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PubMed2002

[Bone regeneration using bone morphogenetic protein (BMP)].

Bone morphogenetic protein (BMP) is one of the most promising osteoinductive substances and is expected to be applied clinically for bone reconstruction. BMP has restored critical-size bone defects in numerous animal experiments, but the evaluation of bone formation by BMP in primates is a prerequisite for its clinical application. We attempted to restore the mandible bone defects in primates using BMP. The implantation of BMP with the carrier completely regenerated the mandible bone defects in the young primates, and the occlusal function was restored by the dental implants inserted into the regenerated bone. Although the use of BMP alone to regenerate mandible bone defects in old monkeys produced inconclusive results, the combination grafts of BMP and bone marrow, which contained osteoprogenitor cells, were successful. Furthermore, the combination of BMP and the culture-expanded cells derived form bone marrow grafts regenerate the segmental bone defects in the mandibles of old monkeys. Thus, the implantation of BMP with the BMP-responding cells could restore large bone defects even in elderly patients.

English Abstract↗
PubMed2005

[The effect of platelet-rich plasma combined with autogenous bone graft for bone regeneration in bone defects].

The objective of the present study was to evaluate the effect of PRP on bone healing both quantitatively and qualitatively using histomorphometrical methods in a rabbit model. The examined materials were autogenous bone, PRP alone, a mixture of autogenous bone and PRP, and whole blood (as a control). These materials were implanted into artificial defects prepared in rabbit tibiae. The observation period was set at 1, 2, 3, and 4 weeks. All specimens were used for histologic evaluation and 2- and 4-week specimens were used for histomorphometrical evaluations. The bone quantity increased when autogenous bone was applied but the percentage of mature bone in the autogenous bone site was smaller than in the PRP applied site. The results of this study suggested that the quantity of newly formed bone increased when autogenous bone was applied, but not when PRP only was applied. However, PRP might accelerate bone maturation by activating bone remodeling. According to this study, the bone quality could be altered by the application of PRP.

Animals↗
PubMed1996

Long-term stability of osseointegrated implants in bone regenerated with the membrane technique. 5-year results of a prospective study with 12 implants.

The purpose of the present clinical study was to evaluate the 5-year results of the first 12 implants inserted at the University of Berne in regenerated bone following successful ridge augmentation with the membrane technique. The patients were recalled and examined with clinical and radiographic parameters routinely utilized in prospective studies with standard implants in non-regenerated bone. Based on clinical and radiographic findings, all 12 implants were considered successfully integrated according to strict criteria of success. The detailed analysis of clinical parameters revealed no differences to results of prospective studies on standard implants in non-regenerated bone. All implants demonstrated ankylotic stability which was confirmed by a mean Periotest value of -2.08. The radiographic analysis showed stable bone crest levels with a mean bone loss between the 1- and 5-year examination of 0.30 mm. However, 2 implants exhibited a bone loss of more than 1 mm between the 1- and 5-year examination. Therefore, the prognosis of these 2 implants seems questionable at the present time. It can be concluded that bone regenerated with the membrane technique reacts to implant placement like non-regenerated bone, since all 12 implants achieved successful tissue integration with functional ankylosis. Furthermore, this bone is also load-bearing, since all 12 implants maintained osseointegration over a 5-year period.

Alveolar Bone Loss↗
PubMed2000

Tissue-engineered bone regeneration.

Bone lesions above a critical size become scarred rather than regenerated, leading to nonunion. We have attempted to obtain a greater degree of regeneration by using a resorbable scaffold with regeneration-competent cells to recreate an embryonic environment in injured adult tissues, and thus improve clinical outcome. We have used a combination of a coral scaffold with in vitro-expanded marrow stromal cells (MSC) to increase osteogenesis more than that obtained with the scaffold alone or the scaffold plus fresh bone marrow. The efficiency of the various combinations was assessed in a large segmental defect model in sheep. The tissue-engineered artificial bone underwent morphogenesis leading to complete recorticalization and the formation of a medullary canal with mature lamellar cortical bone in the most favorable cases. Clinical union never occurred when the defects were left empty or filled with the scaffold alone. In contrast, clinical union was obtained in three out of seven operated limbs when the defects were filled with the tissue-engineered bone.

Animals↗
PubMed2005

VEGF-activated angiogenesis during bone regeneration.

