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Bioceramics as an option in correction of facial skeleton deformities.

The removal of certain deformities of facial bones is a prerequisite to a restoration of function, stability, and appearance. Synthetic bone substitutes are beneficial in cases where other operative technique would represent an inadequate burden for a patient. A result is achieved in one surgical intervention with low costs and low demands on technical equipment. Biocompatible nonresorbable glass-ceramics based on oxyfluoroapatite and wollastonite presenting osteoconductivity permits osteointegration, i.e., direct physicochemical bonds between live bone tissue and the implant without formation of a fibrous capsule. It presents better durability to stress in simulated body fluid than the usually used hydroxyapatite. It was used for restoration of facial skeletal framework contour in 14 cases under conditions where prior solutions were doubtful. Good results were reached in all patients. The mean time of observation was 18 months. During that period, the rate of complications was 14.3%. This approach may be found to be a suitable technique, especially for patients exhausted by prior unsuccessful treatment but still not acquiesced in a result.

Adult↗

[Experimental study on the reconstruction of bone defects in vivo and the osteoinduction with degradation products of alpha-tricalcium phosphate cements in vitro].

OBJECTIVE: This study was aimed to clarify the characteristics of alpha-tricalcium phosphate cements in reconstructing bone defects and the action of degradation products of cements in vitro. METHODS: The defect (diameter 1.5 cm) was created in the calvaria of rabbit. Alpha-tricalcium phosphate cements were planted in the treatment groups. All groups were observed by histological examination and roentgenography. Bone marrow stromal cells (BMSc) were cultured in the degradation products of cements in vitro, and were observed by means of cytology and ALP. RESULTS: Degradation of artificial bone, new bone formation, and osteogenesis between artificial bone particles were observed at 12 weeks after implantation. Osteoinduction was observed in vitro. CONCLUSION: Alpha-tricalcium phosphate cements have good biocompatibility, osteoinductivity and degradability, and are ideal bone substitute material for reconstruction.

Animals↗

Mechanical and biocompatible influences of chitosan fiber and gelatin on calcium phosphate cement.

Calcium phosphate cement (CPC) is a widely used bone substitute in the clinic; however, the low strength of CPC limits its utilization. In this study, we investigated mechanical influences of chitosan fiber combined with gelatin on CPC, and examined the biocompatibility of the new composite with rat bone marrow stromal cells. Compared to the fiber impregnated in phosphate buffered saline (80.5 MPa), our study showed that tensile strength of chitosan fiber increased 106 and 114% with the impregnation of gelatin at the mass fraction 5 and 10%, although this increase was not statistically significant. It was demonstrated by Fourier transform infrared spectroscopy that the characteristic absorption bands of chitosan were changed with the addition of gelatin. The optimal flexural strength enhancement was obtained when CPC was reinforced with fiber at volume fraction of 30% and gelatin at mass fraction of 5% (maximum: 12.31 MPa). The fiber morphology was more compact when the chitosan fibers impregnated with gelatin at mass fraction of 5 or 10% than chitosan alone. The fracture analysis showed that the new CPC-chitosan fiber-gelatin composite presented many remnants of CPC adhered to fibers. Short minimum essential medium extract test showed no cell growth inhibition after the addition of the new composite. Rat bone marrow stromal cells retain the ability to spread and grow on the composite. Our studies demonstrated that the flexural strength is greatly increased by using CPC incorporated with proper ratio of CF and gelatin. More over, the new composite demonstrated biocompatibility in vitro.

Animals↗

Ceramic drug delivery: a perspective.

Different ceramic substances are offered in the market as bone substitute materials. These include monophasic calcium phosphate ceramics of tricalciumphosphate (TCP) or hydroxyapatite (HA), biphasic calcium phosphate ceramics and multiphasic bio-glasses synthetic calcium phosphate cements. Ceramics with appropriate three-dimensional geometry are able to bind and concentrate bone morphogenetic proteins in circulation and may become osteoinductive (capable of osteogenesis) and can be effective carriers of bioactive peptide or bone cell seeds and are therefore potentially useful in tissue engineering and drug delivery. An attempt has been made to review various drug delivery applications of ceramics.

Biocompatible Materials↗

A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics.

