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PubMed2002

Recombinant human bone morphogenetic protein-2 promotes osteogenesis within atelopeptide type I collagen solution by combination with rat cultured marrow cells.

We evaluated the combination effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and cultured rat bone marrow mesenchymal stem cells (MSCs) in atelopeptide type I collagen (AC) solution on osteogenesis in a diffusion chamber (DC) to develop a bone substitute having consistent osteogenic capability for clinical applications. The cultured MSCs were obtained by 10-day primary culture of fresh bone marrow cells of Fischer rats. We prepared three groups of DCs: AC solution with rhBMP-2, AC solution with cultured MSCs, and AC solution with rhBMP-2 and cultured MSCs. The prepared combined solutions were injected into DCs, which were subcutaneously implanted into the backs of syngeneic rats. DCs were harvested after 2, 4, or 8 weeks and analyzed for bone-forming capability by determining histological and osteoblastic biochemical markers. De novo bone formation was observed both inside and outside of the membrane filter of DCs in the group of AC solution with rhBMP-2 and cultured MSCs. The alkaline phosphatase activity and osteocalcin content in the group of AC solution with rhBMP-2 and cultured MSCs were significantly higher than those in the group of AC solution with cultured MSCs at any time. These findings indicate that AC aqueous solution is a useful material not only as a carrier of rhBMP-2 but also as a cell-anchorage for differentiation and proliferation of MSCs. Therefore, this study suggests that clinical repairs of bone defects are feasible using injectable AC solution with rhBMP-2 and cultured MSCs as a bone substitute.

Alkaline Phosphatase↗
PubMed2004

Maxillary sinus augmentation with a synthetic cell-binding peptide: histological and histomorphometrical results in humans.

Bone substitutes should be used when sufficient amounts of autologous bone cannot be harvested from intraoral donor sites. P-15 is a highly conserved linear peptide with a 15 amino acid sequence identical to the sequence contained in the residues 766 to 780 of the alpha-chain of type I collagen. PepGen P-15 (Dentsply Friadent, Mannheim, Germany) is a combination of the mineral component of bovine bone (Osteograf/N 300) with P-15. Bio-Oss (Geistlich, Mannheim, Germany) is a deproteinized sterilized bovine bone with 75% to 80% porosity and a crystal size of approximately 10 microm in the form of cortical granules. The purpose of the present histological and histomorphometrical study was to compare maxillary sinus augmentation procedures in humans performed with PepGen P-15 with procedures associated with Bio-Oss and autologous bone. Seven patients participated in this study (3 men and 4 women; ages between 48 and 69 years, mean of 58 years) and were categorized into 3 groups. In group 1, a mixture of 50% autologous bone from an intraoral source and 50% Bio-Oss was used. In group 2, the graft materials used were 50% Bio-Oss and 50% PepGen P-15. In group 3, 50% autologous bone and 50% PepGen P-15 were used. Group 1 histomorphometry showed that the percentage of newly formed bone was 38.7% +/- 3.2%, marrow spaces represented 45.6% +/- 5%, and residual graft particles constituted the remaining 14.4% +/- 2.1%. Group 2 histomorphometry showed that newly formed bone represented 36.7% +/- 3.3%, marrow spaces represented 39.7% +/- 3.4%, and residual graft particles represented 19.6% +/- 2.1%. In group 3, newly formed bone represented 32.2% +/- 3.2%, marrow spaces represented 38% +/- 2.5%, and residual graft particles represented 28.8% +/- 1.1%. Non-statistically significant differences were found in the percentage of newly formed bone in the different groups (P = .360). Statistically significant differences were found in the percentage of residual graft materials among the different groups (group 1 vs groups 2 and 3) (P = .0001). These data demonstrate that the use of bone-replacement materials, without the addition of autologous bone, could be an alternative in sinus augmentation procedures. Such treatment would increase patient satisfaction, decrease surgical complications, and save the clinician substantial operating time.

Aged↗
PubMed1997

In vivo study of a calcium phosphate cement consisting of alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide.

