distribution of actin in typical ring was revealed. SEM examinations showed a clear difference in the shape and the depth of resorption lacunae on different ceramics. On pure HA, a superficial attack, clearly visible but very little extended. Numerous resorption lacunae, deep and well-delimited were observed on pure beta-TCP, but attacks less punctually were detected too. On pure calcite, an attack with form of spikes, very widespread but superficial was revealed. Degradation measurements revealed a significant increase of P release from the phosphocalcic ceramics and of Ca from all ceramics in the presence of osteoclasts. The both cell models found these characteristics, the rat osteoclasts were also an excellent model to study the ceramic resorption.

Adsorption↗

[Experimental study of the effect of new bone formation on new type artificial bone composed of bioactive ceramics].

OBJECTIVE: To investigate the osteogenic potential of four kinds of new bioactive ceramics combined with bovine bone morphogenetic proteins (BMP) and to explore the feasibility of using compounds as bone substitute material. METHODS: Ninety-six rats were divided into 4 groups (24 in each group). BMP was combined with hydroxyapatite (HA), tricalcium phosphate (TCP), fluoridated-HA (FHA), and collagen-HA(CHA) respectively. The left thighs of the rats implanted with HA/BMP, TCP/BMP, FHA/BMP, and CHA/BMP were used as experimental groups. The right thighs of the rats implanted with HA, TCP, CHA, and decalcified dentin matrix (DDM) were used as control groups. The rats were sacrificed 1, 3, 5 and 7 weeks after implantation and bone induction was estimated by alkaline phosphatase (ALP), phosphorus (P), and total protein (TP) measurement. The histological observation and electronic microscope scanning of the implants were also made. RESULTS: The cartilage growth in the 4 experimental groups and the control group implanted with DDM was observed 1 week after operation and fibrous connective tissues were observed in the other 3 control groups. 3 weeks after implantation, lamellar bone with bone marrow and positive reaction in ALP stain were observed in the 4 experimental groups. No bone formation or positive reaction in ALP stain were observed in the control groups. The amount of ALP activity, P value, and new bone formation in the experimental groups were higher than those in the control group(P < 0.05). The amount of ALP activity, P value, and new bone formation in TCP/BMP group were higher than those in HA/BMP, CHA/BMP and FHA/BMP groups (P < 0.05). There was no significant difference in TP between the BMP treatment group and the control groups. From 5th to 7th week, new bone formation, histochemistry evaluation, and the level of ALP, P, TP value were as high as those in the 3rd week. CONCLUSION: New composite artificial bone of TCP/BMP, HA/BMP, CHA/BMP, and FHA/BMP all prove to be effective, but TCP/BMP is the most effective so that it is the most suitable biomaterial replacement of tissue.

Alkaline Phosphatase↗

Solubility of compositions in the system CaTi(x)Zr4-(x)(PO4)6 with x = 0-4.

In vitro solubility tests of granulated materials and coatings were carried out on some compositions in the system CaTi(x)Zr4-(x)(PO4)6 with x = 0-4, in order to find a biocompatible material which is less soluble than hydroxyapatite (HA) and can also be used as bone substitution material. The granulated materials were leached out by using circulating equipment in which the solvent flows in circulation. The coatings were tested under conditions where the sample containers undergo a circular movement. The results show better chemical stability of nearly all tested compounds compared with HA for both granulated materials and coatings.

Biocompatible Materials↗

Anterior cervical fusion with polyetheretherketone (PEEK) cages in the treatment of degenerative disc disease. Preliminary observations in 36 consecutive cases with a minimum 12-month follow-up.

STUDY DESIGN: Retrospective analysis of 36 cases of degenerative disc disease treated by interbody fusion with polyetheretherketone (PEEK) cages. OBJECTIVE: To determine the safety and efficiency of PEEK cages for anterior cervical fusion (ACF). SUMMARY OF BACKGROUND DATA: ACF with autologous bone has been reported since over 50 years ago. The recent development of cages housing materials inducing osteogenesis simplifies the technique of interbody fusion. The main purposes of bone substitutes for ACF are immediate biomechanical support, osteo-integration of the graft, and elimination of local side effects at the donor site. This report shows our results using PEEK cages. MATERIALS AND METHODS: During an 18-month period, 36 consecutive patients had cervical fusions at 43 levels between C3 and C7. All operations involved one or two disc spaces for degenerative disc disease. We implanted all disc spaces with PEEK cages (Stryker Corporation, Kalamazoo, MI) containing granulated coralline hydroxylapatite (Pro-Osteon 200, Interpore Cross International, Irvine, CA) or deantigenated pig bone in a gel solution (Gen-Os, Tecnoss, Torino, Italy). RESULTS: About 97% of patients had a good to excellent outcome; the result in one myelopathic patient was fair. The cervical fusion rate was 16.7% at 3 months, 61.1% at 6 months, and 100% at one year. CONCLUSIONS: PEEK cages appear to be safe and efficient for ACF. In order to confirm our preliminary impressions studies on larger series with long term follow-up are warranted.

