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PubMedDate not supplied

Investigation of early bone formation using resorbable bioactive glass in the rat mandible.

Recent advances in biomaterial technology have made alloplastic bone substitutes more predictable when used with the proper clinical methodology in carefully selected patients. In this animal study, early bone formation using a novel resorbable bioactive glass in the repair of surgically created bony defects in the rat mandible was investigated. Biopsies taken from the implanted sites after 1, 2, 3, 4, 8, and 16 weeks were examined histologically by means of standard cell-staining techniques. In addition, an electron probe microanalyzer was used to determine the presence and distribution of specific elements in samples taken after 16 weeks. Results indicated the early stage of osteoconductive bone growth after approximately 4 weeks. After 16 weeks, electron probe micro-analyzer scans indicated the formation of a calcium-phosphate shell formed in situ and the resorption of silica to background levels.

Absorbable Implants↗
PubMed1996

Osteoinductive potential of freeze-dried, biodegradable, poly (glycolic acid-co-lactic acid) disks incorporated with bone morphogenetic protein in skull defects of rats.

Biodegradable, porous, polymer implant disks with an osteoinductive potential were prepared by a freeze-drying technique by incorporating bovine bone morphogenetic protein (BMP) in poly (glycolic acid-co-lactic acid) (PGLA). The PGLA disks with and without BMP were implanted in rat skull defects, and the defect sites were studied radiographically and histologically for 2 and 4 weeks after implantation. A quantitative radiographic analysis showed significantly thicker radiopacity for the disks with BMP than those without BMP (P < 0.01). After 2 weeks, chondrogenesis and new bone formation were observed on the BMP-incorporated disks. After 4 weeks, PGLA was completely replaced by new bone in the defects with implantation of the BMP-incorporated disks, whereas the defects implanted with PGLA alone were filled with fibrous connective tissue. The results suggest that BMP-incorporated PGLA is an ideal bone substitute with osteoinductive potential.

Animals↗
PubMed2004

Biocompatibility and biodegradation of a bone composite containing tricalcium phosphate and genipin crosslinked gelatin.

A biodegradable composite (GGT) containing tricalcium phosphate ceramic particles and genipin crosslinked gelatin was developed for use as a bone substitute. The objective of this study was to assess the biocompatibility and the osteoconductivity of the GGT composite on new bone formation in vitro. Additionally, biodegradation and biocompatibility of the GGT composite in animals were investigated. Results of the GGT composites cocultured with osteoblasts showed that the concentration of genipin used as a crosslinking agent should be <0.5 wt % to avoid cytotoxicity. For in vivo degradation studies, we found that when the concentration of genipin in the composite <0.5 wt % was not enough to fully crosslink the gelatin, it results in a rapid degradation of the gelatin-genipin mixture. However, we also found that the foreign body capsule surrounding the GGT composite containing 1.0 wt % of the genipin was much thicker than that in the other three groups, that is, the composites containing 0.05, 0.1, and 0.5 wt % of the genipin. We therefore concluded that the ideal concentration of genipin used in the GGT was 0.5 wt %. Finally, we examined the organ culture units, which were maintained in cultured medium for 5 weeks. Morphology of tissue was observed and the quantitative evaluation of the regenerated bone was determined. We found that the GGT composites containing 0.5 wt % of the genipin had an excellent biocompatibility and could produce osteoconduction for the regenerating bone tissues.

Animals↗
PubMed1995

Biomaterials in orthopaedic surgery: effects of different hydroxyapatites and demineralized bone matrix on proliferation rate and bone matrix synthesis by human osteoblasts.

The effects of different biomaterials, used in orthopaedic surgery for bone substitution and/or prosthesis coating to improve fixation and durability of prosthetic implants, have been studied in vitro on cell growth and bone matrix synthesis by human osteoblasts. The materials were a bovine collagen matrix (Osteovit, B. Braun Melsungen AG, Melsungen, Germany) and two hydroxyapatite (Ceros 80, Robert Mathys Co, Instrumentenfabrik Bettlach, Germany and Ostilit, Howmedica International, Staines House, UK). Cell proliferation and bone matrix synthesis were assessed by incorporation of [3H]thymidine and [3H]proline, respectively. Cell viability in the presence of the materials was also morphologically controlled using phase-contrast microscopy. Exposure to Osteovit caused increased proliferation of human osteoblasts, whereas both Ostilit and Ceros 80 induced a decreased cell growth. Osteoblast bone matrix synthesis was increased by all the materials tested.

