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[Bone substitutes].

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Biocompatible Materials↗

A bone replaceable artificial bone substitute: morphological and physiochemical characterizations.

A composite material consisting of carbonate apatite (CAp) and type I atelocollagen (AtCol) (88/12 in wt/wt%) was designed for use as an artificial bone substitute. CAp was synthesized at 58 degrees C by a solution-precipitation method and then heated at either 980 degrees C or 1,200 degrees C. In this study, type I AtCol was purified from bovine tail skins. A CAp-AtCol mixture was prepared by centirfugation and condensed into composite rods or disks. The scanning electron-microscopic (SEM) characterization indicated that the CAp synthesized at 58 degrees C displayed a crystallinity similar to that of natural bone and had a high porosity (mean pore size: about 3-10 microns in diameter). SEM also revealed that the CAp heated at 980 degrees C was more porous than that sintered at 1,200 degrees C, and the 1,200 degrees C-heated particles were more uniformly encapsulated by the AtCol fibers than the 980 degrees C-heated ones. A Fourier transformed-infrared spectroscopic analysis showed that the bands characteristic of carbonate ions were clearly observed in the 58 degrees C-synthesized CAp. To enhance the intramolecular cross-linking between the collagen molecules, CAp-AtCol composites were irradiated by ultraviolet (UV) ray (wave length 254 nm) for 4 hours or vacuum-dried at 150 degrees C for 2 hours. Compared to the non cross-linked composites, the UV-irradiated or dehydrothermally cross-linked composites showed significantly (p < 0.05) low collagen degradation and swelling ratio. Preliminary mechanical data demonstrated that the compressive strengths of the CAp-AtCol composites were higher than the values reported for bone.

Animals↗

Platelet-derived growth factor enhancement of a mineral-collagen bone substitute.

BACKGROUND: Anorganic bovine bone-collagen matrix is commercially available for bone regeneration procedures. Platelet-derived growth factor-BB (PDGF-BB) has been demonstrated to stimulate bone formation in vivo and in vitro. It was the aim of these studies to examine 1) the interaction of this mineral-collagen matrix with PDGF-BB and 2) determine if the adsorption of PDGF-BB to the mineral-collagen matrix stimulates osteoblastic cell proliferation above that of the untreated matrix. METHODS: Measurement of PDGF-BB adsorption and release was accomplished using 125I radiolabeled growth factor. The PDGF-BB was incubated with the anorganic bovine bone-collagen matrix and the amount which adsorbed was determined. In the release studies, radiolabeled PDGF-BB was adsorbed to the matrix material, then the samples were incubated in buffer for various time periods. The amount of PDGF-BB retained on the matrix was measured and the percent of growth factor released calculated. The biological activity was tested in an in vitro assay with primary culture neonatal rat osteoblastic cells. Osteoblastic cells were cultured on bone mineral-collagen matrix with known amounts of adsorbed PDGF-BB. Proliferation of the cells was assessed by 3H-thymidine incorporation and cell attachment measured by prelabeling cells with 3H-leucine. RESULTS: PDGF-BB adsorbed to the mineralized-collagen matrix material in a rapid, concentration-dependent fashion. The growth factor was slowly released from the matrix such that approximately 30% of the adsorbed protein was liberated over 10 days. PDGF-BB treated mineralized-collagen matrix displayed significantly (P < 0.05, ANOVA) enhanced proliferation of cultured osteoblastic cells compared to the mineralized-collagen matrix alone. CONCLUSIONS: These results suggest that PDGF-BB is rapidly adsorbed then slowly released from the anorganic bovine bone-collagen matrix. PDGF-BB adsorbed to this material is able to stimulate proliferation of the attached osteoblastic cells. These data suggest that it may be clinically feasible to adsorb PDGF to this bone-collagen matrix and that this combination of bone growth factor and mineral-collagen matrix has the potential for clinical applications.

Adsorption↗

Vascularization of tricalcium phosphate, an artificial bone substitute: preliminary observations.

Tricalcium phosphate (TCP), a biodegradable artificial bone substitute, was used to study the following questions: i) can TCP be vascularized; ii) do ectopically placed implants have osteoinductive capacity; and iii) does vascularization affect implant resorption? Implants were placed in dogs in several areas: i) subcutaneous controls; ii) wrapped with latissimus dorsi muscle; iii) wrapped in omentum; iv) saphenous and thoracodorsal av pedicles threaded through implant. Prior to harvest, animals were given tetracycline and implants were harvested at 3, 6, and 9 weeks. Microfil was injected prior to sacrifice and specimens were xeroradiographed. Histology and computerized axial tomography were obtained. From this study, we conclude that 1) TCP can be vascularized; 2) the most effective method of vascularization was by an AV pedicle threaded through the implant; 3) vascularized implants did not have osteoinductive properties per se, and 4) in the time observed no difference in implant resorption was demonstrated between the test groups.