Adult↗

Action of FGMgCO3Ap-collagen composite in promoting bone formation.

To improve the biological properties of materials as bone substitutes, functionally graded CO3 apatite crystals containing magnesium, FGMgCO3Ap, were synthesized to be mixed with atelocollagen and made into a composite pellet. A radio-labeled cell adhesion experiment showed that the degree of adherence of mouse MC3T3E1 osteoblast-like cells to the FGMgCO3Ap-collagen composite was better than to CO3Ap-collagen and much better than to the Ti plate. When the composites were implanted beneath the periosteum cranii of rats, the FGMgCO3Ap-collagen composite was metabolized faster than the CO3Ap-collagen composite and better formation of new bone and osteoblast arrangement at the interface between the composite and the periosteum cranii was observed. When the composites were implanted into the femur of rabbits, clear bone formation with a higher degree of bone density was observed for the FGMgCO3Ap-collagen composite. These results suggest that the Mg2+ ions taken into the apatite crystals may contribute to the acceleration of osteoblast adhesion to apatites and promote bone formation, cross-talking with osteoblasts at the molecular level.

3-Hydroxysteroid Dehydrogenases↗

Synthesis of osteoconductive organic inorganic nanohybrids through modification of chitin with alkoxysilane and calcium chloride.

The so-called bioactive ceramics have been attractive because they spontaneously bond to living bone. Organic-inorganic hybrids consisting of organic polymers and the essential constituents of the bioactive ceramics, i.e., silanol (Si-OH) group and calcium ions (Ca(2+)), are useful as novel bone substitutes, owing to bioactivity and high flexibility. In the present study, organic-inorganic hybrids are synthesized from chitin by modification with glycidoxypropyltrimethoxysilane (GPS) and calcium chloride (CaCl(2)). Their apatite-forming ability is examined in a simulated body fluid (SBF). The prepared hybrids form apatite on their surfaces in SBF within 7 days.

Apatites↗

Effects of pretreatment clinical parameters on bioactive glass implantation in intrabony periodontal defects.

BACKGROUND: The various methods for regeneration of periodontal tissue that have been developed can be classified into guided tissue regeneration and bone implantation. Since the implantation materials have shown both deficiencies and merits, dentists have begun exploring the bioactive glass first used in plastic surgery. This paper examines the effectiveness of this new material on periodontal intrabony defects. METHODS: Clinical effects of bioactive glass implantation in intrabony periodontal defects were evaluated 6 months after surgery in 38 intrabony defects from 38 patients with chronic periodontitis. Twenty-one experimental defects received bioactive glass implantation (test group), while 17 control defects were treated with a flap procedure only (control group). The criteria for comparative observation were preoperative and postoperative probing depth (PD), clinical attachment level (CAL), bone probing depth (BPD), and gingival recession. RESULTS: Reductions in PD were observed in both groups (P<0.01). The reduction in PD was significantly greater in the test group when preoperative PD exceeded 7 mm (P<0.01). Improvements in CAL were also observed in both groups (P<0.01), with the test group showing significantly greater gains (P<0.05). In those cases where preoperative CAL was less than 7 mm, there was no statistically significant difference between the two groups. Reduction in BPD was observed in both groups, with the test group showing significantly greater reduction (P <0.01). There was no significant difference in BPD change, however, when preoperative BPD was < or =7 mm. Significantly greater reduction of BPD in the test group was observed when intrabony defect depth was >4 mm (P <0.05). Significant improvements in PD, CAL, and BPD were noted in the test group when the crestal involvement exceeded 100 degrees. Correlation test between various clinical parameters indicated that greater changes in PD and CAL in the test group were observed when preoperative CAL was large (P<0.001), and greater changes in PD (P<0.05), CAL (P<0.01), and BPD (P<0.05) were noted when preoperative BPD was large. Correlation between crestal involvement and CAL change was noted only in the control group (P<0.01). High correlations were observed between PD changes and CAL changes and between CAL changes and BPD changes in both groups. CONCLUSIONS: Use of a bone substitute in a flap operation resulted in significantly greater improvements in CAL and BPD over flap operation alone and seemed to have positive effects in postoperative PD, CAL, and BPD in those cases with more severe preoperative CAL and BPD.

