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PubMed1994

The role of guided tissue regeneration and guided bone regeneration.

The goal of periodontal therapy includes not only the halting of the progressive loss of connective tissue attachment but also the restitution of those parts of the supporting apparatus which have been destroyed. The cells which repopulate this area may originate from any number of the different tissue components of the periodontium: the dentogingival epithelium, the gingival connective tissue, the alveolar bone, and the periodontal ligament (PDL). The size and shape of the wound and the potential of the different types of tissues cells to migrate, determines the type of healing. Previous studies have revealed that root resorption was found to occur when granulation tissue derived from the gingival connective tissue or alveolar bone was proliferating into contact with the root surface, while re-epithelialization of the surface prevented both connective tissue attachment and root resorption. The only cells which appear to have the capacity to form a new attachment were cells originating from the PDL. Based on this knowledge of the biological behaviour of the different periodontal tissues during wound healing, the principle of Guided Tissue Regeneration (GTR) was introduced and tested. A membrane section was placed over the debrided root surface in such a way that all periodontal tissues except the PDL cells were prevented from reaching contact with the root. Healing resulted in extensive amounts of new connective tissue attachment, that is, the formation of new cementum with inserting collagen fibres. The objective was, and is, assessment of how predictably new attachment may form when treatment included GTR.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Bone Loss↗
PubMed2005

Guided bone regeneration at the donor site of iliac bone grafts for future use as autogenous grafts.

BACKGROUND: Autogenous bone grafting is considered the standard in management of bony defects but has some disadvantages, including limited source of graft material, especially in children. This study represents an attempt to regenerate bone at the donor site of iliac bone grafts using the guided bone regeneration principle for future use in multistage bone reconstruction by grafting. METHODS: Critical size defects were created in 24 iliac bones of 12 skeletally mature New Zealand White rabbits. Defects in group 1 (n = 12) were covered with inverted U-shaped resorbable mesh (space maintainer) and polytetrafluoroethylene membranes underneath the periosteum. In group 2 (n = 6), inverted U-shaped resorbable mesh was used alone (positive control). In group 3 (n = 6), neither resorbable mesh nor polytetrafluoroethylene membranes were used (negative control). An unpaired t test was used for comparison between each two groups. RESULTS: Plain radiographs and contact microradiographic studies showed that bone regeneration was significantly higher in group 1 and group 2 than in group 3 (p < 0.001). There was no significant difference between group 1 and group 2 regarding density. CONCLUSIONS: The periosteum acted as an ideal membrane for guided bone regeneration so that the polytetrafluoroethylene membranes could be used only to compensate for the deficient periosteum. Space maintenance was essential for bone regeneration.

Animals↗
PubMed1999

Guided bone regeneration using demineralized laminar bone sheets versus GTAM membranes in the treatment of implant-associated defects. A clinical and histological study.

This study was designed to compare the regenerative potential at dehisced implant sites of the resorbable demineralized laminar bone sheets and non resorbable GTAM membranes. Twenty-six standard screw-type fixtures showing buccal dehiscences in 7 patients were treated using the GBR principles and received either laminar bone sheets (experimental) or GTAM (control) membranes. Twelve experimental and 10 control sites were available for evaluation at second stage surgery carried out 8 months following implant placement. Height and maximum width of the dehiscence defects were measured at the time of implant insertion and at second-stage procedure. Mean percentage of defect fill was 75.17% in the experimental dehiscences versus 86.70% in the control defects. A statistically significant difference in the percentage of defect fill could not be evidenced between the two treatment modalities. Complete fill was observed in 25% of the experimental versus 70% of the control sites. A significant difference was found in the median Density Index with the GTAM group showing a consistency similar to bone in a larger number of sites. Histologically, material with the same staining features of bone was evidenced inside the GTAM membranes in 3 cases while newly-formed bone was present in all instances under the control GTAM barriers. In the laminar bone-treated sites, the membrane maintained its integrity in almost all cases. Newly formed bone was found underlying the membrane in cases with a Density Index of 5 with no evidence of bony tissue adhering to the laminar sheets.