Prehardened calcium phosphate cement consisting of alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate monoxide (TeCP) was implanted in rabbit mandibles and back muscles, and studied histologically and microradiographically. In the mandibles, new bone formation occurred around the implants and increased in quantity the longer the implant period lasted. Histology, microradiography and scanning electron microscopy (SEM) demonstrated direct contact of bone and cement. Bone response to this cement was essentially the same as to hydroxyapatite (HA) ceramics, known as a biocompatible bone substitute. Material resorption was recognized, which increased with the implant period and was greater in the surface bound by soft tissue than the surface bound by bone tissue. In the back muscles, however, no calcified tissue formation occurred. Resorption proved to be faster than in the case of the mandible implants. It was concluded that the cement, in prehardened form, has good biocompatibility and is a promising material as a bone substitute.

Animals↗
PubMedDate not supplied

Comparison of in vitro mineralization by murine embryonic and adult stem cells cultured in an osteogenic medium.

Nearly half a million bone-grafting procedures occurred in the United States in the year 2000. Tissue-engineered bone substitutes may mitigate difficulties associated with current grafting options. Embryonic stem cells (ESCs) could be a potential cell source for bone substitutes; however, direct comparisons between ESCs and other cell sources are lacking. Here we provide a direct, long-term, in vitro comparison of mineralization processes in adult, marrow-derived, mesenchymal stem cells (MSCs) and ESCs from the 129/Sv+c/+p mouse strain. MSCs were observed to grow at a slower rate than ESCs. MSCs expressed seven times more alkaline phosphatase (AP) per cell than did ESCs and immediately showed type I collagen and osteocalcin production. ESCs also produced type I collagen and osteocalcin, but production was delayed. Mineral deposition by ESCs was nearly 50 times higher than by MSCs. Spectroscopic analysis showed the calcium-to-phosphorus ratio (Ca:P) of the ESC mineral (1.26:1) to be significantly higher than that of the MSCs (0.29:1), but still 25% lower than hydroxyapatite (1.67:1). Addition of basic fibroblast growth factor significantly inhibited AP expression, mineral deposition, and Ca:P ratios in MSCs and had little effect on ESCs. These functional characteristics may assist with cell selection for purposes of bone tissue engineering.

Aging↗
PubMedDate not supplied

Carbonated apatite and hydroxyapatite in craniofacial reconstruction.

Alloplastic biomaterials have revolutionalized craniofacial reconstruction. Commercially available bone substitute cements allow easy contouring and application, as well as avoidance of postoperative donor site complications. Hydroxyapatite and carbonated apatite are commercially available biomaterials currently being used as moldable bone substitutes in craniofacial reconstruction. This study presents 35 patients with 46 sites of reconstruction using hydroxyapatite or carbonated apatite. The characteristics, effectiveness, advantages, and limitations of each biomaterial are discussed.

Adolescent↗
PubMed1997

[Experimental study on bone formation in a denser coral used for repairing cortical defects in dogs].

The present study was designed to investigate a coral skeleton, Favites, which was originated from the reef builders in Hainan island, as a bone substitute. The coral Favites, like porites, is composed of anagonite (CaCO3), but contains less volume of porosity, higher strength and denser construction than Porites. After implanted into cortical bone defects in mandibles and femurs of dogs, skeleton fragment of coral Favites demonstrated good biocompatibility and biodegradability. A resorption of the implant and a simultaneous apposition of new bone was observed. Coral Favites was totally replaced by newly formed bone after a period of time from 6-8 months. Compared to Porites, Favites has a lower rate of resorption and therefore the defects of host bone are repaired completely without any lost of bone volume. The results showed that coral Favites may be used as a bone substitute for the segmental defects of mandibles.

Animals↗
PubMed1997

Particulate bioglass compared with hydroxyapatite as a bone graft substitute.

Bioactive ceramics, notably hydroxyapatite, have been used clinically in various situations in which bone augmentation and restoration are required. Particulate material has been used either alone or in conjunction with freeze dried or autologous bone, with variable clinical success. In this study a bioactive glass, 45S5 Bioglass, has been compared with hydroxyapatite in an animal model to discover whether the 2 major disadvantages of hydroxyapatite may be overcome. These are the difficulty of placing and retaining the particulate in the defect and the length of time needed before full bony restoration is achieved. Bioglass is shown to be easy to manipulate and hemostatic and allows full restoration of bone in 2 weeks, rather than the 12 weeks needed for the particulate hydroxyapatite to produce a comparable response. The Bioglass particulate is used up in the process, and any problems that may be associated with the production of a composite of bone and biomaterial are avoided in the fully restored bone. In any procedure that requires bony augmentation, this rapid response to Bioglass is expected to provide a clinical advantage.