With respect to the effect of material factors on calcium phosphate biomaterial-induced osteogenesis, the osteoinductive property of two kinds of porous hydroxyapatite ceramics, which were made by different producers, was investigated in dorsal muscles of dogs. One hydroxyapatite ceramic (S-HA), macroporous implants with rough pore walls containing abundant micropores, was made by Sichuan Union University (Chengdu, China); the other hydroxyapatite ceramic (J-HA), porous implants with smooth macropore walls composed of regularly aligned crystal grains, was provided by Mitsubishi Ceramic Int. (Japan). Different tissue response was detected histologically and microradiographically after the ceramic samples had been implanted in dorsal muscles of dogs for 3 and 6 months. Bone formation was found in S-HA at 3 months, which increased at 6 months. In contrast, no bone formation was detected in J-HA at both 3 and 6 months. These results indicate that with the special architecture, calcium phosphate ceramic can induce bone formation in soft tissue. As both materials were very similar in their chemical and crystallographic structures, but varied in their microstructures, the latter seem to be an important factor affecting the osteoinductive capacity of calcium phosphate ceramics. These data suggest that, by controlling the preparation of calcium phosphate ceramic, bone substitutes with intrinsic osteoinductive property can be developed from calcium phosphates.

Animals↗

Synthesis of functionally graded MgCO3 apatite accelerating osteoblast adhesion.

As a means of improving the biological properties of materials for use as bone substitutes, functionally graded carbonate apatite containing Mg, FGMgCO3Ap, was synthesized at 60 degrees C and pH 7.4 using a gradient magnesium supply system. X-ray diffraction analysis of FGMgCO3Ap showed a poorly crystallized apatitic pattern, similar to that of human bone. ESCA analysis clearly showed the negative gradient distribution in Mg1s intensity (atomic concentration) of magnesium from the crystal surface toward the inner core. When the FGMgCO3Ap crystals were mixed with collagen, the resulting FGMgCO3Ap-collagen composite, irradiated with UV light for 4 h, retained their features in the saline solution. After washing away the nonadhesive cells, a cell adhesion assay showed that the optical density of the FGMgCO3Ap-collagen composite was higher than that of the CO3Ap-collagen composite. SEM observation showed that the osteoblast-like cells adhered well to the surface of the FGMgCO3Ap-collagen composite. Staining with hematoxylin-eosin and alizarin red confirmed the existence of a great many more cells and a thicker extracellular matrix layer on the FGMgCO3Ap-collagen composite than on the CO3Ap-collagen composite. This result demonstrated the acceleration effect of magnesium ions on osteoblast adhesion on the FGMgCO3Ap-collagen composite.

Animals↗

Effect of calcium, zinc and magnesium on the attachment and spreading of osteoblast like cells onto ceramic matrices.

Calcium phosphate ceramic has been widely used as bone substitute materials. Neumerours approaches have been investigated to develop tissue-engineered scaffold from hydroxyapatite because of its advantages like osteoconduction. We have developed porous ceramic matrices from nanoparticles of calcium phosphate containing zinc and magnesium. Mimicking the grain size of natural bone enhances the bone forming function of cells. Osteoblast-like MG63 cells were cultured on to these porous ceramic matrices. Cell adhesion and spreading onto these matrices were studied for 24 h and 5 days in vitro. It was observed that on calcium phosphate matrix, containing a combination of zinc and magnesium, the osteoblast adhesion and spreading was significant on 5th day. This appeared to be comparable to the hydroxyapatite control. This makes it a promising candidate as a bone tissue-engineering scaffold.

Bone Substitutes↗

Bone formation following guided tissue regeneration (GTR).

The principle of guided tissue regeneration using barrier membranes has become an accepted method for the treatment of teeth with severe osseous defects and furcation involvement. A technique was developed using an expanded polytetrafluoroethylene soft-tissue patch, 1 mm thick (W.L. Core and Assoc., Flagstaff, AZ), in conjunction with an alloplast hydroxyapatite bone substitute (HA-500, 40-60 mesh) (Orthomatrix, Minneapolis, MN), for space maintenance in severe osseous defects. A case report is presented which demonstrates the successful use of this method, and includes a fourth-year re-entry procedure that illustrates the complete bone fill and obturation of a severe vertical defect and Class II furcation of a mandibular first molar.

