[Breakthrough in treating osteoporosis. Stimulation of bone regeneration with teriparatide].
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Bone Regeneration↗
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[Bone regeneration after filling of extensive cysts by means of bone collagen type 1].
It could be demonstrated by experimental studies on dogs that demineralized bone and bone products have a good osteogenetic potential which gives them a superior rating over artificial materials as replacement of autogenous bone transplants. The results of a prospective clinical study on 52 patients with 56 large mandibular or maxillary cysts are presented showing that bone collagen matrix type I is a good product for the filling of bone defects. Full reossification of a cyst was reaches as early as 8 months postoperatively in 20 cases. 32 defects had become substantially smaller. These results are discussed and compared to other methods mentioned in the literature.
Bone Regeneration↗
A composite polymer/tricalcium phosphate membrane for guided bone regeneration in maxillofacial surgery.
The aim of the study was the development of a resorbable membrane for guided bone regeneration (GBR) with improved biocompatibility, which should be stiff enough to avoid membrane collapse during bone healing. Combining a bioactive ceramic with a resorbable polymer may improve the biocompatibility and osteoconductivity of resorbable devices. The present article describes the preparation, the mechanical properties, and the in vitro degradation characteristic of a composite membrane made of poly(L, DL-lactide) and alpha-tricalcium phosphate in comparison to a membrane made of pure poly(L, DL-lactide). The tensile strength and the elastic modulus as well as the molecular weight of the membranes were measured after in vitro degradation in buffer at 37 degrees C up to 28 weeks. The initial tensile strength of the composite and the polymer membrane was 37.3 +/- 2.4 MPa and 27.7 +/- 2.3 MPa and the elastic modulus 3106 +/- 108 MPa and 3101 +/- 104 MPa, respectively. The mechanical properties remained constant up to 8 weeks and then decreased slowly until week 28. The molecular weight of both membranes decreased steadily from 170,000 D to 30,000 D. It was concluded that the mechanical requirements for a membrane for GBR were fulfilled by the composite membrane.
Absorbable Implants↗
Inhibition of natural killer cell-mediated lysis of tumor cells by normal and regenerating bone marrow.
The natural killer (NK) cells which can lyse certain tumor cells during brief incubation in vitro have also been postulated to be the cells responsible for natural resistance to transplanted hemopoietic cells in vivo. To test this hypothesis, we have now measured: 1) the ability of bone marrow cells to compete with tumor cells as targets for spleen NK cells and 2) the effect of a brief incubation with spleen cells on the hemopoietic grafting potential of bone marrow cells. Firstly, when CBA/J mouse spleen cells were incubated with 51Cr-labelled YAC tumor cells together with DBA/2 mouse bone marrow cells, tumor cell lysis was reduced compared with incubation of spleen cells with tumor cells alone. Tumor cell lysis was even less when post-irradiation regenerating bone marrow was used. Secondly, C57B1/6 mouse bone marrow cells incubated with an excess of DBA/2 mouse spleen cells showed a reduced ability to produce hemopoietic spleen colonies in irradiated 129/J mice, whereas incubation with either thymus cells or fewer spleen cells produced no such effect. The results show that, when incubated with spleen cells under the conditions of a standard NK cell assay, regenerating bone marrow cells competitively inhibit the killing of YAC tumor cells and bone marrow progenitor cells are rendered ineffective in their hemopoietic colony-forming potential (CFU-s). These findings suggest that certain hemopoietic progenitor cells and YAC tumor cells can both serve as targets for NK cells, consistent with the view that the spontaneous cytolysis of tumor cells in vitro and natural resistance to bone marrow transplantation in vivo are mediated by cells of a common lineage.
Animals↗
Vertical ridge augmentation with guided bone regeneration in association with dental implants: an experimental study in dogs.