Biocompatible Materials↗
PubMed2006

Chemical-physical characterization and in vitro preliminary biological assessment of hyaluronic acid benzyl ester-hydroxyapatite composite.

HYAFF11 is a biocompatible, biodegradable benzyl ester of hyaluronic acid. However, in order to use it for orthopedic application, its mechanical performance needs to be improved. In this study, a novel composite based on HYAFF11 polymer matrix reinforced with hydroxylapatite (HA) has been developed. Its advantage is having a similar component of the mineral phase of bone resulting in favorable osteoconductive properties. The present study has examined the compressive mechanical and surface chemical-physical properties of the novel HYAFF11-HA composite. Preliminary biological investigations, including pH and cytotoxicity studies of the material extracts, have also been performed using an in vitro primary human osteoblast-like cell model. Moreover, protein, especially fibronectin adsorption has been investigated following incubation in culture medium and human plasma. The results show a grainy surface topography composed mainly of C, P, and Ca, with a Ca/P atomic ratio indicating HA on the composite surface. Mechanical analysis shows an improvement of the compressive properties of HYAFF11 matrix, both in the dry and swollen states, with values in the range of that of spongy bone. No cytotoxic effects and no inhibition of cell proliferation have been observed in the presence of the material extracts with pH values within acceptable ranges for cell vitality. Protein studies reveal a similar pattern, but a higher amount of fibronectin following incubation in human plasma when compared with culture medium. The results show that the novel HYAFF11-HA composite shows a great potential for application in orthopedic fields, especially as vertebral trabecular bone substitute.

Biocompatible Materials↗
PubMed2006

Surface chemistry and biological responses to synthetic octacalcium phosphate.

Octacalcium phosphate (OCP) has been suggested as a precursor of biological apatite in bone, dentin, and cementum because its existence explains the nonstoichiometry of apatite crystals in their compositions. Synthetic inorganic calcium phosphate compounds have been used clinically to fill bone defects, and sintered hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP), bone substitute materials, are known to be osteoconductive, with beta-TCP also being bioresorbable. Nonsintered synthetic OCP has been shown to enhance bone regeneration accompanied by conversion into hydrolyzed apatitic products in situ and biodegradation. The surfaces of the OCP implant and the converted apatite seem to be continuously exposed to biological constituents, such as extracellular matrices, inorganic biominerals, and cellular components. This article reviews the surface reaction of OCP implants and the biological responses, such as experimentally stimulated bone formation on synthetic OCP, the mechanism of OCP hydrolysis into apatite, and the adsorption of biomolecules onto OCP and the converted apatite, of particular interest in reactive bone induction with synthetic OCP implants.

Adsorption↗
PubMed2001

Bovine bone implant with bovine bone morphogenetic protein in healing a canine ulnar defect.

Xenograft is considered an alternative material for bone transplantation, but its bone healing capacity is inferior compared to that of autografts and allografts. Here, we tested whether bone morphogenetic protein (BMP) addition enhances the suitability of demineralized xenogeneic bovine bone for bone grafting in dogs, and whether xenogeneic bone is a suitable carrier material for BMPs. The capacity of demineralized bovine bone implants, with and without native partially purified bovine BMP, to heal a 2-cm ulnar defect was determined in six dogs over a follow-up time of 20 weeks. No instances of bone union were seen, but there was slightly more bone formation in the xenografts with BMP, though the difference was not statistically significant. The ulnas treated with an implant with BMP were also mechanically stronger, but the difference was not significant. Computed tomography scans showed no differences in the implant area in bone density, bone mineral content, or bone cross-sectional area. It is concluded that native, partially purified BMP does not sufficiently improve the suitability of bovine demineralized xenografts as a bone substitute material for dog. Demineralized xenogeneic bone does not seem to be a feasible carrier material for BMP.

Animals↗
PubMed2005

Bone regeneration in the rat mandible with bone morphogenetic protein-2: a comparison of two carriers.