Aged↗

Advances in cranioplasty with osteoinductive biomaterials: summary of experimental studies and clinical prospects.

The surgical repair of large calvarial defects is still a challenge for craniofacial surgeons. Since the discovery of bone growth factors, numerous studies have confirmed the interest of osteoinduction for bone repair. We summarize the findings of experimental and clinical trials carried out with composite bone substitutes. The triple mixture of TGF-beta 1, fibrin glue, and natural coral has proven effective in repairing rabbit skull defects. The same preparation was also efficient for a cranioplasty in two of three patients, age being a limiting factor. The adjunction of bone morphogenetic protein to autologous bone marrow was shown to be a potentiating factor in a rat cranioplasty model, but the combination of fibrin glue and bone marrow on a natural coral carrier was unable to achieve bone repair in children aged 6 years. Although the series were limited, stability and asepsis were important factors in promoting bony ingrowth. Cranioplasties with osteogenic biomaterials may be good option, but the most adequate dose of growth factor should be determined.

Adolescent↗

Mechanical properties and biological behavior of carbon nanotube/polycarbosilane composites for implant materials.

Multiwalled carbon nanotube/polycarbosilane (MWCNT/PCS) composites were fabricated by the spark plasma sintering (SPS) method. The MWCNT/PCS composites consisted of MWCNTs and nanosized SiC particles pyrolyzed from PCS and possessing good mechanical properties for bone tissue repair or dental implantation. The MWCNT/PCS composites were implanted in the subcutaneous tissue and femur of rats at 1 and 4 weeks after implantation. Histological investigations showed that there was little inflammatory response in the subcutaneous tissue, and newly formed bone tissue was observed in the femur. These results indicated that the MWCNT/PCS composite had little prophlogistic effect and good osteoconductivity. The study suggested the possibility that the MWCNT/PCS composite could be a candidate bone-substitute and dental-implant material in the future.

Animals↗

Effect of recombinant human bone morphogenetic protein-2 on bone formation in alveolar ridge defects in dogs.

This study was designed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) on the formation of bone in critically sized marginal defects of the mandible in dogs. Three months after extraction of the pre-molar teeth, rectangular bone defects (10 x 8 x 7 mm) were made in both sides of the mandible. A PGS block soaked in rhBMP-2 (400 microgram/ml) was implanted into one defect (BMP (+) group). As control, an untreated PGS block was implanted into the contralateral defect (BMP (-) group). 2, 4, 8, and 12 weeks after implantation, the defects were examined. In the BMP (+) group, newly formed bone was found in all defects from 4 weeks onward and was marked at 12 weeks. In contrast, the BMP (-) group showed no appreciable new bone formation, even at 12 weeks. Moreover, density of newly formed bone in the BMP (+) group was similar to that of the surrounding cortical bone at 12 weeks. These findings suggest that rhBMP-2/PGS is an effective bone substitute for reconstructive surgery of the dog mandible.

Absorbable Implants↗

Anterior interbody fusion of the cervical spine with coralline hydroxyapatite.

STUDY DESIGN: A nonrandomized, retrospective human study of patients requiring anterior discectomy and reconstruction from C3 to T1. The pattern of incorporation, presence or absence of disc space collapse, maintenance of correction, and clinical outcomes were considered. OBJECTIVE: To determine the efficacy of coralline hydroxyapatite as a bone replacement in anterior interbody fusions of the cervical spine used in conjunction with rigid plate fixation. SUMMARY OF THE BACKGROUND DATA: Autograft is the gold standard for anterior interbody fusion of the cervical spine. Reported complication and morbidity rates with the use of autograft are as high as 21%. Using allograft instead of autograft presents numerous problems including lower rates of fusion. Other bone substitutes such as ceramics and polymethylmethacrylate are ineffective for fusion. METHODS: Twenty-six skeletally mature patients underwent anterior decompression, stabilization, microdiscectomy, and reconstruction with Pro Osteon 200 (Interpore Cross International, Irvine, CA) coralline hydroxyapatite and AO anterior cervical locking plates. Iliac crest autograft, local bone, and allograft were not used. RESULTS: The minimum follow-up period was 2 years (average, 30 months). There was no evidence of plate breakage, screw breakage, resorption of the implant, or pseudarthrosis. Two patterns of incorporation were identified. The implant incorporated totally in 100% of the disc spaces. Average hospital stay was 1.6 days. The average decrease in pain was 75.8%. There was no evidence of nonunion. CONCLUSIONS: The use of Pro Osteon 200 with rigid anterior plating seems promising as a bone replacement in the cervical spine. The incorporation rate is exceedingly high, and the complication rate nonexistent.