Absorbable Implants↗
PubMed1993

Platelet-derived growth factor inhibits bone regeneration induced by osteogenin, a bone morphogenetic protein, in rat craniotomy defects.

Platelet-derived growth factor (PDGF) is a potent moderator of soft tissue repair through induction of the inflammatory phase of repair and subsequent enhanced collagen deposition. We examined the effect of recombinant BB homodimer PDGF (rPDGF-BB) applied to rat craniotomy defects, treated with and without bovine osteogenin (OG), to see if bone regeneration would be stimulated. Implants containing 0, 20, 60, or 200 micrograms rPDGF-BB, reconstituted with insoluble rat collagenous bone matrix containing 0, 30, or 150 micrograms OG, were placed into 8-mm craniotomies. After 11 d, 21 of the 144 rats presented subcutaneous masses superior to the defect sites. The masses, comprised of serosanguinous fluid encapsulated by fibrous connective tissue, were larger and occurred more frequently in rats treated with 200 micrograms rPDGF-BB, and were absent in rats not treated with rPDGF-BB. The masses underwent resorption within 28 d after surgery. OG (2-256 micrograms) caused a dose-dependent increase in radiopacity and a marked regeneration of calcified tissue in a dose-dependent fashion within defect sites. However, OG-induced bone regeneration was inhibited 17-53% in the presence of rPDGF-BB. These results suggest that rPDGF-BB inhibited OG-induced bone regeneration and stimulated a soft tissue repair wound phenotype and response.

Animals↗
PubMed1978

[Characteristics of bone regeneration in distraction of bone fragments].

One of the features of distraction osteosynthesis consists in the presence of a zone of permanent growth between bone breaks. Electron microscopic examinations of the permanent growth zone at 14 and 21 days of distraction showed the presence in the zone of cells of three kinds: fibroblast-like cells, osteoblastic elements and little-differentiated preosteoblasts. Fibroblast-like cells and osteoblastic elements were found to have ultrastructural changes of the endoplasmic reticulum indicating the occurrence of intensive synthesizing processes. Specific conditions of blood supply cause hypoxic metabolism with typical enhanced formation of fibrillae which leads to the preservation of the fibrillar tissue throughout the entire period of distraction. The fibrillar tissue in diastace may be considered to be a special growth plate.

Animals↗
PubMed2002

Enhanced guided bone regeneration with a resorbable chamber containing demineralized bone matrix.

BACKGROUND: The effectiveness of a nonporous poly-DL-lactide tubular chamber in guiding bone regeneration through a long bone defect had already been assessed in an experimental model using the rabbit radius. The injection of bone marrow stem cells into the chamber had proven to enhance bone regeneration. METHODS: The present study reports on the development of the above research project in a subsequent stage. Demineralized bone matrix (DBM) obtained by milling New Zealand rabbit femoral and tibial diaphyses was placed into a tubular chamber. A 10-mm defect was bilaterally created in the radii of 10 rabbits. On the left side (chamber side) the defect was treated by means of a poly-DL-lactide chamber filled with DBM, whereas DBM alone was used on the right side (control). RESULTS: Controls were performed at 3 and 6 months by radiographs and histomorphometry and demonstrated better bone growth on the chamber side versus the control side. A comparison with the results previously obtained by stem cell injection into the chamber revealed significant acceleration of bone regrowth in the first 3 months because of the addition of DBM to the chamber. However, no significant difference was found between the two sides after 6 months. CONCLUSION: These results have confirmed the effectiveness of the chamber as a container for the factors promoting bone regeneration, probably because the osteogenetic activity is maintained in situ.

Absorbable Implants↗
PubMed2005

Sonic hedgehog gene-enhanced tissue engineering for bone regeneration.