AIM: To evaluate the effect of using guided bone regeneration (GBR) with a titanium-reinforced e-PTFE membrane in alveolar bone defects with titanium implants. MATERIAL AND METHODS: Following extraction of three mandibular premolars and a molar on both sides of the jaw in three dogs, alveolar bone defects (depth: 5-7 mm) were produced. After 4 months, three implants were inserted into each defect to a depth of approximately 4 mm, so that their coronal portion was protruding about 5 mm. Four sides in the dogs were assigned to a test group and the remaining two sides to a control group. The 12 implants in the test group were covered with a reinforced e-PTFE membrane. The space under the membrane was filled with peripheral venous blood from the animal, and the flaps were sutured over the membrane. The six control implants received no membrane before the suturing of the flaps to complete wound closure. The animals were sacrificed after 6 months, and non-decalcified histological specimens of the implants and surrounding tissues were prepared. RESULTS: Histologic and histomorphometric analyses revealed a significantly (Mann-Whitney test; P=0.08) larger amount of bone fill in the test group (mean=57.42%) than in the controls (mean=11.65%), and clinical evaluation of one test site showed that the implants were completely covered with tissue resembling bone. In most of the specimens, bone had grown in height close to, or in direct contact with the membrane. However, the new bone generally was not in direct contact with the implants. Regularly, a zone of dense connective tissue was interposed between the implants and the newly formed bone. CONCLUSION: The formation of even considerable amounts of bone following vertical ridge augmentation with GBR and implants was not accompanied by predictable osseointegration of the implants.
Alveolar Bone Loss↗
Ex vivo gene therapy in autologous bone marrow stromal stem cells for tissue-engineered maxillofacial bone regeneration.
This study examines the clinical relevance of tissue engineering integrating gene therapy and polymer science to bone regeneration. Bilateral maxillary defects (3 x 1.2 cm(2)) in 20 miniature swine were bridged with a bioresorbable internal splint. Constructs were created using ex vivo adenovirus bone morphogenetic protein (BMP)-2-mediated gene transfer to the expanded bone marrow mesenchymal stem cells (MSCs) 7 days before implantation. Controls were performed using adenovirus beta-galactosidase. The BMP-2 cell/construct displayed white solid bone formation after 3 months. Meanwhile, the hematoxylin and eosin and Von Kossa stains demonstrated exhibited mature woven bone with good mineralization. Additionally, three-dimensional computer tomography imaging revealed a nearly complete infraorbital rim repair. Quantitative analysis demonstrated a significant difference (P<0.001) in bone formation. Finally, biomechanical testing revealed no statistically significant difference in the maximal compressive strength of new bone formed by BMP-2 cell constructs and the normal maxilla. The data evidenced de novo bone formation capable of sustaining axial compressive loads. The measurement results showed that ex vivo replication defective adenovirus-mediated human BMP-2 gene transfer to MSCs enhances autologous bone formation in the repair of maxillary defects.
Adenoviridae↗
[Experimental study on stimulation of guided bone regeneration by acid fibroblast growth factor].
OBJECTIVE: To investigate the effect of acid fibroblast growth factor (aFGF) on guided bone regeneration (GBR), to study whether aFGF can promote the repairing ability of GBR in bone defect. METHODS: 10 mm long segmental defects were created in the diaphyses of both radii in 16 New Zealand rabbits. The defect was bridged with a silicon tube. Human recombinant aFGF was instilled into the tube on the experimental side, while the contralateral tube was instilled with saline as control group. The radiographic, gross and histologic examination of the samples were analyzed at 2, 4, 6 and 8 weeks after operation. RESULTS: On the experimental side, there was new bone formation in the bone medullary cavity, the endosteum and the section surface of the cortex at 2 weeks. At 4 weeks, at the center of the blood clot in the tube there was new bone formation and bone defect was completely healed at 8 weeks. On the control side, new bone formation was less in every period compared with that of the experimental side. At 8 weeks, there was only partial healing of the bone defect. CONCLUSION: It can be concluded that aFGF can promote new bone formation and facilitate GBR in bone defect.