Animals↗
PubMed2006

The copolymer of epsilon-caprolactone-lactide and tricalcium phosphate does not enhance bone growth in mandibular defect of sheep.

In the field of craniomaxillofacial and orthopaedic surgery there is a constant need for bone or bone substitute. At the present, the most effective way to enhance bone healing clinically is to use autogenous bone grafts. The problems associated with the use of these autografts are donor site morbidity, limited supply and need for a second operative site. Currently there are several different synthetic products commercially available in the market; nevertheless, none of them is ideal for filling bone defects. Therefore, search for new synthetic materials for bone replacement is necessary. A mixture of tricalcium phosphate (TCP) and epsilon-caprolactone-lactide copolymer P(epsilon -CL/DL-LA) was prepared and implanted in critical size mandibular bone defects in twelve sheep. Contralateral side was used as a control. Follow-up times for histological and radiological studies were 9, 14, 24 and 52 weeks. We found that the implanted material did not enhance bone formation compared to control site. We also confirmed that defect size was of critical size, since there was no complete healing of the control site either. The results do not encourage us to continue our studies with the mixture of TCP and P(epsilon-CL/DL-LA) as a filling material for bone defects. Therefore the search for the ideal material is still ongoing.

Animals↗
PubMed1989

[Biodegradable ceramic as a bone graft substitute followed by orthodontic tooth movement].

This study was performed to evaluate the histological changes during remodelling of autogenous PMCB (particulate marrow and cancellous bone) and TCPC (beta-tricalcium phosphate ceramic) when transplanted into the jaw bone defects, and also to investigate the possibility of orthodontic tooth movement on them. Twenty dogs were used in this study. Following extraction of the upper 2nd and 3rd incisors, or only the 2nd incisor, maxillary alveolar bones were resected bilaterally. Autogenous PMCB obtained from the ilium and TCPC (Synthograft, Miter, Inc. U.S.A.) were grafted in each resected area. Nine dogs were sacrificed without applying the orthodontic force, whereas the rest of dogs were sacrificed after applying orthodontic force. Sectional arch wire with open coil spring was placed between the upper 1st incisors for tooth movement. Applications of orthodontic force were started anywhere from the 2nd to the 8th week following the grafting and continued for different experimental periods. Sections of maxillary bone including the grafted areas were prepared for light microscopy. It was observed that Synthograft area showed better organization than the bone graft area initially. However, later around the 8th week, both graft materials were well organized. The Synthograft was well accepted by the host tissue. The Synthograft filled area reconstructed the bony architecture more similar to the alveolar bone than the bone graft area. In addition, the radiological findings also showed orthodontic tooth movement through the PMCB and the Synthograft areas. Capability of orthodontic tooth movement at the Synthograft areas without any undue result is of significant clinical value. Thus in view of above points in conclusion it is suggested that, TCPC is a competent substitute for PMCB in filling up alveolar bone defects, even, in cases where orthodontic tooth movement is desirable.

Alveolar Process↗
PubMed2006

First histological observations on the incorporation of a novel nanocrystalline hydroxyapatite paste OSTIM in human cancellous bone.

