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Opposite effects of recombinant human transforming growth factor-beta 1 on bone regeneration in vivo: effects of exclusion of periosteal cells by microporous membrane.

The efficacy of local delivery of recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) to promote bone regeneration, with or without cellular contribution from the periosteum, was evaluated in transosseous defects. Implantation of rhTGF-beta 1 into 5 mm in diameter "critical size defects" in the rat mandible resulted in a dose-dependent (0.1-20 micrograms/defect) bone bridging at both 12 and 24 days, independent of the type of delivery system [3% methyl cellulose gel, porous CaCO3 particles, or poly(lactide-co-glycolide) beads]. The bridging, however, never exceeded 24% at 12 days or 34% after 24 days. In contrast, when access of cells from the periosteum to the defect was prevented by means of microporous expanded polytetrafluoroethylene barrier membranes (GORE-TEX membrane), rhTGF-beta 1 caused a dose-dependent inhibition of bone regeneration. The bioactivity of the growth factor was confirmed by implantation of 5 or 10 micrograms rhTGF-beta 1 in 12 mm in diameter bicortical defects in rabbit calvaria, which resulted in complete bone healing within 28 days, whereas control defects displayed a bridging of 40%-50%. The findings support the concept, based on in vitro experiments by others, that TGF-beta 1 primarily has a proliferative effect on cells already committed to the osteoblastic lineage, but also imply that TGF-beta 1 may be inhibitory to induction of osteogenic cells in vivo.

Animals↗

Bone regeneration through transplantation of genetically modified cells.

To the author's knowledge, the rabbit is the largest animal model used to explore bone regeneration with genetically modified cells. This technology needs to be expanded to larger animal models that represent a more clinically relevant application in which cells are isolated from the animal, expanded ex vivo, genetically modified, and implanted in a critical-size bone defect in the donor animal. Furthermore, optimization of the vector type, vector dose, cell dose, and carrier material choice must be accomplished in animal models before clinical investigation is initiated. Most research has focused on a single osteoinductive protein; however, multiple proteins may synergize to further enhance bone formation. In conclusion, transplantation of genetically modified cells provides a new opportunity to improve bone tissue regeneration.

Animals↗

Exogenously regulated stem cell-mediated gene therapy for bone regeneration.

Regulated expression of transgene production and function is of great importance for gene therapy. Such regulation can potentially be used to monitor and control complex biological processes. We report here a regulated stem cell-based system for controlling bone regeneration, utilizing genetically engineered mesenchymal stem cells (MSCs) harboring a tetracycline-regulated expression vector encoding the osteogenic growth factor human BMP-2. We show that doxycycline (a tetracycline analogue) is able to control hBMP-2 expression and thus control MSC osteogenic differentiation both in vitro and in vivo. Following in vivo transplantation of genetically engineered MSCs, doxycycline administration controlled both bone formation and bone regeneration. Moreover, our findings showed increased angiogenesis accompanied by bone formation whenever genetically engineered MSCs were induced to express hBMP-2 in vivo. Thus, our results demonstrate that regulated gene expression in mesenchymal stem cells can be used as a means to control bone healing.

Animals↗

[Reparative bone regeneration after aseptic necrosis of the femoral head as influenced by 1-chloromethylsilatrane treatment].

The aim of this work was to study the effect of 1-chloromethyisilatranum on the processes of reparative bone regeneration in experimentally induced aseptic femoral head necrosis. Aseptic femoral head necrosis was modeled in 4 Chinchilla rabbits by destruction of spongy substance of femoral neck and cutting of ligamentum teres of its head. Rabbits of the experimental group were injected with 0.4 ml of 1% solution of 1-chloromethylsilatranum on postoperational days 5, 10, 15 and 20 into the damaged femoral head and close to the damaged joint. Animal were sacrificed by air embolism 5 weeks from the start of an experiment. Necrotic and repair processes in hip joints from damaged and intact sides were assessed radiologically and histologically prior to sacrifice. In rabbits of both control and experimental groups extensive aseptic necrosis of hip joints was found. The osseous tissue of damaged hip joints of experimental animals contained the chains of osteoblasts actively producing new bone matrix. Foci of bone regeneration were found both in the deep and peripheral regions of the epiphysis, which is indicative of active processes of bone repair. The results obtained suggest that administration of organic-silicon drug 1-chloromethylsilatranum stimulates (optimizes) the processes of repair osteogenesis following aseptic femoral head necrosis in experimental animals. Application of this preparation appears to be very promising.

Animals↗

The use of implantoplasty and guided bone regeneration in the treatment of peri-implantitis: two case reports.