Animals↗
Engineering bone regeneration with bioabsorbable scaffolds with novel microarchitecture.
Critical-sized defects (CSDs) were introduced into rat calvaria to test the hypothesis that absorption of surrounding blood, marrow, and fluid from the osseous wound into a bioabsorbable polymer matrix with unique microarchitecture can induce bone formation via hematoma stabilization. Scaffolds with 90% porosity, specific surface areas of approximately 10 m2/g, and median pore sizes of 16 and 32 microm, respectively, were fabricated using an emulsion freeze-drying process. Contact radiography and radiomorphometry revealed the size of the initial defects (50 mm2) were reduced to 27 +/- 11 mm2 and 34 +/- 17 mm2 for CSDs treated with poly(D,L-lactide-co-glycolide). Histology and histomorphometry revealed scaffolds filled with significantly more de novo bone than negative controls (p < 0. 007), more osteoid than both the negative and autograft controls (p < 0.002), and small masses of mineralized tissue (< 15 mm in diameter) observed within the scaffolds. Based on these findings, we propose a change in the current paradigm regarding the microarchitecture of scaffolds for in vivo bone regeneration to include mechanisms based on hematoma stabilization.
Absorbable Implants↗
[A case report of implantation in augmented bone by guided bone regeneration technique].
PATIENT: A 53-year-old female with root fracture of the second premolar in the right mandible underwent implant therapy. After extraction, the GBR (guided bone regeneration) technique was applied to the bone defect in June 2000. At 6 months after GBR, implants were placed in the augmented bone. The final prosthesis was restored in July 2001. DISCUSSION: The bone around the implants was evaluated by using X-ray CT images, before and after GBR, and three years after final restoration. The three images showed the same bone conditions around the implants. CONCLUSION: It is important to evaluate bone condition around implants using X-ray CT. Bone defects can be augmented by the GBR technique, and the bone condition around the implants was stable after function.
Bone Regeneration↗
[Experimental studies on exterior bFGF for enhancement of membrane guided bone regeneration].
These studies sought to evaluate the promoting effect of the exterior bFGF on membrane guided bone regeneration (MGBR). Animal models of MGBR covered with PDLLA membrane tube in bilateral radii were established in 40 New Zealand white rabbits. The membrane tubes on the left side were filled with bFGF 40 microg/100 microl and those on the contralateral side were filled with 100 microl 0.9% NaCl solution as control. The specimens were collected at 2, 4, 8, 12 weeks postoperatively. General observation, X-ray, histological grading and HE staining,and biomechanical examination were applied to studies on the repair of the models of MGBR in the two groups. Two weeks after operation, a sealed room was formed between the two bone fragments where the soft tissues covered the membrane tube. Twelve weeks after operation, PDLLA membrane became fragile and its tube shape was being maintained. Histologically, in the bFGF group numerous newly formed bone trabeculae were seen at 2 weeks after operation the radial defects had healed and the bone reconstruction and remodling had begun by the 12th week. The histological image analysis showed that the values of mean diameter and the area of new bone trabeculae in the bFGF group were higher than those in the control group (P<0.05) at 2 weeks and 4 weeks; however, there were no significant differences in these aspects between the two groups (P>0.05) at 8 and 12 weeks. The strength of the newly formed bone in the bFGF group was higher than that in the control group at 12 weeks postoperatively (P<0.05). Therefore, the authors concluded that bFGF could promote the new bone formation and biomechanical strength in the MGBR model.
Animals↗
[Experimental study on acellular bovine pericardium guided bone regeneration material].