BACKGROUND: A commercially available nanocrystalline hydroxyapatite paste Ostim has been reported in few recent studies to surpass other synthetic bone substitutes with respect to the observed clinical results. However, the integration of this implantable material has been histologically evaluated only in animal experimental models up to now. This study aimed to evaluate the tissue incorporation of Ostim in human cancellous bone after reconstructive bone surgery for trauma. METHODS: Biopsy specimens from 6 adult patients with a total of 7 tibial, calcaneal or distal radial fractures were obtained at the time of osteosynthesis removal. The median interval from initial operation to tissue sampling was 13 (range 3-15) months. Samples were stained with Masson-Goldner, von Kossa, and toluidine blue. Osteoid volume, trabecular width and bone volume, and cortical porosity were analyzed. Samples were immunolabeled with antibodies against CD68, CD56 and human prolyl 4-hydroxylase to detect macrophages, osteoblasts, and fibroblasts, respectively. TRAP stainings were used to identify osteoclasts. RESULTS: Histomorphometric data indicated good regeneration with normal bone turnover: mean osteoid volume was 1.93% of the trabecular bone mass, trabecular bone volume--28.4%, trabecular width--225.12 microm, and porosity index--2.6%. Cortical and spongious bone tissue were well structured. Neither inflammatory reaction, nor osteofibrosis or osteonecrosis were observed. The implanted material was widely absorbed. CONCLUSION: The studied nanocrystalline hydroxyapatite paste showed good tissue incorporation. It is highly biocompatible and appears to be a suitable bone substitute for juxtaarticular comminuted fractures in combination with a stable screw-plate osteosynthesis.

Adult↗
PubMed1998

Evaluation of filling materials in membrane--protected bone defects. A comparative histomorphometric study in the mandible of miniature pigs.

In recent years, bone grafts and bone substitutes have been increasingly utilized underneath barrier membranes to optimize the treatment outcome of bone reconstructive therapy for defects in the alveolar process. In the present study, 4 different filling materials were evaluated in bone defects of similar dimensions in the mandible of miniature pigs. Blood clots and autografts were used as controls. The defects were covered with barrier membranes and allowed to heal for 4, 12 or 24 weeks. Histologic examination demonstrated that bone repair progressed through a programmed sequence of maturation steps closely resembling the pattern of bone development and growth regardless of whether bone grafts or substitutes were present or not. Histomorphometric analysis showed that autologous bone grafts (autografts) had the best osteoconductive properties during the initial healing period, with 39% of newly formed bone inside the membrane-covered defects at 4 weeks of healing. In addition, 87% of the graft surfaces were already covered by bone at this time. Both values were significantly higher for autografts than for the 4 alternative bone fillers (P < or = 0.05). At 12 weeks, these differences were no longer apparent, with all 5 filling materials showing similar values. Among the tested bone substitutes, tricalcium phosphate (TCP) showed a significantly higher percentage of bone fill at 24 weeks of healing. It can be concluded that sites filled with autografts clearly demonstrated the best results underneath barrier membranes in the early phase of healing. As far as degradation and substitution are concerned, TCP showed the most promising results. This filler, however, needs to be tested further in a more demanding animal model. Less favorable results were obtained for coral-derived hydroxyapatite granules and for demineralized freeze-dried bone allografts.

Alveolar Bone Loss↗
PubMedDate not supplied

Bioactive glass-ceramics in facial skeleton contouring.

The removal of certain facial-bone defects is a prerequisite to restoration of function, stability, and appearance. Synthetic bone substitutes are beneficial in cases where other operative techniques would be an unacceptable burden for a patient. Satisfactory results can be achieved in one surgical intervention with low costs and low demand on technical equipment. Osteoconductive, biocompatible, non-resorbable glass-ceramic implants based on oxyfluoroapatite and wollastonite permit osteointegration--a direct physical and chemical bond between live bone tissue and the implant without formation of a fibrous capsule. They display better stress durability in simulated body fluid than hydroxyapatite implants do. This material was used for facial skeletal framework, contour restoration in 44 cases under conditions where other solutions were doubtful. Patients were observed for 24.8 months. Immediate healing occurred without any adverse reaction. The main problem was extrusion, observed in 20.45% cases over a 2-3 month period after the implantation. All cases, with one exception, were solved with a satisfactory final result by reoperation, implant size reduction, and increased soft tissue cover. This approach was found to be a suitable technique, especially for patients exhausted by prior incompetent treatment but still dissatisfied with their appearance. Successful reconstruction with a bone substitute may remarkably increase quality of life for affected persons and, at the same time, reduce surgery-related time and costs.

Adolescent↗
PubMed2006

Effects of surgical errors on small fragment screw fixation.