OBJECTIVE: To compare mandibular bone regeneration with bone morphogenetic protein-2 (BMP-2) delivered with two carriers: a hyaluronic acid polymer (HY), and a collagen carrier complexed with calcium hydroxyapatite and tricalcium phosphate (collagen/HA/TCP). STUDY DESIGN: Defects were created in the bilateral mandibular bodies of 16 Sprague-Dawley rats. The defects were filled with the HY carrier, the HY carrier loaded with BMP-2, the collagen/HA/TCP carrier, or the collagen/HA/TCP carrier loaded with BMP-2. Animals were euthanatized after 6 weeks, and the hemi-mandibles were analyzed histomorphologically. RESULTS: Specimens containing BMP-2 had significantly larger new bone and marrow volumes than control specimens. Specimens in the hyaluronan/BMP-2 group tended to have larger volumes of new bone and osteoid than collagen/HA/TCP/BMP-2 specimens, though these differences were not statistically significant. CONCLUSION: The HY and collagen/HA/TCP carriers had comparable efficacy for bone healing with BMP-2. SIGNIFICANCE: Bone morphogenetic proteins can be delivered with commercially available alloplasts as osteogenic bone substitutes for the repair of craniofacial bone defects. EBM RATING: B-2.

Animals↗
PubMed2003

Ex vivo gene therapy in autologous critical-size craniofacial bone regeneration.

In therapeutic bone repairs, autologous bone grafts, conventional or vascularized allografts, and biocompatible artificial bone substitutes all have their shortcomings. The bone formed from peptides [recombinant human bone morphogenetic proteins (BMPs)], demineralized bone powder, or a combination of both is small in size. Tissue engineering may be an alternative for cranial bone repair. In this study, the authors developed an animal model to test the hypothesis that replication-defective, adenovirus-mediated human BMP-2 gene transfer to bone marrow stromal cells enhances the autologous bone formation for repairing a critical-size craniofacial defect. The mesenchymal stromal cells of miniature swine were separated from the iliac crest aspirate and expanded in monolayer culture 1 month before implantation. The cultured mesenchymal stromal cells were infected with recombinant, replication-defective human adenovirus BMP-2, 7 days before implantation. Bilateral 2 x 5-cm2 cranial defects were created, leaving no osteogenic periosteum and dura behind. Mesenchymal stromal cells at 5 x 10(7)/ml were mixed with collagen type I to form mesenchymal stromal cell/polymer constructs. Mesenchymal stromal cells used for the control site were infected with adenovirus beta-Gal under the same conditions. After 6 weeks and 3 months, 10 miniature swine were euthanized and the cranium repair was examined. Near-complete repair of the critical-size cranial defect by tissue-engineered mesenchymal stromal cell/collagen type I construct was observed. The new bone formation area (in square centimeters) measured by three-dimensional computed tomography demonstrated that the improvement from 6 weeks to 3 months was significantly greater on the experimental side than on the control side (2.15 cm2 versus 0.54 cm2, p < 0.001) and significantly greater at 3 months than at 6 weeks (2.13 cm2 versus 0.52 cm2, p < 0.001). The difference between the experimental and control groups was significant at 3 months (mean difference, 2.13 cm2; p < 0.001). The maximal compressive strength of the new bone was similar to that of the normal cranial bone when evaluated by biomechanical testing (cranium bone versus tissue-engineered bone, 88.646 +/- 5.121 MPa versus 80.536 +/- 19.302 MPa; p = 0.227). Adenovirus was absent from all constructs by immunochemical staining at 6 weeks and 3 months after implantation. The successful repair of cranial defects in this experiment demonstrates the efficacy of the integration of the autologous stem cell concept, gene medicine, and polymers in producing tissue-engineered bone.

Animals↗
PubMed2006

Induction of a barrier membrane to facilitate reconstruction of massive segmental diaphyseal bone defects: an ovine model.

OBJECTIVES: To report an ovine model that can be used to evaluate the efficacy of bone substitutes for repair of segmental diaphyseal bone defects. STUDY DESIGN: Experimental study. ANIMALS: Eleven 2-year-old Pré-Alpes Sheep. METHODS: Mid-diaphyseal metatarsal bone defects (25 mm long) were stabilized by a dynamic compression plate over a polymethylmethacrylate (PMMA) cement spacer, and by external coaptation. The PMMA spacer was removed at 6 weeks by incising the encapsulating membrane. The defect remained unfilled (Group 1; n=5) or was filled with morselized autologous corticocancellous graft (Group 2; n=6), the membrane sutured closed, and external coaptation applied for 6 months, when healing was evaluated. RESULTS: Radiographic, computed tomographic, and histologic examinations at 6 months after the 2nd surgery revealed non-union in ungrafted defects whereas grafted defects showed bone healing. The induced membrane had blood vessels, CBFA1+ cells, and very few macrophages entrapped in a collagenous tissue positive for type I collagen. CONCLUSION: This ovine metatarsal defect model resulted in a critical-size defect (non-union) that healed when grafted. The PMMA-induced membrane constrained the graft, was well vascularized, and may have osteogenic properties. CLINICAL RELEVANCE: This model may be useful to evaluate new strategies in bone tissue engineering because the PMMA-induced membrane may help confine bone morphogenetic proteins, skeletal stem cells, or other agents to the defect cavity where they could be useful to enhance bone formation.