OBJECTIVE: To choose the best procedure on preparation of acellular bovine pericardium (ABP) guided bone regeneration (GBR) material. METHODS: The BP was decellularized with 0. 25% Trypsin + 0.5% Triton X-100. The acellular bovine pericardiums (ABPs) were treated with phosphate-buffered saline(PBS) (group A), 95% glycerol (group B), EDAC (group C), and EDAC and 95% glycerol (group D) respectively. The treated ABPs were implanted subcutaneously in the back of SD rats respectively at random and no material was implanted as control. Seven rats were sacrificed at 2 weeks, twelve at 4 weeks, twelve at 8 weeks, seven at 16 weeks. Local reaction was studied grossly. The amount of antigen presenting cell (APC) and the percentage of ABP degeneration were reckoned by images analysis system. RESULTS: The ABPs were replaced by fibroblasts completely in group A at 8 weeks, in group C at 16 weeks, but only less than 50% till 16 weeks in groups B and D. In all groups, the depth of surrounding fibres attenuated time-dependently. The APC amount of the groups B and D was higher than that of the control group, and the ABP of the groups B and D degraded partly at 16 weeks. CONCLUSION: The ABP treated with EDAC can be replaced by the surrounding tissues and has good biocompatibility.
Animals↗
A new porous hydroxyapatite for promotion of bone regeneration in maxillary sinus augmentation: clinical and histologic study in humans.
PURPOSE: This study was undertaken to evaluate clinically, histologically, and immunohistochemically the use of a new porous hydroxyapatite (HA) (B. Agra, Cabon, Milan, Italy) as a grafting material for maxillary sinus augmentation with simultaneous implant placement. MATERIALS AND METHODS: A total of 28 titanium implants were placed in 12 patients with an average of 4.5 mm of bone on the sinus floor. HA granules were packed around the implants in the sinus cavity. After a healing period of 5 to 6 months, second-stage surgery was carried out. In 5 patients, bone cores were harvested from grafted areas and processed for histology and immunocytochemistry. RESULTS: All implants were clinically stable at second-stage surgery and were followed for an average of 3 years. The histology showed newly formed bone in direct contact with the HA granules. Immunohistochemistry showed the presence of large quantities of bone sialoprotein and osteopontin in and around the granules of HA. DISCUSSION AND CONCLUSION: This study suggests that a new porous HA accommodated sinus floor augmentation in patients with 3 to 5 mm of bone height preoperatively. By possibly attracting circulating biocomponents at sites of tissue repair, it may promote bone regeneration.
Adult↗
Bone regeneration in rabbit sinus lifting associated with bovine BMP.
Autogenous bone is considered the optimal grafting material for sinus lifting, although its harvesting causes great patient discomfort. Various approaches have been taken in order to obtain sinus lifting with preexisting tissue. However, because of the unsuitability of such tissue, additional materials have been required. Alternatively, biomaterials from humans or other animals are used. In this study, the efficacy of using morphogenetic bovine bone protein (BMPb) to augment the maxillary sinus floor was examined. Four grafting materials were employed: lyophilized bovine bone powder, absorbable collagen flakes, natural hydroxylapatite, and synthetic hydroxylapatite. Two groups of rabbits were studied. In one group, graft material only was used. In the other, graft material was combined with 0.5 mg BMPb. During 8 weeks of observation, polyfluorochrome tracers were injected in subcutaneous tissue to evaluate new bone- deposition periods. Following sacrifice, the samples were examined under fluorescent and light microscopes. Results indicated 33.34% more newly formed bone in BMPb animals than in controls. Graft-material resorption increased, but natural HA showed no significant alterations. The results show that the use of BMPb, although providing osteoinduction, might not promote sufficient bone formation. Nonetheless, this material could provide an alternative to autogenous grafts, thereby avoiding patient discomfort.
Animals↗
Improved bone regeneration and root coverage using a resorbable membrane with physically assisted cell migration and DFDBA.
Twelve patients with 2 Miller Class I or II buccal recession defects measuring > or = 3.0 mm were treated using the principles of guided tissue regeneration and followed for 12 months. The effectiveness of a polylactide (Guidor) resorbable membrane (GA sites) was compared to a combination treatment of polylactide membrane plus polyglactin root-lining mesh (Vicryl) and demineralized freeze-dried bone allograft (DFDBA) (GVB sites) designed to enhance cell migration and bone regeneration. There was 90% mean soft tissue root coverage for the GVB sites and 78% for the GA sites. The mean osseous dehiscence area coverage with hard tissue was 75% for GVB sites and 30% for GA sites.