Animals↗

A bone substitute composed of polymethylmethacrylate and alpha-tricalcium phosphate: results in terms of osteoblast function and bone tissue formation.

The biological properties of a composite polymeric matrix (PMMA + alpha-TCP) made of polymethylmethacrylate (PMMA) and alfa-tricalciumphosphate (alpha-TCP) was tested by means of in vitro and in vivo investigations. PMMA was used as a comparative material. Osteoblast cultures (MG 63) demonstrated that PMMA + alpha-TCP significantly and positively affected osteoblast viability, synthetic activity and interleukin-6 level as compared to PMMA. At 12 weeks, the PMMA + alpha-TCP implants in rabbit bone successfully osteointegrated in trabecular and cortical tissue (affinity index: 57.14+/-8.84% and 68.31+/-6.18%, respectively). The newly formed bone after tetracycline labelling was histologically observed inside PMMA + alpha-TCP porosity. The microhardness test at the bone-PMMA + alpha-TCP interface showed a significantly higher rate of newly formed bone mineralization compared with PMMA (+83.5% and +58.5%, respectively), but differences still existed between newly formed and pre-existing normal bone. It is herein hypothesized that the present positive results may be ascribed to the porous macroarchitecture of PMMA + alpha-TCP and the presence of the bioactive ceramic material that could have a synergic effect and be responsible for the improvement of (a) the material colonization by bone cells, (b) osteoblast activity, (c) osteoinduction and osteoconduction processes, (d) bone remodelling.

Bone Cements↗

Fabrication and evaluation of a new composite composed of tricalcium phosphate, gelatin and chi-li-saan as a bone substitute.

The purpose of this study was to prepare and evaluate the feasibility and biocompatibility of a new composite as a bone substitute. The new composite (GTGC) was mainly composed of tricalcium phosphate ceramics and gelatin to which chi-li-saan, a Chinese medicinal remedy was added. The GTGC composite was manually packed into cylindrical Teflon molds, dried overnight in an oven and sterilized by gamma-ray prior to use. Mature New Zealand rabbits, weighting 3-3.5 kg, underwent full-thickness excision of the parietal bone. In the experimental group, bone defects of 12 animals were filled with the GTGC composites and another 12 unreconstructed rabbits were considered as controls. Three rabbits were examined for each group in every time period at 2, 4, 8 and 12 weeks after operation. There was no evidence of adverse tissue reaction to the GTGC composite. In addition, examination with light and fluorescent microscopy revealed a significantly greater amount of new bone ingrowth in the GTGC group at the same implantion time as compared with the controls. Therefore, the GTGC composite could serve as a useful substitute when repairing bone defects.

Animals↗

Coralline-sulfate bone substitutes.

Filling irregular defects caused by trauma or surgery with particulate bone substitutes usually results in migration of the particles from the wound. Coralline blocks have been used successfully to replace diseased bone. Immobilizing coralline particles should be useful in repairing bone defects. Coralline particles of < 45 microns were blended with < 45 microns particles of calcium or zinc sulfate (10%, 20% or 30%). Five gram blocks (20 x 10 mm) of the mixture were pressed at 800 pounds force. Blocks of coral-calcium sulfate were heated at 1000 degrees C and coral-zinc sulfate at 500 degrees C for two hours. The heated blocks were cooled, crushed and sized to < 45 microns particles. Distilled water (200-240 microliters) was added to 210 mg of coralline or coralline-sulfates. A circular rubber mold (10 x 4 mm) was filled with the paste and allowed to harden. Hardness was tested by applying pressure to the tablets at four minute intervals. Consistency equivalent to hardened plaster of Paris was recorded as maximum hardness. Coralline alone did not harden on addition of water. Mixing sulfates with coralline immobilized the particles to maximum hardness within 60 minutes on addition of water. Variation in the amounts of sulfate added (10%-30%) to coralline did not affect the hardening characteristics of the composite.

Biocompatible Materials↗

Microstructural and in vitro characterization of SiO2-Na2O-CaO-MgO glass-ceramic bioactive scaffolds for bone substitutes.