A variety of treatment modalities have been proposed for the management of peri-implantitis. These are mostly based on empiric experience and use the systemic administration of an antibiotic in conjunction with surgical intervention. To ensure decontamination of the affected implant surface(s), chemical and/or mechanical debridement is used. For textured implant surfaces, detoxification using implantoplasty could also give favorable results when used as part of the procedure. Two cases are reported in which implants developed localized peri-implantitis lesions. Implantoplasty followed by topical tetracycline decontamination was used in conjunction with guided bone regeneration. In both cases, the procedures were effective in arresting disease and regenerating lost bone. These results suggest that the technique holds promise and should be investigated further.

Adult↗

Microbiologic and clinical study of polytetrafluoroethylene membranes for guided bone regeneration around implants.

This study determined the microbiota of the mucosa- and implant-facing parts of expanded polytetrafluoro ethylene augmentation material, and the influence of major periodontopathogens on the healing process associated with guided bone regeneration around dental implants. Seventeen patients with nine dehiscence and eight extraction defects were studied. Prior to surgery and at membrane removal, microbial morphotypes, total viable counts, and the occurrence of selected microbial species were examined by phase-contrast microscopy, nonselective and selective cultures, and DNA probes. Nine sites with submerged barrier membranes throughout the 9-month study were free of cultivable microorganisms and experienced significantly more osseous healing than eight sites with prematurely exposed membrane. Patients with few or no deep periodontal pockets demonstrated significantly fewer residual osseous defects than patients showing several pockets of increased depths. In addition, patients with prematurely exposed membranes revealed several deep periodontal pockets. Three patients with less than 1 mm of osseous gain yielded either Porphyromonas gingivalis or Actinobacillus actinomycetemcomitans. Peptostreptococcus micros occurred in high proportions in seven of the eight patients with premature membrane exposure and inadequate osseous healing. These findings associate putative periodontal pathogens with unsuccessful guided bone regeneration. The control of periodontal pathogens in the oral cavity prior to placement of barrier membranes around implants might increase the prognosis of osseous regeneration.

Adolescent↗

[Bone regeneration on hard palate after palatal surgery on cleft palate and the relative factors].

OBJECTIVE: Attending to observe the bony healing on hard palate after palatal repair, and to discuss the factors affecting on it. METHODS: 52 patients with repaired cleft palate over 5 years postoperatively were examined, the CT scan of head was taken. The incidence of the bone regeneration among the patients examined was calculated, the position and quality of bone tissue were measured according to the CT images. After all, analysis was applied to evaluate the factors affecting on the bone tissue formation. RESULTS: Formation of bone bridge was found in the 37 cleft gaps out of 52 patients (71%), the ratio of the sex among the patients who had bone bridge was 1:1, there was no obvious difference between unilateral and bilateral cleft palate. Considering the operation age with the bone formation, the highest percentage of bone bridge formation fell into the group of 4-7 years old, and the most occurring region were in premolar and anterior part of molar area. CONCLUSION: There could be bony healing(regeneration bone tissue RBT) after palatal repair on cleft palate patients. The operation age could be an important affecting factor to RBT, but the sex and the clinical type of cleft palate make no difference on the bone tissue formation.

Age Factors↗

Methods for the study of bone regeneration in lengthening of the limbs.

In addition to standard radiography the authors used two other methods, echography and dichromatic bone densitometry, in the evaluation of bone regeneration in patients submitted to lengthening of the lower limbs. They report their findings and conclusions on the value of these methods.

Bone Lengthening↗

Characteristics of newly formed bone during guided bone regeneration: observations by immunohistochemistry and confocal laser scanning microscopy.

The purpose of this study was to investigate the characteristics of new bone formation during guided bone regeneration (GBR) using immunohistochemistry and confocal laser scanning microscopy. e-PTFE membranes were applied to defects created in the tibiae of rats, and some animals were sacrificed 6, 8, or 10 days later. Serial paraffin sections were cut, stained with H-E, and examined to analyze the ratio of new bone formation. Immunohistochemical staining with a monoclonal antibody specific for PCNA was used to evaluate the proliferating activity. In other experimental rats, calcein was injected at 6, 8, and 10 days after the surgery, and the animals were sacrificed 48 hr after injection. Their tibiae were removed, and Villanueva bone staining was performed before observation using confocal laser scanning microscopy to investigate the mineralization of new bones. The bone occupation ratio increased day by day, but the experimental groups had significantly higher ratios than control groups (without membrane) at each of the time periods. However, PCNA positive cells decreased over time in all groups, and there were no significant differences among the groups. Mineralization occurred more rapidly in the experimental groups than in the control groups. These results suggest that GBR accelerates the migration of osteogenic cells, the formation of new bone, and mineralization in the defect created by the e-PTFE membrane.

