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[Bone regeneration in Pro Osteon 500 alone and in combination with Colloss in the patellar gliding model of the rabbit].

In order to optimize osteoneogenesis, Pro Osteon 500 (coralline hydroxylapatite) was coated with the osteoinductive protein complex Colloss and implanted in distal rabbit femurs for 28, 84, 168, and 365 days. Uncoated material was placed contralaterally and examined for intraindividual control. No impairment of bone formation on the implant granules was noted upon histological examination, as well as after coating with Colloss. Both osteoid and chondroid were sparsely found. After 84 days the original woven bone had been largely transformed into lamellar bone. Formation of new bone increased up to 84 days and from then on ranged from 49.8% to 58.7% up to 365 days. This increase was independent of the lower density of the cancellous bone surrounding the graft. Coating with Colloss promoted osteoneogenesis to a maximum of 15.1%, which, however, was not statistically significant. The implant granules were not subject to resorption.

Animals↗

Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration.

Based on a new concept, a procedure combining induced membranes and cancellous autografts allows the reconstruction of wide diaphyseal defects. In the first stage of this procedure, a cement spacer is inserted into the defect; the spacer is responsible for the formation of a pseudo-synovial membrane. In the second stage, the defect is reconstructed two months later by an autologous cancellous bone graft. The aim of this study was to evaluate the histological and biochemical characteristics of these membranes induced in rabbits. Histological studies carried out two, four, six, and eight weeks following implantation revealed a rich vascularization. Qualitative and quantitative immunochemistry showed production of growth factors (VEGF, TGFbeta1) and osteoinductive factors (BMP-2). Maximum BMP-2 production was obtained four weeks after the implantation, and, at this time, induced membranes favored human bone marrow stromal cell differentiation to the osteoblastic lineage. Should these results be confirmed in humans, bone reconstruction could be carried out earlier than previously thought and in better conditions than expected, the membrane playing the role of an in situ delivery system for growth and osteoinductive factors.

Animals↗

[Animal experimental studies on bone regeneration after the implantation of heteroplastic materials].

The healing of standardized bony defects in the region of the mandible following implantation of various heterologous bony components was controlled in animal experiments via polychromatic sequential labeling. The implant of gelatin foam did not accelerate healing. The combination of gelatin and solcoseryl led to accelerated mineralization in the marginal area. Mature collagen affected rapid healing of the bony defect, as did the implantation of a combination of Solcoseryl and bone meal.

Actihaemyl↗

[Destructive and reparative processes after UHF and cryo-effect on bone regeneration in dogs].

The experiment was carried out on the lower jaw of mongrel dogs. It included 36 observations on the basis of the morphological method. The aim is to study the effectiveness of the effect of cold and the combination of the UHF radiation on the proliferative reaction of cells of the lower jaw. It was proved that under the influence of cold the skeletogenic tissue undergoes changes. The combination of cold with UHF radiation cause less destructive cold effects on the bone tissue away from the injury of resorption. Hence the effect of cold on the proliferating tissue causing its necrosis proves the possibility of its use in removal of tumours, substituting wide caving around them by more protective intervention: the combination of carving of tumour with the cryodestruction of tissue around it. In such a combination the reparative processes become more effective, which enables us to recommend them for clinical use for curing benign tumour.

Animals↗

Synthesis of calcium-phosphate and chitosan bioceramics for bone regeneration.

Bioceramic composites were obtained from chitosan and hydroxyapatite pastes synthesized at physiological temperature according to two different syntheses approaches. Usual analytical techniques (X-ray diffraction analysis, Fourier transformed infrared spectroscopy, Thermo gravimetric analysis, Scanning electron microscopy, X-ray dispersive energy analysis and Porosimetry) were employed to characterize the resulting material. The aim of this investigation was to study the bioceramic properties of the pastes with non-decaying behavior from chitosan-hydroxyapatite composites. Chitosan, which also forms a water-insoluble gel in the presence of calcium ions, and has been reported to have pharmacologically beneficial effects on osteoconductivity, was added to the solid phase of the hydroxyapatite powder. The properties exhibited by the chitosan-hydroxyapatite composites were characteristic of bioceramics applied as bone substitutes. Hydroxyapatite contents ranging from 85 to 98% (w/w) resulted in suitable bioceramic composites for bone regeneration, since they showed a non-decaying behavior, good mechanical properties and suitable pore sizes.

Biocompatible Materials↗

Fast-setting calcium phosphate scaffolds with tailored macropore formation rates for bone regeneration.