PURPOSE: The aim of this study was to investigate the influence of controlled release of recombinant human vascular endothelial growth factor (rhVEGF(165)) on angiogenesis and osteogenesis in a mandibular defect model. MATERIAL AND METHODS: A total of 56 rabbits were operated and bicortical holes were placed at the lower border of the mandible. The defects were filled with type-I collagen, with collagen complexed with 0.8 mug rhVEGF(165), or left without any filling. After 3, 7, 14, and 28 days, specimens were taken and histologic, histomorphometric, and immunohistologic analyses were carried out concerning number of vessels, cross-sectional area of vessels, and area and density of regenerated bone. RESULTS: Bone formation occurred in a typical centripetal direction and showed all stages of bone regeneration and maturation. New vessel formation took place in front of the osteogenic regeneration front. The number of vessels increased in all groups until day 14, followed by physiologic regression in the control groups as opposed to persisting high numbers in the study group. The area of newly formed bone showed no difference to the control group but the density of regenerated bone was significantly higher in the study group. CONCLUSION: Blood vessels are an important component of bone formation and maintenance and the bone tissue differentiation is related to the local presence of blood vessels. The activation of angiogenesis using rhVEGF(165) leads to more intensive angiogenesis and bone regeneration.

Animals↗
PubMed2005

Implants in regenerated bone in patients treated for generalized aggressive periodontitis: a prospective longitudinal study.

The aim of this prospective longitudinal study of patients treated for generalized aggressive periodontitis (GAP) was the clinical, microbiologic, and radiologic longitudinal evaluation of implants placed into bone regenerated by the guided bone regeneration (GBR) technique. Ten patients with GAP who had lost either one or two maxillary incisors or premolars through periodontal disease and whose alveolar bone was neither high nor wide enough for implant placement were enrolled in the study. GBR was carried out in a two-stage procedure using titanium-reinforced extended polytetrafluoroethylene membranes and titanium screws. No bone graft or bone substitute materials were used. After 6 to 8 months, the membranes and supporting screws were removed, and a total of 15 implants (Nobel Biocare) were placed. The control group comprised 10 periodontally healthy patients who had a total of II implants (Nobel Biocare) placed in the maxilla (incisor and premolar region) without GBR because of aplasia, trauma, or endodontic lesions. All patients were examined 2 to 4 weeks before extraction of the nonretainable teeth (baseline) and again immediately after placement of the superstructure. Further examinations were performed within the framework of a 3-month recall schedule over a 3-year period. At each session, clinical parameters (probing pocket depths, bleeding on probing, gingival recession, clinical attachment level, Gingival Index, and Plaque Index) were recorded at teeth and implants, and the composition of the subgingival microflora was determined by dark-field microscopy and DNA probe. Intraoral radiographs were taken for control purposes at baseline, immediately after insertion of the superstructure, and 1 and 3 years later. The GBR technique yielded a horizontal and vertical bone gain of 4.5 to 7.0 mm in the GAP patients. The clinical, microbiologic, and radiologic findings indicated healthy periodontal and periimplant conditions in both patient groups throughout the study. However, a slightly increased attachment loss (0.65 mm) and bone loss (1.78 mm) were recorded at the implants in the regenerated bone after 3 years of loading. The 3-year implant survival rate was 100% in both groups. The possibility of continuous attachment loss and bone loss occurring at teeth and implants in regenerated bone cannot be ruled out in patients treated for aggressive periodontitis. The prognosis for the retention of the teeth and implants is thus open to question.

Adult↗
PubMed2002

Experimental tooth movement through mature and immature bone regenerates after distraction osteogenesis in dogs.

The purpose of this study was to verify the influence of tooth movement on tooth roots and periodontal tissues when teeth were moved into mature, well-organized, and mineralized regenerate bone created after distraction osteogenesis compared with immature, fibrous, and less-mineralized bone. Six 15-month-old male beagles underwent 10 mm of bilateral mandibular distraction osteogenesis. After 2-week (group 1) and 12-week (group 2) consolidation periods, third premolars were moved distally into the regenerate bone with 100 g of orthodontic force for 12 weeks. Simultaneously, second premolars were also moved distally as controls. After completion of tooth movement, the experimental animals were killed, and their tissues were harvested for histological evaluation. When premolars in groups 1 and 2 were compared, group 1 showed higher rates of tooth movement until the eighth week of experimental tooth movement (P <.05). The amount of tooth movement was significantly greater in group 1 than in group 2 or in the control teeth (P <.05). In group 1, we observed considerable root resorption extending into the dentin, and the thickness of the dentin became approximately half that of the controls at the compression side adjacent to the distraction gap. This root resorption extended from the cementoenamel junction to the root apex. In group 2, root resorption on the compression side reached the dentin, but the root resorption was less than in group 1. These results indicated that heavy force and early orthodontic tooth movement are not recommended when teeth are moved through regenerated bone created by distraction osteogenesis, to avoid tipping and severe root resorption.