Improved methods of bone regeneration are needed in the craniofacial rehabilitation of patients with significant bone deficits secondary to tumor resection, congenital deformities, and prior to prosthetic dental reconstruction. In this study, a gene-enhanced tissue-engineering approach was used to assess bone regenerative capacity of Sonic hedgehog (Shh)-transduced gingival fibroblasts, mesenchymal stem cells, and fat-derived cells delivered to rabbit cranial bone defects in an alginate/collagen matrix. Human Shh cDNA isolated from fetal lung tissue was cloned into the replication-incompetent retroviral expression vector LNCX, in which the murine leukemia virus retroviral LTR drives expression of the neomycin-resistance gene. The rat beta-actin enhancer/promoter complex was engineered to drive expression of Shh. Reverse transcriptase-polymerase chain reaction analysis demonstrated that the transduced primary rabbit cell populations expressed Shh RNA. Shh protein secretion was confirmed by enzyme-linked immunosorbent assay (ELISA). Alginate/ type I collagen constructs containing 2 x 10(6) Shh-transduced cells were introduced into male New Zealand White rabbit calvarial defects (8 mm). A total of eight groups (N=6) were examined: unrestored empty defects, matrix alone, matrix plus the three cell populations transduced with both control and Shh expression vectors. The bone regenerative capacity of Shh gene enhanced cells was assessed grossly, radiographically and histologically at 6 and 12 weeks postimplantation. After 6 weeks, new full thickness bone was seen emanating directly from the alginate/collagen matrix in the Shh-transduced groups. Quantitative two-dimensional digital analysis of histological sections confirmed statistically significant (P<0.05) amounts of bone regeneration in all three Shh-enhanced groups compared to controls. Necropsy failed to demonstrate any evidence of treatment-related side effects. This is the first study to demonstrate that Shh delivery to bone defects, in this case through a novel gene-enhanced tissue-engineering approach, results in significant bone regeneration. This encourages further development of the Shh gene-enhanced tissue-engineering approach for bone regeneration.

Adipose Tissue↗
PubMed1992

Short-term effect of guided bone regeneration and electrical stimulation on bone growth in a surgically modelled resorbed dog mandibular ridge.

This study compares the quantitative bone changes that occur in attempting to augment a resorbed mandibular ridge by electrical stimulation and by the guided bone regeneration technique. At the base line three defects resembling an atrophic ridge were created in the mandible of 5 beagle dogs. Concomitantly, a constant current generator producing 20 +/- 2 mA was implanted under the floor of the mouth. Six weeks later a titanium cathode was inserted in the first bony defect and connected to the generator (electrical stimulation = ES); another titanium cathode, not connected to the generator, was inserted in the second defect (non-electrical stimulation = non-ES); the third defect remained without an electrical device (membrane only = MO). All 3 defects were covered with an expanded polytetrafluorethylene membrane, so as to prevent soft tissue proliferation into the defects. Tetracycline bone labelling compounds were administered to mark new bone formation. Four weeks following stimulation, ground sections were prepared for fluorescent microscopy. Differences between ES vs MO and between non-ES vs MO mean scores were statistically significant, indicating that 4 weeks of electrical stimulation resulted in similar bone formation as with non- electrical stimulation when both are confined to a membrane isolated defects.

Animals↗
PubMed1999

Temporal and spatial characterization of regenerate bone in the lengthened rabbit tibia.

A rabbit model of bilateral tibial lengthening was used to investigate temporal and spatial changes in new bone volume and architecture during regenerate bone formation. Tibiae were lengthened 9.0 mm at 0.75 mm/day after a 6-day latency period. Animals were euthanized at four time points, and new bone volume and architecture within the distraction gap were assessed by microcomputed tomography and histomorphometry. New bone formation began before day 18 postsurgery and increased markedly between day 18 (completion of distraction) and day 24. This period of high bone formation activity might therefore be optimal for biologic and mechanical interventions aimed at enhancing bone regeneration. Regions of both endochondral and intramembranous bone formation were observed throughout the consolidation period. Significant increases in bone volume fraction were observed early in the consolidation period and were attributed to significant increases in trabecular thickness. This suggested that increased mineral density in the gap tissue with time was a consequence of increased osteoblast activity and associated trabecular thickening. New bone formation was shown to be highly oriented toward the distraction axis throughout lengthening. More bone formed consistently in lateral and proximal regions of the distraction gap, perhaps due to improved blood supply or progenitor cell availability in these areas. No differences in trabecular architecture were detected between regions having more or less bone volume, suggesting that bony tissue differentiation in all regions of the distraction gap was similar. Homotypical variations in measures of bone architecture were small; thus, these outcome variables seem appropriate for determining the effects of biological and mechanical interventions on bone regeneration in this animal model.