Animals↗
PubMed1991

Advances in preprosthetic surgery and implantation.

The literature during the past year reflects a decreased emphasis on the use of nonresorbable hydroxylapatite implants in preprosthetic surgery and an increase in application of resorbable, or biodegradable, bone substitutes in the form of porous bone mineral and other biodegradable materials. The use of these materials as composite grafts with autogenous particulate marrow and cancellous bone has been reported in long-range studies. The use of bone induction substances with appropriate carries materials has likewise received emphasis in developing areas of appropriate clinical application. Intraosseous titanium implants placed in deficient bone areas have involved the use of graft materials and microporous membranes. The future application of bone inductive techniques with appropriate degradable and nondegradable carrier materials and autogenous bone with microporous membranes appears to affect bone regeneration and alveolar bone maintenance.

Alveolar Bone Loss↗
PubMed1990

[Bone inductive activity of beta-tricalcium phosphate-bone morphogenetic protein complex].

For the development of new implantable biomaterials as bone substitutes in the treatment of jaw bone defects, bone morphogenetic protein (BMP) bound to porous beta-tricalcium phosphate (beta-TCP) was investigated in the present experimental study in mice. The BMP was extracted from bovine cortical bone while the beta-TCP was synthesized by a mechanochemical method. The affinity of BMP to beta-TCP was examined by means of beta-TCP column chromatography. The porous beta-TCP combined with the BMP by dialysis was implanted in the muscle pouches of mice. The beta-TCP or BMP alone was also implanted in the same places in the controls. Three weeks after the implantation a new bone formation was observed in the exterior surface of the beta-TCP/BMP complex, but not in that of the beta-TCP control. The quantity of bone induced by the beta-TCP/BMP complex was determined on the X-ray film by a computer supported image analysis system. The osteoinductive activity of the complex was higher than that of the BMP alone. The histological relationship between the beta-TCP/BMP complex and the original tissues was excellent. The result of the present study may indicate that the beta-TCP/BMP complex can be used as an osteogenetic biomaterial for the treatment of bone tissue defects.

Animals↗
PubMed1996

Guided bone regeneration for dental implants.

The application of barrier membranes to promote bone regeneration was first described by Hurley et al. (J Bone Joint Surg 1959, 41A:1243-1254) in orthopedic research. However, the clinical potential of this membrane technique was recognized in the early 1980s for periodontal regeneration. Based on promising results in periodontology, researchers started to evaluate the potential of this technique--often called guided bone regeneration (GBR)--to regenerate bone defects in the alveolar process. This review describes the current knowledge of GBR in implant dentistry. Emphasis is placed on the scientific basis of GBR and the various surgical factors necessary to achieve predictable results with GBR procedures. In addition, unanswered questions that require future research are addressed including long-term success rates of dental implants placed in combination with barrier membranes, evaluation of resorbable membranes, and use of bone substitutes or growth factors to enhance bone regeneration in membrane-protected defects.

Alveolar Bone Loss↗
PubMed1995

Ridge preservation: the new buzzword in dentistry.

The viability of Ridge Preservation as achieved by practicing Advanced Extraction Therapy (AET) and Replacement Therapy (R.T.), will impact the future practice of Dentistry. With the availability of clinically proven materials such as implants (titanium) and synthetic bone substitutes (Bioplant HTR), a practical solution exists to solve a very old clinical problem. Treatment modalities are available today making the atrophic jaw-bone a malady of the past. Imagine no more "dental cripples," and no more inadequate bone situations for implant placements. Ridge Preservation and Replacement Therapy should be practiced regularly: "when we take something out, we should put something back." Our practices will grow. Our patients will thank us.

Alveolar Bone Loss↗
PubMed2005

Synthesis and characterization of porous beta-tricalcium phosphate blocks.