Adult↗

[Experimental study on osteoinduction of coral composited artificial bone].

OBJECTIVE: To improve the osteoinduction of coral and provide a perfect bone graft substitute for clinical bone defects. METHODS: By combining coral with collagen and recombinant human bone morphogenetic protein-2(rhBMP-2), coral/collagen/rhBMP-2 composite was obtained. The composite was implanted into the back muscle pouches of mice, and coral/collagen or coral/rhBMP-2 were implanted as control. The osteoinduction of the composite was assessed by histology and image analysis system. RESULTS: The chondrocyte differentiation and matrix formation were observed in local sites after one week, lamellar bone with bone marrow were formed after 4 weeks, and coral were absorbed partially. The quantity of osteoinduction was time-related and rhBMP-2 dose-related(P < 0.01). Coral/collagen and coral/rhBMP-2 implants did not show any bone or cartilage formation. CONCLUSION: The coral/collagen/rhBMP-2 composite possesses a superior osteoinduction and will be a new type of bone substitute to be used in orthopedic and maxillofacial surgery.

Animals↗

In vivo evaluation of hydroxyapatite foams.

Hydroxyapatite (HA) is widely applied as bone graft material due to its osteoconductive potential and well-established biocompatibility. In this work, macroporous hydroxyapatite structures made through foaming of aqueous suspensions and gelcasting were tested for in vivo osteointegration. These foams are composed of a three-dimensional array of spherical pores with diameters of approximately 100-500 microm, interconnected by windows of smaller size in the range of 30-120 microm. The HA foams were implanted in the tibia of albino New Zealand rabbits and removed after a period of 8 weeks. Histological analysis revealed that the pores in the foams were partially or completely filled progressively with mature new bone tissue and osteoid after the implanted period. No immune or inflammatory reactions were detected. The high osteoconductive potential of the HA foams provides a potential structure for use as bone substitute in orthopedic, oral, and cranio-maxillofacial reconstructive surgery, and as dento-alveolar implants.

Animals↗

The effect of processing on the structural characteristics of vancomycin-loaded amorphous calcium phosphate matrices.

Calcium polyphosphate antibiotic delivery matrices were prepared using a unique processing technique involving the exposure of calcium polyphosphate pastes to high humidity for 0, 5, 24 or 48 h to induce gelling. Subsequently, samples were dried for a minimum of 24 h. The mild conditions associated with matrix fabrication readily allowed for vancomycin incorporation within an environment that did not disrupt antibiotic activity. While reproducible from a processing standpoint, the gelling and drying process did contribute to a decrease in matrix tensile strength and the formation of significant pores near the surface of the matrices. Generally, the core of the gelled matrices appeared to be denser than their non-gelled counterparts. The degree of phosphate chain lysis during the gelling and drying stages was quantified using solution 31P nuclear magnetic resonance (NMR) spectroscopy. Both NMR and Raman spectroscopy indicated that the presence of vancomycin did not appreciably alter the matrix formation process. The ability to incorporate clinically relevant levels of antibiotic within this degradable bone substitute matrix suggests the potential of this approach for creating a localized antibiotic delivery system to treat osteomyelitis infections.

Anti-Bacterial Agents↗

Gentamicin-loaded calcium carbonate materials: comparison of two drug-loading modes.