Alveolar Process↗
PubMed2001

Implants in regenerated bone in a primate model.

BACKGROUND: Earlier publications from our laboratory described the use of guided bone regeneration to fill large bone voids in the mandible created through en bloc resection in primates. The present report describes placement of implants into the regenerated bone with subsequent prostheses construction and loading. METHODS: Lesions were created in the mandibles of 9 monkeys in a standardized mandibular defect of 8 x 19 mm. Reinforced expanded polytetrafluoroethylene membranes were placed in the animals and held in place with mini screws and sutures for anywhere from 1 to 12 months. No material was added to the defect. In each animal a root-form implant was placed 12 mm distal to the abutment teeth into the regenerated bone and was loaded with a prosthesis for 12 months. These implants were compared to original implants placed in the same monkeys years earlier in the same location in non-regenerated bone. Digital radiology and histomorphometry are described. RESULTS: The results show that root-form implants placed in regenerated bone show the same radiological and histomorphometric characteristics as in normal bone when loaded. In addition, the percentage of bone contact with implants seen in regenerated bone versus non-regenerated bone is the same when both are loaded (65 +/- 13% SD in regenerated bone versus 59 +/- 15% SD in non-regenerated bone). CONCLUSIONS: In a primate model root-form implants placed in regenerated bone and prosthetically loaded show no difference when compared to root-form implants placed in non-regenerated bone and prosthetically loaded.

Alveolar Bone Loss↗
PubMed1998

Guided jaw-bone regeneration using an experimental rabbit model.

The aims of this study were to evaluate the space-maintaining capacity of two biocompatible barrier materials and to assess the effect of barrier occlusiveness on the amount of regenerated bone. Defects were prepared in the edentulous area on both sides of the maxillas in 22 rabbits. The rabbits were divided into three groups. Gore-Tex augmentation material (GTAM) (ePTFE)-barriers were placed to cover the experimental defects and compared with totally occlusive or perforated titanium foils and uncovered control defects respectively. After four weeks of healing, histological analyses and morphometrical measurements demonstrated that the amount of regenerated bone tissue was about the same underneath the collapsed GTAM-barriers as in the controls. The highest degree of regeneration was obtained in defects underneath the titanium foils, particularly if they were perforated, whether or not they were covered by GTAM-barriers. It was concluded that the space-maintaining properties of a barrier may be at least as important as barrier occlusiveness when regenerating bone defects.

Animals↗
PubMed1997

Clinical trials on implants in regenerated bone.

The lack of a sufficient volume of healthy jaw bone was the most important local contraindication for the placement of dental implants in the 1980s. Thus, several attempts have been made in the past 10 years to develop new surgical methods for the reconstruction of lost jaw bone in potential implant patients. At present, methods such as guided bone regeneration utilizing barrier membranes or sinus lift procedures are widely used in dental offices. There are, however, some concerns about the efficacy and predictability of these procedures. There is a need to determine how new bone regenerative procedures should be properly evaluated. The goal of the present paper is to establish some guidelines for clinical trials on implants in regenerated bone. It is proposed that such trials should be conducted in two main phases according to predetermined endpoints. The first main phase evaluates the new bone regenerative procedure. This almost always requires an initial development period including step-by-step modifications to identify essential surgical factors for the achievement of successful treatment outcomes. At the end, the surgical protocol will be established in detail. This is followed by the validation period to evaluate efficacy and predictability of this surgical protocol in a clinical study with consecutively treated patients. After successful bone regeneration has been properly documented, the second main phase evaluates the implants inserted in regenerated bone in a prospective clinical study utilizing the same protocol as for implants in pristine, non-regenerated bone. This documentation allows the evaluation of tissue integration of these implants and their 5-year success rates.

Alveolar Ridge Augmentation↗
PubMedDate not supplied

Bone regeneration in standardized bone defects with autografts or bone substitutes in combination with platelet concentrate: a histologic and histomorphometric study in the mandibles of minipigs.