Adult↗

A new simplified technique for producing platelet-rich plasma: a short technical note.

A possible strategy to promote the wound-healing cascade in both soft and hard tissues is the preparation of an autologous platelet-rich plasma (PRP) to encourage the release of growth factors from activated platelets. In this process, PRP combines the advantage of an autologous fibrin clot that will aid in hemostasis as well as provide growth factors in high concentrations to the site of a tissue defect. The PRP preparation can be used as a biological enhancer in the healing of fractures and lumbar fusions. The local application of growth factors seems to promote initiation and early maturation of bone formation. Autologous bone or bone substitutes can be added to this mixture to increase the volume of grafting material. A simplified technique utilizing a commercially available separation system (GPS-Gravitational Platelet Separation System) is described. This system provides a less costly alternative to other previously described augmentation techniques and also presents a patient-friendly and operator-safe alternative. Further experimental studies of the actual concentrations of the growth factors in the PRP samples are necessary in order to validate the platelet concentration and growth-factor activation by laboratory evidence. In further prospective clinical trials, the safety and efficacy of PRP, in combination with autologous bone or bone graft substitutes, must be evaluated.

Blood Loss, Surgical↗

Calcium orthophosphates in medicine: from ceramics to calcium phosphate cements.

Calcium phosphate (CaP) compounds are becoming of increasingly great importance in the field of biomaterials and, in particular, as bone substitutes. Recent discoveries have accelerated this process, but have simultaneously rendered the field more complicated for the everyday user. Subtle differences in composition and structure of CaP compounds may have a profound effect on their in vivo behaviour. Therefore, the main goal of this article is to provide a simple, but comprehensive presentation of CaP compounds. Reference is made to the most important commercial products.

Biodegradation, Environmental↗

Bone growth into a ceramic-filled defect around an implant. The response to transforming growth factor beta1.

Synthetic bone substitutes provide an alternative to autograft but do not give equivalent clinical results. Their performance may be enhanced by adding osteogenic growth factors. In this study, TGFbeta1 was absorbed on to a carrier of beta tricalcium phosphate and Gelfoam and used to fill a defect around a tibial implant in a rat model of revision arthoplasty. We added 0.0, 0.02 microg, 0.1 microg or 1.0 microg of TGFbeta1 to the carrier and then implanted it around an hydroxyapatite-coated stainless-steel pin in the proximal tibia of rats. The tibiae were harvested at three, six or 26 weeks and the amount of bone formation and ceramic resorption were assessed. TGFbeta1 had no effect on the amount of bone in the defect, the amount of fluorescent label incorporated or the rate of mineral apposition. The growth factor did not significantly affect the amount of betaTCP remaining in the tissue at any of the time points.

Animals↗

Poly(D, L-lactide/epsilon-caprolactone)/hydroxyapatite composites as bone filler: an in vivo study in rats.

In this study, a novel composite bone substitute was implanted in animal models (rats) and their in vivo characteristics were examined. A D,L-lactide and E-caprolactone copolymer (Mw: 80,000; Mn:40,000, and PI:2.00) was synthesized by ring-opening polymerization of the respective dimers using stannous octoate as the catalyst. The final ratio of D,L-lactide to epsilon-caprolactone obtained by 1NMR was 60/40. Hydroxyapatite (HA) powder was loaded in the copolymer. The HA/copolymer ratio was 60/40 (w/w). These composites were easily shaped by hand. Animal tests were performed on mature wistar rats (n=30). Defects were created on the proximal, the thickest part of the femur. The bone defects of the first group were filled with polymer/HA composite, the second group filled with only HA and the third group was left empty. Histologic examination of bone tissues showed new bone formation around the yellow-green polymer/HA composite material in the first group of animals whereas no evidence of new bone growth was observed in other groups.

Animals↗

Hybrid composites of calcium phosphate granules, fibrin glue, and bone marrow for skeletal repair.

Synthetic bone substitutes, such as calcium phosphate ceramics, give good results in clinical applications. In order to adapt to surgical sites, bioceramics come in the form of blocks or granules, and are either dense or porous. Combining these bioceramics with fibrin glue provides a mouldable and self-hardening composite biomaterial with the biochemical properties of each component. Critical-sized defects in the femoral condyle of rabbits were filled with TricOs/fibrin glue/bone marrow hybrid/composite material. The TricOs granules (1-2 mm) were composed of hydroxyapatite and beta tricalcium phosphate (60/40 in weight). The fibrin glue was composed of fibrinogen, thrombin and other biological factors and mixed with MBCP granules either simultaneously or sequentially. Bone marrow was also added to the MBCP/fibrin composite prior to filling the defects. After 3, 6, 12, and 24 weeks of implantation, the newly-formed bone was analysed with histology, histomorphometry and mechanical tests. The newly-formed bone had grown centripetally. Simultaneous application of fibrin glue showed better results for mechanical properties than sequential application after 6 weeks. Around 40% of bone had formed after 24 weeks in the three groups. Although the addition of bone marrow did not improve bone formation, the MBCP/fibrin material could be used in clinical bone filling applications.