Synthetic aragonite-based porous materials were drug loaded with gentamicin sulphate, an antibiotic active on Staphylococcus aureus responsible for osteomyelitis. Drug loading was accomplished by two different ways: by integration of gentamicin in material during processing or by soaking material into gentamicin solutions. We first investigated the influence of drug loading on compressive strength of materials. Results indicate that soaked materials presented the same compressive strength than unloaded materials with the same porosity. By contrast, the integration of gentamicin during processing increased significantly the compressive strength of materials. The materials drug content before elution was a least 10 times higher when gentamicin was integrated during processing comparatively to soaked materials. The study of in vitro gentamicin release showed that for materials with gentamicin integrated during material processing, high concentrations of gentamicin were released up to 8 or 12 days, against 4 days for soaked materials. The transport coefficients calculation, for the first step of release, indicated that the rate of release was higher for materials with integrated gentamicin because of the higher gentamicin content. The porosity rate influenced the rate of release for materials positively with gentamicin integrated during processing contrary to soaked materials for which a higher porosity rate allowed a deeper penetration of gentamicin during drug loading and then a slightly slower release. Results indicate that aragonite-based material with gentamicin integrated during material processing may be used either as resorbable device for release of high concentrations of gentamicin or as biomaterial for combined therapy: bone substitution and prevention or treatment of osteomyelitis.

Anti-Bacterial Agents↗

Tailor-made tricalcium phosphate bone implant directly fabricated by a three-dimensional ink-jet printer.

Rapid prototyping (RP) is a molding technique that builds a three-dimensional (3D) model from computer-aided design (CAD) data. We fabricated new tailor-made bone implants (TIs) from alpha-tricalcium phosphate powder using an RP ink-jet printer based on computed tomography (CT) data, and evaluated their safety and efficacy. CT data of the skulls of seven beagle dogs were obtained and converted to CAD data, and bone defects were virtually made in the skull bilaterally. TIs were designed to fit the defects and were fabricated using the 3D ink-jet printer with six horizontal cylindrical holes running through the implants, designed for possible facilitation of vascular invasion and bone regeneration. As a control, hydroxyapatite implants (HIs) were cut manually from porous hydroxyapatite blocks. Then, craniectomy was performed to create real skull defects, and TIs and HIs were implanted. After implantation, CT was performed regularly, and the animals were euthanized at 24 weeks. No major side effects were observed. CT analysis showed narrowing of the cylindrical holes; bony bridging between the implants and the temporal bone was observed only for TIs. Histological analysis revealed substantial new bone formation inside the cylindrical holes in the TIs, while mainly connective tissues invaded the porous structures in HIs. Bone marrow was observed only in TIs. Osteoclasts were seen to resorb regenerated bone from inside the cylindrical holes and to invade and probably resorb the TIs. These data suggest that TIs are a safe and effective bone substitute, possessing osteoconductivity comparable with that of HIs.

Animals↗

Influence of stability and mechanical properties of a spinal fixation device on production of wear debris particles in vivo.

A prospective and quantitative animal study was performed to evaluate the production of wear particles from a spinal fixation device, and to test the hypothesis that the concentration of wear debris particles adjacent to spinal fixation hardware is correlated with the stiffness of the spinal fusion construct and local bone formation at the fusion site. An established canine segmental spinal fusion model with three interfacet fusions was used in this study. Several bone substitute materials were grafted to the area of the interfacet fusion. Internal fixation was performed on both sides of the spinous processes at each site using a stainless steel plate system in 19 dogs. After 12 weeks, spinal segments were excised, then 3-dimensional computerized tomography was used to measure bone volume and bone area of the individual fusion sites. The stiffness of each segment was tested using a servohydraulic materials testing machine. Biopsies were obtained from the soft tissues immediately around the plate system, and wear particles were collected and characterized using an electrical resistance particle analyzer, light and scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX). Biopsies from para-spinal tissue from adjacent, unoperated spinal levels served as negative controls. Histologically, 24 of 57 specimens (42.1%) showed only fibrous tissue with no recognizable macrophages, inflammation, or debris. Fourteen of 57 specimens (24.6%), however, contained many particles that were composed of Fe, Cr, and Ni, corresponding to elements found in the fixation hardware. Another 19 specimens showed only occasional particles. The mean concentration of particles from the tissue around the plate system was 2.8 x 10(9) per gram dry tissue weight, compared to 0.5 x 10(9) particles per gram for controls (p < 0.05). Statistical analyses showed significant inverse correlation between the log particle number and stiffness (r = -0.41, p < 0.01), bone volume (r = -0.28, p < 0.05), and bone area (r = -0.34, p < 0. 05) of the corresponding segments. The concentration of particles in the tissue showed a significant inverse correlation with stiffness, bone volume, and bone area of the fusion constructs.

Animals↗