PURPOSE: To evaluate the effect of the addition of platelet concentrate (PC) to autografts or bone substitutes on bone regeneration in standardized bone defects. MATERIALS AND METHODS: Three standardized bone defects were prepared in both mandibular angles of 12 adult minipigs. The defects were grafted with autograft, anorganic bovine bone, or synthetic beta-tricalcium phosphate (beta-TCP). PC was added to only 1 side. The animals were divided into 4 groups, which were sacrificed at 4 different time points (1, 2, 4, and 8 weeks) for histologic and histomorphometric analysis. The concentrations of platelets and growth factors were measured to identify correlation to the histologic and histomorphometric results. RESULTS: No correlation was found between platelet count in whole blood and platelet count in PC (r(p) = 0.36). Furthermore, no correlation could be demonstrated between the platelet count of the PC and the concentrations of PDGF-AB (r(p) = -0.27) and TGF-beta (r(p) = 0.34). There were no signs of a stimulating effect of PC on bone formation in combination with autografts or bone substitutes at any time point (P = .89). Addition of PC did not alter the pattern of graft degradation. DISCUSSION: The present study underlines the need for further investigation to identify the optimal concentrations of platelets and combinations of growth factors to achieve a predictable stimulatory effect on bone regeneration. One of the first steps to achieve this goal will be the development of a reliable method for the procurement of PC. CONCLUSION: PC had no impact on bone formation and graft degradation in standardized bone defects in the mandibles of minipigs.

Analysis of Variance↗
PubMed2004

[Using platelet-rich plasma (PRP) to improve bone regeneration in implant bone defect].

OBJECTIVE: To evaluate the result of bone regeneration due to using PRP in combination with beta-TCP in bone defect adjacent to oral implantation. METHODS: Ten patients (6 males, 4 females, with an average age of 49.6 years) participated in this study. Seven of them underwent maxillary sinus augmentations, and 3 underwent GBR for peri-implant bone defects. PRP + beta-TCP was used in 4 cases and beta-TCP in other 6 as control. X-ray examinations were carried out prior to operation and in 1 week, at 3 months, 6 months after operation. After 4 - 6 months, 3 biopsy specimens were obtained at the time of the second stage operation in each group. RESULTS: Bone grafts healed well without any infection in all cases. Radiographs showed that bone grafts integrated together with the bone. The histological result showed that new bone was formed among particles of beta-TCP in both groups, but in PRP + beta-TCP group denser and better arranged woven bone was observed, and more new bone was formed into the micropores of the particles. CONCLUSIONS: The result in this study implied that PRP in combination with beta-TCP can improve bone regeneration in bone defect adjacent to oral implantation.

Adolescent↗
PubMed2004

[Alveolar bone regeneration stimulated by a combination of platelet-rich plasma and Cerasorb graft in Beagle dogs. Histological and histomorphometric studies].

Healing of extraction wounds was examined in an animal experiment model on Beagle dogs. After bilateral extraction of the premolars of 12 dogs the alveoli were filled up with a combination of beta-tricalcium phosphate (Cerasorb) graft and platelet rich plasma (PRP) on the experimental side, and with Cerasorb alone on the control side. Biopsy specimens were taken from the regenerating bone at 6, 12 and 24 weeks after surgery for histological study. Results of the histologic and histomorphometric examinations revealed that after 6 weeks the newly formed bone was significantly denser on the experimental side. After 12 weeks this difference became moderate, and after 24 weeks the bone forming activity was nearly equal on the two sides. These results suggest that local administration of Cerasorb and PRP results in more intense bone regeneration, especially in the early phase.

Alveolar Process↗
PubMed1998

Enhanced bone regeneration and formation around implants using guided bone regeneration.

This study investigated the use of a prototype expanded polytetrafluoroethylene membrane attached to bone with butyl-cyanoacrylate, in facilitating guided bone regeneration into bone defects and around titanium screws in rabbit femora. Two experimental models were used to assess bone growth. The first model investigated two unicortical defects in each femora. The second was bone growth in a 500-micron engineered space around one transcortical titanium screw. In the first model there was a significant increase in bone formation at 1 and 2 months in the membrane groups (p < 0.01) as compared to the controls. In the second model the percentage of bone in contact with the implant was significant at 1 and 2 months in the defects covered with membrane compared to the uncovered defects. The uncovered defects had fibrous tissue adherent to the implant continuous with the overlying soft tissue. Our study demonstrated three points: this membrane can be used to increase bone regeneration into defects, this technique allows bone to grow directly around an implant, and butyl-cyanoacrylate can be used in deep soft tissue and bone applications without any apparent deleterious effects.

Animals↗