Animals↗
PubMed1997

Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced bone regeneration and osseointegration was evaluated in supraalveolar peri-implant defects in 5 beagle dogs. Alveolar bone was reduced 5 mm in height in mandibular premolar areas and the premolars were extracted. Three 10 mm titanium fixtures were placed 5 mm into each reduced alveolar crest, leaving 5 mm in a supraalveolar position. Alternate quadrants in consecutive animals received a surgical implant consisting of 2 ml rhBMP-2 (0.43 mg/ml) in a type I bovine collagen carrier, or the carrier alone (control). Fixtures and surgical implants were submerged under the gingival flaps. The healing interval was 16 weeks. Histometric and radiographic evaluations were made. Defect height averaged (+/- SD) 5.3 +/- 0.2 and 5.1 +/- 0.2 mm for rhBMP-2 and control defects, respectively (P > 0.05, n = 5, paired, t-test) Bone regeneration (height) averaged 4.2 +/- 1.0 and 0.5 +/- 0.3 mm for rhBMP-2 and control defects, respectively (P < 0.05). Bone regeneration (area) averaged 6.1 +/- 6.3 and 0.2 +/- 0.2 mm2 for rhBMP-2 and control defects, respectively (P > 0.05). Osseointegration within the confines of the defect averaged 19.1 +/- 10.1% and 8.2 +/- 4.6% for rhBMP-2 and control defects, respectively (P > 0.05). Osseointegration within regenerated bone averaged 29.1 +/- 9.8% and 65.3 +/- 15.3% for rhBMP-2 and control defects, respectively (P < 0.05). Osseointegration within the retained alveolar bone averaged 67.1 +/- 4.6% and 68.1 +/- 3.6% for rhBMP-2 and control defects, respectively (P > 0.05). The results suggest that there is a potential for rhBMP-2 induced bone regeneration and osseointegration in surgical peri-implant defects.

Alveolar Process↗
PubMed2005

Bone regeneration in the rat mandible with bone morphogenetic protein-2: a comparison of two carriers.

OBJECTIVE: To compare mandibular bone regeneration with bone morphogenetic protein-2 (BMP-2) delivered with two carriers: a hyaluronic acid polymer (HY), and a collagen carrier complexed with calcium hydroxyapatite and tricalcium phosphate (collagen/HA/TCP). STUDY DESIGN: Defects were created in the bilateral mandibular bodies of 16 Sprague-Dawley rats. The defects were filled with the HY carrier, the HY carrier loaded with BMP-2, the collagen/HA/TCP carrier, or the collagen/HA/TCP carrier loaded with BMP-2. Animals were euthanatized after 6 weeks, and the hemi-mandibles were analyzed histomorphologically. RESULTS: Specimens containing BMP-2 had significantly larger new bone and marrow volumes than control specimens. Specimens in the hyaluronan/BMP-2 group tended to have larger volumes of new bone and osteoid than collagen/HA/TCP/BMP-2 specimens, though these differences were not statistically significant. CONCLUSION: The HY and collagen/HA/TCP carriers had comparable efficacy for bone healing with BMP-2. SIGNIFICANCE: Bone morphogenetic proteins can be delivered with commercially available alloplasts as osteogenic bone substitutes for the repair of craniofacial bone defects. EBM RATING: B-2.