Animals↗

Biologic enhancement of spinal fusion.

STUDY DESIGN: Literature review. OBJECTIVES: To review the available animal and clinical data on biologic enhancements of spinal fusion. SUMMARY OF BACKGROUND DATA: Lumbar spinal arthrodesis may result in pseudarthrosis in 5% to 35% of patients. Although much research has focused on the mechanical factors affecting spinal fusion, the use of internal fixation has not eliminated the problem of spinal nonunions. Accordingly, biologic enhancement of spinal fusion has become an important focus of spinal research. METHODS: Medline and hand searches. RESULTS: Electric stimulation, bone graft substitutes, and bone growth factors have been researched most extensively. Electric stimulation and early attempts at bone graft substitutes (allograft, xenograft) have yielded variable results. The feasibility of biologic enhancement of spinal fusion with osteoinductive growth factors has been shown in animals. CONCLUSION: The efficacy of bone growth factors for lumbar fusion remains to be definitively established in humans.

Animals↗

Three-dimensional defects in hydroxyapatite of biological interest.

Hydroxyapatite (HA) ceramics are widely used as bone substitutes in the repair of bony defects. These ceramics sometimes differ in their sintering temperatures. High resolution transmission electron microscopy was used to characterize HA ceramics sintered at different temperatures. A new type of defect was observed for the first time for ceramics prepared at 900 degrees C but not on those prepared at 1250 degrees C. This may cause a difference in their in vitro dissolution and in vivo performance.

Animals↗

rhBMP-2 delivered in a calcium phosphate cement accelerates bridging of critical-sized defects in rabbit radii.

BACKGROUND: Treatment of segmental bone loss remains a challenge in skeletal repairs. This study was performed to evaluate the efficacy of the use of recombinant bone morphogenetic protein-2 (rhBMP-2) delivered in an injectable calcium phosphate cement (alpha bone substitute material [alpha-BSM]) to bridge critical-sized defects in the rabbit radius. METHODS: Unilateral 20-mm mid-diaphyseal defects were created in the radii of thirty-six skeletally mature New Zealand White rabbits. The defects in twelve rabbits each were filled with 0.166 mg/mL rhBMP-2/alpha-BSM cement, 0.033 mg/mL rhBMP-2/alpha-BSM cement, or buffer/alpha-BSM cement. Six rabbits from each group were killed at four weeks, and six were killed at eight weeks. Serial radiographs were made to monitor defect-bridging and residual alpha-BSM carrier. A semiquantitative histological scoring system was used to evaluate defect-bridging. Histomorphometry was used to quantify residual alpha-BSM; trabecular bone area; trabecular bone volume fraction; and cortical length, width, and area. RESULTS: At four weeks, there had been more rapid resorption of alpha-BSM and filling of the defects with trabecular bone in the group treated with 0.166 mg/mL rhBMP-2/alpha-BSM than in the other two groups. Histomorphometry confirmed an increased trabecular area and volume fraction in this group compared with the other two groups. In both rhBMP-2/alpha-BSM-treated groups, the majority of the trabecular bone was formed by a direct process adjacent to the resorbing alpha-BSM. At eight weeks, complete cortical bridging and regeneration of the marrow space were present in all of the defects treated with 0.166 mg/mL rhBMP-2/alpha-BSM. That group also had reduced residual alpha-BSM and trabecular area and volume, compared with the other two groups, at eight weeks as a result of a rapid remodeling process. CONCLUSIONS: Treatment of a critical-sized defect in a rabbit radius with 0.166 mg/mL rhBMP-2/alpha-BSM injectable cement can result in bridging with cortical bone and a regenerated bone-marrow space by eight weeks. Site-specific remodeling appears to be responsible for corticalization and marrow regeneration. CLINICAL RELEVANCE: RhBMP-2 delivered in a calcium phosphate cement may be useful to achieve bridging of critical-sized defects in patients. Its injectable properties may allow minimally invasive use. Delayed percutaneous administration would also be possible when augmentation is desired following an initial surgical procedure or when soft-tissue injuries preclude adequate initial treatment.

Animals↗