Calcium phosphate cement (CPC) is highly promising for craniofacial and orthopedic repair because of its ability to self-harden in situ to form hydroxyapatite with excellent osteoconductivity. However, its low strength, long hardening time, and lack of macroporosity limit its use. This study aimed to develop fast-setting and antiwashout CPC scaffolds with high strength and tailored macropore formation rates. Chitosan, sodium phosphate, and hydroxypropyl methylcellulose (HPMC) were used to render CPC fast-setting and resistant to washout. Absorbable fibers and mannitol porogen were incorporated into CPC for strength and macropores for bone ingrowth. Flexural strength, work-of-fracture, and elastic modulus were measured vs. immersion time in a physiological solution. Hardening time (mean +/- SD; n = 6) was 69.5 +/- 2.1 min for CPC-control, 9.3 +/- 2.8 min for CPC-HPMC-mannitol, 8.2 +/- 1.5 min for CPC-chitosan-mannitol, and 6.7 +/- 1.6 min for CPC-chitosan-mannitol-fiber. The latter three compositions were resistant to washout, whereas the CPC-control paste showed washout in a physiological solution. Immersion for 1 day dissolved mannitol and created macropores in CPC. CPC-chitosan-mannitol-fiber scaffold had a strength of 4.6 +/- 1.4 MPa, significantly higher than 1.2 +/- 0.1 MPa of CPC-chitosan-mannitol scaffold and 0.3 +/- 0.2 MPa of CPC-HPMC-mannitol scaffold (Tukey's). The strength of CPC-chitosan-mannitol-fiber scaffold was maintained up to 42 days and then decreased because of fiber degradation. Work-of-fracture and elastic modulus showed similar trends. Long cylindrical macropore channels were formed in CPC after fiber dissolution. The resorbable, fast-setting, anti-washout and strong CPC scaffold should be useful in craniofacial and orthopedic repairs. The novel method of combining fast- and slow-dissolution porogens/fibers to produce scaffolds with high strength and tailored macropore formation rates to match bone healing rates may have wide applicability to other biomaterials.

Bone Regeneration↗

Transcriptional profiling of bone regeneration. Insight into the molecular complexity of wound repair.

The healing of skeletal fractures is essentially a replay of bone development, involving the closely regulated, interdependent processes of chondrogenesis and osteogenesis. Using a rat femur model of bone healing to determine the degree of transcriptional complexity of these processes, suppressive subtractive hybridization (SSH) was performed between RNA isolated from intact bone to that of callus from post-fracture (PF) days 3, 5, 7, and 10 as a means of identifying up-regulated genes in the regenerative process. Analysis of 3,635 cDNA clones revealed 588 known genes (65.8%, 2392 clones) and 821 expressed sequence tags (ESTs) (31%, 1,127). The remaining 116 cDNAs (3.2%) yielded no homology and presumably represent novel genes. Microarrays were then constructed to confirm induction of expression and determine the temporal profile of all isolated cDNAs during fracture healing. These experiments confirmed that approximately 90 and approximately 80% of the subtracted known genes and ESTs are up-regulated (> or = 2.5-fold) during the repair process, respectively. Clustering analysis revealed subsets of genes, both known and unknown, that exhibited distinct expression patterns over 21 days (PF), indicating distinct roles in the healing process. Additionally, this transcriptional profiling of bone repair revealed a host of activated signaling molecules and even pathways (i.e. Wnt). In summary, the data demonstrate, for the fist time, that the healing process is exceedingly complex, involves thousands of activated genes, and indicates that groups of genes rather than individual molecules should be considered if the regeneration of bone is to be accelerated exogenously.

Animals↗

Guided bone regeneration with beta-tricalcium phosphate and poly L-lactide-co-glycolide-co-epsilon-caprolactone membrane in partial defects of canine humerus.

This study was performed to evaluate the effect of betatricalcium phosphate and poly L-lactide-co-glycolide-coepsilon- caprolactone (TCP/PLGC) membrane in the repair of partial bone defects in canine proximal humerus. Three adult mixed-breed dogs were used during the experimental period. The length of the defect was quarter of the full length of humerus, and width of the defect was quarter of middle diameter of the lateral aspect of humerus. The humeri of each dog were divided into treatment (TCP/ PLGC) and control groups. The defect was covered with TCP/PLGC membrane in treatment group. To evaluate regeneration of the bone, computerized tomography (CT) and histopathologic examination were performed. The radiopaque lines were appeared at the original defect sites in TCP/PLGC group but below the original site in control at 4th week. Radiopacity and thickness of the defect sites, and radiopaque lines were more increased at 8th week than those of 4th week. Histopathologic findings revealed fibrous connective tissue migration into the defect and the migration inhibited the structure of new cortex to be placed in the original level in control whereas new cortex growth was found in the level of original line in TCP/ PLGC group. However, the new cortical bone in the TCP/ PLGC group was thinner and less organized than the adjacent intact cortex, and the amount of new cancellous bones were also scanty. The result suggested that TCP/ PLGC membrane is a good guided bone regeneration material to restore the original morphology of humerus in partial defect.

Absorbable Implants↗

Guided bone regeneration for immediate non-submerged implant placement using bioabsorbable materials in Beagle dogs.