Porous beta-tricalcium phosphate (beta-TCP) blocks with four different macropore sizes (pore larger than 50 microm were synthesized using "calcium phosphate emulsions", and characterized by optical, geometrical, gravimetric, and radiological methods. The reproducibility of the synthesis method was excellent. Moreover, the macropore size could be easily controlled without modifying the microporosity (pore smaller than 50 microm) or the total porosity (microporosity+macroporosity). Based on the initial composition of the blocks and their final apparent density, the microporosity, macroporosity, and the total block porosity were calculated to be close to 21%, 54%, and 75%, respectively. These values were confirmed by microcomputed tomography (microCT). The mean macropore diameters were close to 150, 260, 510 and 1220 microm, as measured optically. Consistently lower values (25% lower) were obtained by microCT, but the linear correlation between microCT and optical method was high (r(2)>0.97). The macropore size distribution calculated from microCT scans appears to be narrow and normally distributed. The very good correlation between the results of the various methods and the possibility to determine the pore size distribution suggest that microCT is an ideal tool to non-destructively characterize macroporous calcium phosphate bone substitutes.

Biocompatible Materials↗
PubMed2003

Tissue response to a newly developed calcium phosphate cement containing succinic acid and carboxymethyl-chitin.

We developed a new calcium phosphate cement containing succinic acid and carboxymethyl-chitin in the liquid component. In this study, the biocompatibility and osteoconductivity of this new cement were investigated. After mixing, cement in putty form was implanted immediately between the periosteum and parietal bone and in the subcutaneous tissues of rats. In control cement, distilled water was used instead of the liquid component. In addition to histological evaluations, analyses with X-ray diffraction and Fourier transform infrared were performed for the subcutaneously implanted cements. Histological examination showed slight inflammation around the new cement on the bone and in the subcutaneous tissue at 1 week after surgery. At 2 weeks, the cement was partially bound to the parietal bone. The extent of the surface of the new cement directly in contact with the bone increased with time, and most of the undersurface of the new cement bound to the host parietal bone by 8 weeks. Analysis by X-ray diffraction showed that the new cement in the subcutaneous tissue was transformed into hydroxyapatite by 8 weeks. These results indicate that this new calcium phosphate cement is useful as a bone substitute material.

Absorbable Implants↗
PubMed2004

The in vivo calcification capacity of a copolymer, based on methacryloyloxyethyl phosphate, does not favor osteoconduction.

Polymers can be interesting alternatives to bone grafts; they must present suitable mechanical and osteoconductive properties. Biomimetic properties may be a key factor for the recognition by bone cells. Methacryloyloxyethyl phosphate (MOEP) was found to enhance hydroxyapatite deposition. The copolymer containing MOEP and 1-vinyl-2-pyrrolidinone (50-50%) binds large amounts of calcium. Particles of the copolymer were used to fill large cranial bone defects in the rat. After a 12-week healing period, the animals were euthanized and the skulls examined by X-ray, histology, and electron microscopy (EM). The high phosphate content of the polymer conferred a marked calcium-binding capacity, and the particles were heavily calcified. They were embedded in a light fibrous stroma containing numerous capillaries and multinucleated giant cells. The osteoconductive properties were poor: only few trabeculae developed centripetally from the margins of the defects. There was no bone bonding and no osteoblast on the surface of the calcified material. Backscattered EM revealed that the degree of calcification was homogeneous in all particles. Calcium-phosphorus calcospherites were never observed. The material appeared to trap calcium but to impair nucleation because only small hydroxyapatite tablets were occasionally observed. Polyphosphated materials do not represent a suitable source of potentially usable bone substitutes.

Animals↗
PubMed2001

Development of a new calcium phosphate cement that contains sodium calcium phosphate.

A cement powder consisting of sodium calcium phosphate, Na3Ca6(PO4)5, in addition to tetracalcium phosphate and beta-tricalcium phosphate was prepared by pulverizing blocks of 4 wt% sodium-, 11 wt% carbonate-containing apatite samples that were heated at 1700 degrees C for 5 h. When mixed with 30 wt% malic acid or citric acid at a powder liquid ratio of 3:1, the cement set in 3 or 7 min at room temperature with compressive strength being around 52 or 27 MPa. In HeLa-cell cultures, the cement mixed with malic acid was less cytotoxic than the cement mixed with citric acid, which was far less cytotoxic than a commercial carboxylate cement used as a negative control, suggesting malic acid to be superior to citric acid as a liquid in this regard. Similar findings were also obtained with osteoclasts, of which culture experiments clearly suggested that the number of osteoclasts on the cement mixed with malic acid was significantly greater than that on the cement mixed with citric acid. Since osteoclastic response to substrates could be used as a maker in evaluating their bioresorbability associated with osteoclasts, the above finding may suggest that the cement that is to be mixed with malic acid would be more useful as bone substitutes.

Animals↗