In the present research work, the preparation and characterization of bioactive glass-ceramic scaffolds for bone substitutes are described. The scaffolds were prepared by starch consolidation of bioactive glass powders belonging to the SiO2-Na2O-CaO-MgO system using three different organic starches (corn, potatoes and rice) as reported in a previous screening process. The scaffolds, characterized by scanning electron microscopy, showed a porous structure with highly interconnected pores. The pores sizes assessed by mercury intrusion porosimetry put in evidence the presence of pores of 50-100 microm. The structure of the scaffolds was investigated by X-ray diffraction and revealed the glass-ceramic nature of the obtained material. The mechanical properties of the scaffolds were evaluated by means of compressive tests on cubic samples and the obtained results demonstrated their good mechanical strength. The in vitro bioactivity of the scaffolds was tested by soaking them in a simulated body fluid (SBF) and by subsequently characterizing the soaked surfaces by SEM, EDS and X-ray diffraction. Good in vitro bioactivity was found for the starting glass and for the obtained scaffolds. Moreover, the scaffold bioresorption, tested by measuring the samples weight loss in SBF at different periods of time, showed a partial resorption of the scaffolds. Cell culture testing of the three different scaffolds indicated no differences in cell number and in alkaline phosphatase activity; the morphology of the osteoblasts showed good spreading, comparable to bulk material which was used as the control.

Body Fluids↗

No effect of Osteoset, a bone graft substitute, on bone healing in humans: a prospective randomized double-blind study.

We studied the effects of a newly marketed bone substitute, Osteoset, on bone healing in a tibial defect in humans. 20 patients undergoing an ACL (anterior cruciate ligament) reconstruction with bone-patella tendon-bone graft were block-randomized into 2 groups of 10 each. In the treatment group, the tibial defect was filled manually with Osteoset pellets, in the control group the defect was left empty. CTs of the defect were taken on the first day after the operation, 6 weeks, 3 and 6 months postoperatively. We found about the same amount of bone in the defect in the Osteoset and control groups after 6 weeks, 3, and 6 months. In the control group, but not in the Osteoset group, the bone volume increased from 6 weeks to 3 months. The Osteoset pellets were almost resorbed after 6 weeks.

Adult↗

Comparison of 3 bone substitutes in canine extraction sites.

PURPOSE: The purpose of this study was to evaluate the healing response with 3 different bone substitute materials in extraction sites in the dog. MATERIALS AND METHODS: Four dogs had their mandibular and maxillary premolars extracted atraumatically. The sites were immediately grafted with anorganic bovine bone (Bio-Oss, Osteohealth, Shirley, NY), Bone Source (Leibinger, Inc, Kalamazoo, MI), or Embarc (Lorenz Surgical, Jacksonville, FL), or left untreated as a control. After 8 weeks, the sites were removed for histologic evaluation of bone fill and the healing response. RESULTS: All sites healed well without signs of infection. No significant differences were noted in the shape of the ridges between groups. The control sites had radiographic bone fill by 8 weeks. The Bio-Oss sites showed bone fill with a similar appearance to the control sites. The Bone Source and Embarc sites showed implant material taking up most of the extraction site. In all sites the control and Bio-Oss sites had significantly more bone formation than the Embarc and Bone Source sites (P <.05). The control sites contained woven bone. The Bio-Oss sites were similar to the control sites, but with remnants of Bio-Oss in the bone. The Bone Source and Embarc sites were filled predominantly with the graft material without evidence of resorption and replacement of the materials, and with minimal bone formation. CONCLUSIONS: Based on this study, the control and Bio-Oss sites were similar, with bone filling most of the extraction site. The other 2 materials did not show replacement with bone.

Alveolar Bone Loss↗

SDS-PAGE analysis of the protein layers adsorbing in vivo and in vitro to bone substituting materials.

The composition of the protein layer adsorbed to the bone substituting materials, hydroxyapatite, beta-whitlockite, titanium and aluminium, in vivo (intramuscularly in guinea pig) and in vitro, was investigated using SDS-gel electrophoresis (SDS-PAGE). After in vivo implantation for 1 d mainly proteins with molecular weights between 10,000 and 20,000 were adsorbed. After 3 months the biolayer of the implanted biomaterials also contained proteins with molecular weights 35,000, 45,000, 60,000 and 200,000. No large qualitative differences in protein composition of the biolayers on the various implanted materials were found. In vitro incubation with human serum resulted in binding of proteins with estimated molecular weights of 30,000, 60,000 (albumin), 200,000 and greater than 200,000. It is suggested that the differences between in vivo and in vitro protein adsorption are due to proteolysis occurring in vivo in the vicinity of the implanted material.