Animals↗

Bone regeneration in extraction sites. Part 1: The simultaneous approach.

Implant placement in an extraction site is a frequent procedure in oral implantology. The concept of guided tissue regeneration to restore the alveolar ridge has expanded the available options for treatment of complicated cases. Implants can be placed in an extraction site at the time of surgery, and 3 to 4 weeks or 8 to 12 weeks after extraction in the simultaneous approach with guided bone regeneration. Four cases of implants placed in defective extraction sites with simultaneous guided bone regeneration are presented. Timing, surgical management, and complications are described.

Adult↗

Measuring the efficacy of rhBMP-2 to regenerate bone: a radiographic study using a commercially available software program.

This radiographic study evaluated the efficacy of different concentrations of rhBMP-2 to regenerate bone in alveolar defects in the anterior maxilla. The study was performed using reasonably standardized CT examinations and the Simplant program. The radiographic measurements were further refined by careful standardization of the measured regions of interest. There was a statistically significant difference in bone formation between subjects treated with a concentration of 1.5 mg/mL rhBMP-2 compared with each of the other groups. There was no statistically significant difference in bone volume between any of the other groups. None of the groups showed a loss in bone volume.

Alveolar Bone Loss↗

Histologic evaluation of the osteoinductive property of autogenous demineralized dentin matrix on surgical bone defects in rabbit skulls using human amniotic membrane for guided bone regeneration.

The aim of this investigation was to evaluate the osteoinductive property of autogenous demineralized dentin matrix (ADDM) on experimental surgical bone defects in the parietal bone of rabbits using the guided bone regeneration (GBR) technique incorporating human amniotic membrane (HAM). Thirty-six rabbits were divided into 2 groups, HAM and ADDM+HAM. It was possible to conclude that HAM did not interfere with bone repair and was resorbed. Slices of ADDM induced direct bone formation and were incorporated by the newly formed bone tissue and remodeled. The bone defects healed faster in the ADDM+HAM group than in the group with HAM only.

Absorbable Implants↗

Effects of guided bone regeneration with non-resorbable and bioabsorbable barrier membranes on osseointegration around hydroxyapatite-coated and uncoated threaded titanium dental implants placed into a surgically-created dehiscence type defect in rabbit tibia: a pilot study.

The purpose of this study was to evaluate the effects of guided bone regeneration (GBR) with either a non-resorbable (ePTFE) or bioabsorbable barrier membrane (RSLT) on osseointegration and extent of bone formation around hydroxyapatite-coated (HA) and uncoated threaded titanium (Ti) dental implants placed into surgically-created dehiscence type defects in rabbit tibia. A dehiscence type bone defect, approximately 3 mm in width and height was surgically created on the outer surface of the bone in each tibia of 9 rabbits. For the conventional group, either a HA or a Ti implant was then placed at this site. After the same procedure was performed as in the conventional group, the implant site of the GBR group was covered with either an ePTFE or a RSLT. After 4 months, the rabbits were sacrificed. Specimens were prepared and examined histometrically. It was found that the mean percentage of osseointegration tended to increase in HA compared to Ti implants, both with and without membranes. There was a tendency that the extent of newly regenerated bone was higher in the GBR group than that in the conventional group.

Absorbable Implants↗

Autogenous and xenogeneic bone grafts for the bone regeneration. A literature review.

The aim of this article is to investigate 2 groups of biomaterials widely used in the surgical procedures for bone regeneration in dentistry: autograft and xenograft bone. An insufficient bone volume is the main condition for the long life stability of osteointegrated implants. Thanks to the numerous surgical procedures and fervent research, the possibility to rebuild the bone is now much more predictable than in the past. This has provided the clinician with more solutions to handle complex situations. In the last decade, the demand for regenerative surgery for functional and aesthetic reasons has increased. The autogenous bone graft is considered the gold standard material for any regeneration procedures, because of its main properties: it is osteogenetic, osteoinductive and osteoconductive. The autogenous bone can be harvested from 2 different sites: the intraoral and the extraoral sites. Intraoral donor site are the symphysis of the mandible, the mandibular ramus and the maxillary tuberosity. Extraoral donor site are the iliac crest, the tibia and the skull. The xenogeneic bone graft is a graft that has been taken from a donor of another species. These natural materials, thanks to their chemical-physical characteristics similar to those of the human bone, show great osteoconductive properties.

Bone Diseases↗

Translational research for injectable tissue-engineered bone regeneration using mesenchymal stem cells and platelet-rich plasma: from basic research to clinical case study.