OBJECTIVES: The purpose of this study is to determine the effects of technical errors that occur during the application of small fragment screw fixation and to assess which screw holes can be salvaged. INTERVENTION: Testing of screw pullout from a bone substitute model on a universal testing instrument (Instron Corp., Canton, MA). OUTCOME MEASUREMENTS: Testing was performed on 9 sets of 12 small fragment screws applied to a bone substitute model using the instruments available in a small fragment set (Synthes, Paoli, Pa). In the first 2 sets, 3.5-mm cortical screws and 4.0-mm cancellous screws were placed using the proper instrumentation according to recommended AO/ASIF techniques. The other 7 sets were inserted using "incorrect" methods: a single step was altered intentionally to assess its influence on fixation strength. The third set of screws included 3.5-mm cortical screws placed after drilling the pilot hole with a 3.5-mm drill. For the fourth set, the 2.5-mm drill was used, but the hole was tapped using the 4.0-mm cancellous tap before insertion of a 3.5-mm cortical screw. In set five, 4.0-mm cancellous screws were placed after tapping the hole with a 3.5-mm cortical tap. Set 6 included cancellous screws placed without tapping. The seventh set included 3.5-mm cortical screws that were placed according to recommended methods, and then removed and replaced into the screw hole. Set number 8 included 3.5-mm cortical screws, which were inserted correctly and then stripped by overtightening. The ninth set included 3.5-mm cortical screws that were stripped as those in set 8; the stripped screws were removed, the holes were packed with bone material, and the screws were replaced. All screws were inserted to a thread depth of 32 mm. RESULTS: Drilling a 3.5-mm pilot hole for a 3.5-mm cortical screw and "stripping" the screw by overtightening resulted in 76% and 82% less pullout strength, respectively, than when the proper technique was used (P<0.01). Use of the wrong tap before placement of a 3.5-mm cortical or 4.0-mm cancellous screw decreased pullout strength by 12% and 11%, respectively (P<0.01). Exchanging screws of similar geometry had no significant effect on screw pullout strength (P>0.1). Inserting a 4.0-mm cancellous screw without tapping actually increased pullout strength by 4% (P<0.01). CONCLUSIONS: Alterations from recommended techniques for the placement of orthopedic screws had varying effects on screw fixation, as assessed by the pullout strength. Clinically, these findings indicate that, in some cases, a screw hole that was not initially placed according to the optimal technique may be salvaged. Finally, the authors recommend that careful vigilance be maintained at all times in surgery and that fixation be applied according to sound principles in an effort to avoid some of these problems.

Bone Screws↗
PubMed2005

The future of bone healing.

With more than 5.5 million fractures and 1 million bone repair surgeries annually, bone graft plays a significant role in aiding fracture repair. In the United States alone, surgeons perform an estimated 500,000 to 600,000 bone grafting procedures annually. With the advent of possibilities from bone substitutes, growth factors, and stem cell research, the potential for enhancing bone healing is vast. This article attempts to survey current trends and to highlight upcoming techniques in the future of bone healing.

Bone Substitutes↗
PubMed2003

Angiogenesis after sintered bone implantation in rat parietal bone.

We studied the effect of bone substitutes on revascularization and the restart of blood supply after sintered bone implantation in comparison with synthetic hydroxyapatite implantation and fresh autogenous bone transplantation (control) in rat parietal bones. Methods for the study included the microvascular corrosion cast method and immunohistochemical techniques were also used. The revascularization of the control group was the same as that for usual wound healing in the observations of the microvascular corrosion casts. The sintered bone implantation group was quite similar to that of the control group. In the synthetic hydroxyapatite group, immature newly-formed blood vessels existed even on the 21st day after implantation and the physiological process of angiogenesis was interrupted. Immunohistochemically, vascular endothelial growth factor (VEGF), which activates angiogenesis, appeared at the early stages of both the control group and the sintered bone implantation group. VEGF reduced parallel with the appearance of the transforming growth factor factor-beta-1 (TGF-beta-1), which obstructs angiogenesis, and the angiogenesis passed gradually into the mature stage. In the hydroxyapatite implantation group, TGF-beta-1 appeared at the early stage of the implants. The appearance of VEGF lagged and it existed around the pores of hydroxyapatite even on the 21st day of the implantation. Proliferation and wandering of endothelial cells continued without any maturing of the vessels. These findings suggest that the structure and the components of the implant material affect angiogenesis after implantation as well as new bone formation.