Adsorption↗

Allograft and alloplastic bone substitutes: a review of science and technology for the craniomaxillofacial surgeon.

Bone healing is a complex and multifactorial process. As such, there are numerous steps in the process to which intervention can be directed. This has given rise to many bone graft technologies that have been used to regenerate bone, creating, perhaps, a bewildering array of options. The options that surgeons have the most familiarity with are the ones that have been available the longest (i.e., autograft and allograft). Although useful for the widest spectrum of clinical applications, limitations of these grafts has prompted the development of new materials. Demineralized bone matrix formulations and synthetic ceramic materials are now being used with greater frequency. These biomaterials have demonstrated their usefulness in facial plastic and reconstructive surgery with their ability to augment and replace portions of the craniofacial skeleton. The purpose of this article is to describe and discuss the allograft and alloplastic bone grafting technologies so that the reader can consider each in the context of the others and gain a better appreciation for how each fits into the universe of existing and emerging treatments for bone regeneration.

Biocompatible Materials↗

Powdered eggshell: a pilot study on a new bone substitute for use in maxillofacial surgery.

The present study is a preliminary report on the use of hen's eggshell as a possible bone substitute. In the first part of the study, particles ranging from 400 microns to 600 microns in diameter were bioassayed in an intramuscular pouch in rodents. This material was found to be biocompatible, but appeared not to have osteoinductive capacities. In the second and third part of the study, this material was used as an interpositional graft material in critical-size defects of rat mandibles and rabbit skulls. At 2 months, a morphologic restoration was obtained using the graft, but the healing was only achieved by fibrous union. In the fourth part of the study, the material was experimented on as an onlay bone graft on rabbit mandibles. A 6-month follow-up of the implant confirmed its stability. In conclusion, the use of this safe and inexpensive material is suggested for filling limited bone defects in non-weight-bearing areas. The use of eggshell powder for bone augmentation may also be considered, after further studies, to assess its long-term stability.

Animals↗

Closure of rabbit calvarial critical-sized defects using protective composite allogeneic and alloplastic bone substitutes.

This study evaluated the repair of critical-sized cranial vault defects in thirty New Zealand white rabbits using various allogeneic and alloplastic bone substitutes designed to provide mechanical protection to the brain as well as osteoinductivity. The strategies employed included demineralized bone matrix (DBM), a putty used in combination with a rigid resorbable plating system as a protective covering and calcium phosphate cement (CPC) combined with native partially purified bone morphogenetic protein (BMP). Bilateral critical-sized defects measuring 15 mm in diameter were created in the parietal bones of 30 adult male New Zealand white rabbits. They were divided into three groups with ten animals in each. Group 1 had one defect left unfilled as a control while autogenous bone was placed in the defect on the other side. In Group 2 a rigid resorbable copolymer membrane, Lactosorb (Lorenz Surgical, Jacksonville, Florida), was placed over both defects to cover them and protect the underlying tissues. The pericranial aspect of one defect was left unfilled while the other defect was filled with DBM putty. Group 3 had a CPC, Mimix (Lorenz Surgical, Jacksonville, Florida), placed into one of the defects while the defect on the other side was filled with the same CPC in combination with BMP in a concentration of 25 mg/mL. Bone healing was assessed clinically, radiographically, and histomorphometrically. All unfilled controlled defects, the defects covered with the resorbable Lactosorb membrane and those filled with calcium phosphate cement alone, healed with a fibrous scar. Defects reconstructed with DBM putty in combination with the resorbable Lactosorb membrane and calcium phosphate in combination with BMP healed with bone bridging the entire defect. This was obvious radiographically where the defects appeared completely filled with a dense radiopaque tissue. Histological analysis demonstrated that specimens where DBM putty was used in combination with the resorbable Lactosorb membrane had 67.7% new bone fill at 6 weeks and 84.0% at 12 weeks. Resorption of DBM particles was evidenced by the presence of osteoclastic activity and by the significant decrease in the size of the demineralized bone particles. In the calcium phosphate groups where BMP was added to the bioimplant there was 45.8% new bone formation at 12 weeks. The utilization of a composite consisting of DBM with resorbable Lactosorb membrane or a composite of calcium phosphate cement composite with BMP promoted complete closure of critical-sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks. The complete bone bridging observed with these composites suggests that they could be used to enhance the protection of intracranial contents following craniofacial surgical procedures.

Animals↗