Translational research involves application of basic scientific discoveries into clinically germane findings and, simultaneously, the generation of scientific questions based on clinical observations. At first, as basic research we investigated tissue-engineered bone regeneration using mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) in a dog mandible model. We also confirmed the correlation between osseointegration in dental implants and the injectable bone. Bone defects made with a trephine bar were implanted with graft materials as follows: PRP, dog MSCs (dMSCs) and PRP, autogenous particulate cancellous bone and marrow (PCBM), and control (defect only). Two months later, dental implants were installed. According to the histological and histomorphometric observations at 2 months after implants, the amount of bone-implant contact at the bone-implant interface was significantly different between the PRP, PCBM, dMSCs/ PRP, native bone, and control groups. Significant differences were also found between the dMSCs/PRP, native bone, and control groups in bone density. These findings indicate that the use of a mixture of dMSCs/ PRP will provide good results in implant treatment compared with that achieved by autogenous PCBM. We then applied this injectable tissue-engineered bone to onlay plasty in the posterior maxilla or mandible in three human patients. Injectable tissue-engineered bone was grafted and, simultaneously, 2-3 threaded titanium implants were inserted into the defect area. The results of this investigation indicated that injectable tissue-engineered bone used for the plasty area with simultaneous implant placement provided stable and predictable results in terms of implant success. We regenerated bone with minimal invasiveness and good plasticity, which could provide a clinical alternative to autogenous bone grafts. This might be a good case of translational research from basic research to clinical application.

Aged↗

[The value of selected imaging techniques in evaluation of bone regeneration during limb lengthening].

The paper presents the value of different imaging techniques, including X-rays, ultrasonography, computed tomography and densitometry in the evaluation of bone regenerates during limb lengthening. Material consisted of 60 children, age ranging from 4 to 18 years who underwent surgery using the Ilizarov technique because of limb inequality. During of limb lengthening different imaging techniques were employed for monitoring regenerate growth and remodeling. The study showed that all the employed imaging techniques play an important role in monitoring bone regenerate remodeling at different stages of limb lengthening.

Adolescent↗

Porcine enamel matrix derivative enhances trabecular bone regeneration during wound healing of injured rat femur.

To elucidate the effects of enamel matrix derivative (EMD: Emdogain) on bone regeneration in rat femurs after drill-hole injury, defects in bone were filled with either EMD or its carrier, PGA, as control. On postoperative days 4 to 28, dissected femurs were examined by means of various morphological approaches. In both experimental groups, formation of trabecular bone, which was immunostained for bone sialoproteins (BSP), had occurred in the medullary cavities at cylindrical bone defects on Day 7 postoperatively. Cuboidal osteoblasts were clearly observed on these newly-formed BSP-positive bone trabeculae. On Days 7 and 14, many multinucleated giant cells, which strongly expressed cathepsin K, had appeared on these bone trabeculae, indicating active bone remodeling. In these bone trabeculae, Ca and P weight % and Ca/P ratio were similar to those of cortical bone, and there was no significant difference between the PGA- and EMD-applied groups. Bone volume fraction of newly-formed bone trabeculae on Day 7 postoperatively was significantly higher in the EMD-applied group than in the PGA-applied controls. Because of active bone remodeling and the marked decrease of bone volume, on Days 14 and 28 postoperatively, however, there was no longer a significant difference in trabecular bone volume fraction between the experimental groups. Our results suggest that EMD possesses an osteo-promotive effect on bone and medullary regeneration during wound healing of injured long bones.

Animals↗

The enhancement of bone regeneration by ultrasound.

Millions of fractures occur every year worldwide, with nearly 6.2 million fractures reported annually in the United States alone. Even though treatment methods have improved over the last few decades, 5-10% of fractures still show delayed healing. A significant subpopulation of these delayed healings do not heal by nine months and are thus termed non-unions. Experimental studies have shown some evidence that low intensity pulsed ultrasound stimulation (LIPUS) results in enhanced bone regeneration during fracture healing and callus distraction. LIPUS treatment has led to increased callus area and accelerated return of bone strength following fracture. Histological studies suggest that LIPUS influences all major cell types involved in bone healing, including osteoblasts, osteoclasts, chondrocytes and mesenchymal stem cells. The affect of LIPUS seems to be limited to cells in soft tissue, whereas cells in calcified bone seem not to be effected. In vitro cell culture studies as well as tissue culture studies have shown some effects on cell differentiation and protein synthesis. Even though the energy used by LIPUS treatment is extremely low, the effects are evident. The most probable source of the therapeutic benefits observed with LIPUS treatment involves nonthermal mechanisms that influence cell membrane permeability and increase cellular activity. Despite clinical and experimental studies demonstrating the enhancing effect of LIPUS on bone regeneration, the biophysical mechanisms involved in the complex fracture healing process remain unclear and requires further research.

Bone Regeneration↗