The aim of the present study was to evaluate the combined application of different bioabsorbable materials for healing of residual peri-implant defects after placement of non-submerged implants into fresh extraction sockets. Second and third mandibular premolars were extracted from 10 Beagle dogs, the coronal part of the distal sockets were surgically enlarged and this was followed by immediate placement of specially designed hollow-screw non-submerged dental implants. For each animal, the coronal peri-implant defects were further treated with one of the 4 following procedures: 1) no treatment, control site; 2) grafting with porous hydroxyapatite (HA); 3) collagen membrane tightly secured around the implant and over the defect and 4) grafting with HA covered with a collagen membrane. After 16 weeks of healing, specimens were removed from the mandibule and prepared for a histomorphometric evaluation. The bone-to-implant contact length (BIC) was measured and compared amongst the different treatment modalities. In the defect area, the irregular bone regeneration was similar between all the treatment procedures (P > 0.10). In the sites covered with a collagen membrane alone, the total BIC (47%) was greater than in control sites (28.7%, P < 0.05) or sites grafted with HA (22.2%, P < 0.02). Total BIC in sites treated with the HA-membrane combination (43%) was only significantly different from sites treated with HA (P < 0.05). It is concluded that the use of bioabsorbable materials results in a limited increase of osseointegration when used in conjunction with immediate placement of non-submerged implants, although the principle of the one stage surgical approach can be maintained.

Absorbable Implants↗

[Normalization of bone regeneration by oxygen barotherapy].

Experimental studies in 60 rabbits with defects of the radius have shown that exposure to oxygenobarotherapy results in the greatest activization of osteoreparation in the early period after trauma with the formation of osseous matrix. The intensity of OBT sessions should be reduced along with the "maturation" of the osseous regenerate. The clinical application of OBT in 33 patients with defects of long tubular bones contributed to shortening the terms of rehabilitation of such patients.

Animals↗

Effect of adding resorbable calcium sulfate to grafting materials on early bone regeneration in osseous defects in rabbits.

This experiment was designed to study the osteogenic potential of adding medical-grade resorbable calcium sulfate mixture to grafting materials for filling osseous defects. Twelve New Zealand rabbits were divided into an active group of 10 animals and a control group of 2 animals. The median condyle of each femur was drilled to create 8-mm-deep cavities. Active osseous defects consisted of 20 cavities and were filled with Osteograf, BOP, or Capset (calcium sulfate) alone; a mixture of Osteograf and Capset; or a mixture of BOP and Capset. Osteograf and BOP were each mixed with Capset in a 4:1 ratio. Each grafting material filled 4 osseous cavities, and 4 osseous cavities were left unfilled to act as controls. The observation period was 8 weeks. Block sections of the femoral heads were prepared for decalcified histologic assessment. It appeared that mixing grafting materials with calcium sulfate powder in a 4:1 ratio, respectively, facilitated the process of osteogenesis and increased new bone bonding to remnants of the grafting materials, in spite of the poor osteoconductive property of BOP and moderate osteoconductivity of Osteograf. However, calcium sulfate material alone is not recommended for use as a bone filler.

Absorbable Implants↗

An osteoconductive collagen/hyaluronate matrix for bone regeneration.

A new type of collagen-hyaluronate (COL/HA) matrix was synthesized by cross-linking collagen fibers with modified hyaluronate polymers bearing active formyl groups. The resulting matrix is a three-dimensional scaffold consisting of interconnected pores with an average size of 40 microm and a high pore volume/surface area ratio. The covalent nature of the bond between the collagen fibers and the modified hyaluronate was demonstrated by extended elution with phosphate buffered saline and by extraction in increasing ionic gradients. The fraction of covalently bound hyaluronate in the matrix ranged from 5 to 25 w%. The total hyaluronate content of the COL/HA matrix affected both the in vitro non-enzymatic and enzymatic degradation as well as the in vivo turnover. When implanted in cranial defects in rats, the COL/HA matrix demonstrated good biocompatibility and exhibited greater osteoconductive potential than matrices composed of either cross-linked collagen or cross-linked hyaluronate alone.

Animals↗

New macroporous calcium phosphate glass ceramic for guided bone regeneration.

This work describes a method to obtain macroporous resorbable glass and glass ceramic scaffolds with controlled biodegradability for tissue engineering applications. The constructs consisted of glass and glass ceramics in the system P(2)O(5)-CaO-Na(2)O-TiO(2) and they were prepared by foaming a slurry of glass particles by addition of a H(2)O(2) solution, and subsequent sintering of the porous structures obtained. Different thermal treatments were applied to control the degree of devitrification of the glass. The resultant materials showed a porosity percentage between 40% and 55% with a wide variety of pores ranging from 20 to 500 microm in diameter as determined by SEM and Image Analysis. The resulting constructs were predominantly formed by a vitreous phase, although small amounts of calcium metaphosphate and pyrophosphates were detected by X-ray diffraction and Raman spectroscopy after the sintering process. The biological response was also evaluated by means of the MTT test, the material showed a non-cytotoxic effect.

Absorbable Implants↗