Animals↗
PubMed2004

The functional expression of human bone-derived cells grown on rapidly resorbable calcium phosphate ceramics.

The use of biodegradable bone substitutes is advantageous for alveolar ridge augmentation, since it avoids second-site surgery for autograft harvesting. This study examines the effect of novel, rapidly resorbable calcium phosphates on the expression of bone-related genes and proteins by human bone-derived cells (HBDC) and compares this behavior to that of tricalciumphosphate (TCP). Test materials were alpha-TCP, and four materials which were created from beta-Rhenanite and its derivatives: R1-beta-Rhenanite (CaNaPO(4)); R1/M2 composed of CaNaPO(4) and MgNaPO(4); R1+SiO(2) composed of CaNaPO(4) and 9% SiO(2) (wt%); and R17-Ca(2)KNa(PO(4))(2). HBDC were grown on the substrata for 3, 5, 7, 14 and 21 days, counted and probed for various mRNAs and proteins (Type I collagen, osteocalcin, osteopontin, osteonectin, alkaline phosphatase and bone sialoprotein). All substrata supported continuous cellular growth for 21 days. At day 21, surfaces of R1+SiO(2) and R17 had the highest number of HBDC. At 14 and 21 days, cells on R1 and on R1+SiO(2) displayed significantly enhanced expression of all osteogenic proteins. Since all novel calcium phosphates supported cellular proliferation together with expression of bone-related proteins at least as much as TCP, these ceramics can be regarded as potential bone substitutes. R1 and R1+SiO(2) had the most effect on osteoblastic differentiation, thus suggesting that these materials may possess a higher potency to enhance osteogenesis than TCP.

Bone Substitutes↗
PubMed1998

Biological effects and cytotoxicity of the composite composed by tricalcium phosphate and glutaraldehyde cross-linked gelatin.

The purpose of this study was to prepare and evaluate the feasibility and cytocompatibility of a composite (GTG) as a large defect bone substitute. The composite is combined with tricalcium phosphate ceramic particles and glutaraldehyde cross-linked gelatin. Gelatin had been reported as an adhesive and biocompatible binder that could accelerate the recovery of damaged soft tissue, but the effects of gelatin when acting on the bone tissue is not clear. Thus, it is necessary to determine if the substances released from the GTG composite can facilitate the growth of bone cells. The substances released from the GTG composites after being soaked in deionized distilled water were analyzed by gas chromatography (GC), ultraviolet and visible absorption spectroscopy (UV-VIS), and inductive-coupled plasma-atomic emission spectrometry (ICP-AES). The cytotoxicity of the GTG composites was assessed by coculture of rat osteoblasts in vitro. Extracts were obtained by soaking the GTG composites in deionized distilled water for 1, 2, 4, 7, 14, 28 and 42 d. The extract mixed with complete medium in a ratio of 1:1 was added into the cell culture wells containing 1 x 10(4) cells ml(-1) osteoblasts. After culturing for 2 days, the cells attached to the surface of wells were trypsinized and the number calculated by the Neubauer counting-chamber under the optical microscope. Finally, three samples in each GTG group were examined by scanning electron microscopy (SEM) to observe the morphology of the osteoblasts attached to the surfaces of GTG composites. The examinations of osteoblasts cocultured with the developed GTG composites were used to decide the ideal concentration of glutaraldehyde as a cross-linking agent. The results of extracts cocultured with osteoblasts showed that the extracts obtained from the 2, 4 and 8% glutaraldehyde cross-linked GTG composites would inhibit the growth of osteoblasts in the first 4 soaking days. During the 4-7 days soaking, the cell numbers quickly increased with the soaking time, thereafter, the cell numbers almost reached a constant value. In the analyses of substances released from the GTG composites, it was found that the gelatin and calcium were gradually released from the GTG composites, which were supposed to be nutritious for the growth of the osteoblast. The results of osteoblasts cocultured with the GTG composites showed that the concentration of glutaraldehyde used as a cross-linking agent should be lower than 8%. Compared to the GTF (composite combined with tricalcium phosphate ceramic particles and formaldehyde cross-linked gelatin), GTG composites were much suitable for a large defect bone substitute in the near future.

Animals↗