Absorbable Implants↗
Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly(lactic acid) for bone regeneration.
Development of fibrous matrices of bioceramic-biopolymer nanocomposite offers great potential in the field of bone regeneration and tissue engineering. However, in order to produce electrospun fibers with homogeneous structure, it is essential for the ceramic powder to be fine and to remain stable in suspension. Herein, we developed a novel method whereby the bioceramic hydroxyapatite (HA) was kept in suspension in biopolymer poly(lactic acid) (PLA). The strategy was to introduce a surfactant hydroxysteric acid (HSA) between the hydrophilic HA powder and the hydrophobic chloroform-dissolved PLA. The HA nanopowder was dispersed effectively in HSA and mixed homogeneously with PLA. Continuous and uniform fibers were generated successfully with diameters of approximately 1-2 microm, and featured a well-developed nanocomposite structure of HA nanopowder-dispersed PLA. Initial cellular assays showed excellent cell attachment and proliferation and also enhanced expression of alkaline phosphatase at 7 days of culturing. The HA-PLA nanocomposite fibers may be potentially useful in tissue engineering applications, particularly as three-dimensional substrates for bone growth.
Bone Regeneration↗
Re-implantation of homologous, cultivated osteoblast-like cells for improvement of bone regeneration. An animal study.
The regeneration of osseous tissues after implantation of rat osteoblast-like cells cultivated in vitro was investigated. A cell line of rat osteoblast-like cells originating from explants of four inbred rats (Lewis) was established. The osteoblast-like cells were cultivated in vitro and re-implanted after 3 passages in cell culture into artificial femur defects of the same inbred Lewis rats. The cultivated osteoblast-like cells were embedded in bovine bone gelatine and implanted together with hydroxylapatite granulate (12 animals), pyrolized calf bone (12 animals) or without any additional material (12 animals). These bone replacement materials were used as a carrier for the osteoblast-like cells. After 10, 20, 40 and 80 days animals were killed and the treated femora were taken for histological examination and determination of bone growth rate. It was demonstrated that the cultivated osteoblast-like cells in this experiment had no measurable effect on quantitative bone growth, but caused a significant difference in the histological bone regeneration pattern.
Animals↗
Biological mediators for periodontal and bone regeneration.
In the past 25 years, significant advances in treatment have occurred in the area of periodontal and bone regeneration. Novel regenerative therapies have emerged based on an increased understanding of embryonic development and wound healing at the cellular and molecular level. Two approaches that have demonstrated significant regenerative potential include the administration of enamel matrix proteins and growth and differentiation factors. Current data regarding the use of enamel matrix proteins support their safety and efficacy. The use of recombinant growth and differentiation factors has been validated in preclinical and clinical trials. A new era of regenerative therapies has emerged, using biological mediators combined with scaffold materials to stimulate cellular processes required for the regeneration of oral tissues. The clinical application of these therapies will be to either replace or augment traditional regenerative treatments.
Alveolar Process↗
[Construction of guided bone regeneration membrane by tissue engineering in vitro].
In this study, porous polymer (PLA/PCL) membrane was first treated with ethanol to become hydrophilic, and then immersed into DMEM with 50% fetal bovine serum to enhance the affinity to cells. MSCs cultured in osteogenic medium were loaded into the membrane at density of 5 x 10(6)/cm2 for 7 days, and scanning electrical microscope was used to observe the growth of the MSCs. The growth of MSCs inside the constructs was functionally well, and the cells proliferated with the time of culture. We concluded from current study that the membrane had satisfactory biocompatibility and the constructs could be used to guided bone regeneration.
Animals↗