Animals↗
PubMed2005

Effect of transforming growth factor-beta1 on bone regeneration in critical-sized bone defects after irradiation of host tissues.

OBJECTIVE: To determine whether sustained release of transforming growth factor (TGF)-beta1 from a gelatin hydrogel would enhance bone regeneration in critical-sized long-bone defects and overcome inhibitory effects of preoperative irradiation. ANIMALS: 24 adult New Zealand White rabbits. PROCEDURE: Rabbits were allocated to 2 groups. Twelve rabbits received localized megavoltage radiation to the right ulna by use of a cobalt 60 teletherapy unit, and 12 rabbits received no irradiation. Then, a 1.5-cm defect was aseptically created in the right ulna of each rabbit. Gelatin hydrogel that contained 5 microg of adsorbed recombinant-human (rh)TGF-beta1 was placed in the defect of 12 rabbits (6 irradiated and 6 nonirradiated), and the other 12 rabbits received hydrogel without rhTGF-beta1. Rabbits were euthanatized 10 weeks after surgery. New bone formation within the defect was analyzed by use of nondecalcified histomorphometric methods. A 1-way ANOVA was used to compare differences among groups. RESULTS: New bone formation within the defect was significantly greater in TGF-beta1-treated rabbits than in rabbits treated with hydrogel carrier alone. Local delivery of rhTGF-beta1 via a hydrogel carrier in irradiated defects resulted in amounts of bone formation similar to those for nonirradiated defects treated by use of rhTGF-beta1. CONCLUSIONS AND CLINICAL RELEVANCE: Local delivery of TGF-beta1 by use of a hydrogel carrier appears to have therapeutic potential for enhancing bone formation in animals after radiation treatments. IMPACT FOR HUMAN MEDICINE: This technique may be of value for treating human patients at risk for delayed bone healing because of prior radiation therapy.

Administration, Topical↗
PubMed1997

Guided bone regeneration: integration of a resorbable membrane and a bone graft material.

Guided bone regeneration relies primarily on four principles--exclusion of unwanted tissues and cells, space creation and maintenance, protection of the underlying blood clot, and wound stabilization. For successful bone regeneration to occur, large bony defects require an underlying grafting material and a cell-occlusive membrane. The learning objective of this article is to review the history and principles of guided bone regeneration and describe the characteristics of a slowly resorbing bilayer collagen membrane, well suited for bone regeneration procedures. An osteoconductive bone grafting material and its ability to support the overlying collagen membrane and serve as a matrix for the ingrowth of vascular and bone-forming cells are discussed.

Absorbable Implants↗
PubMed2000

Contribution of the periosteum to bone formation in guided bone regeneration. A study in monkeys.

The periosteum has been referred to as a protective barrier in the regeneration of bone defects. The objective of this study was to determine the contribution of periosteum as a natural barrier to bone formation in guided bone regeneration. Mucoperiosteal flaps were elevated bilaterally on the buccal aspect of the mandibular angle in 5 cynomolgus monkeys. Bleeding was induced by perforating the cortical bone. A hemispherical titanium mesh was fixed over the areas thus creating a void 5 mm in height between the mesh and the bone surface. One one side the mesh was covered with an ePTFE membrane (test side). The contralateral side did not receive further treatment (control side). After 4 month healing, histomorphometric analyses were used to determine the percentage of new bone in the void underneath the mesh, and the ratio between mineralized tissue and marrow spaces in new and old bone. The mean percentage of new bone tissue was 77.2 +/- 7.5% for the test sides and 68.6 +/- 8.4% for the control sides (P = 0.018, t-test). This new bone contained 80.0 +/- 3.6% mineralized tissue in the test group and 82.5 +/- 5.0% in the control group (P > 0.05, t-test). In both groups the newly formed bone exhibited significantly less mineralized tissue than the old bone (P < 0.05, t-test). It is concluded from this study that new bone formation was enhanced by the additional use of an ePTFE membrane under a periosteum-lined mucoperiosteal flap when space maintenance was excluded as a critical factor.

Animals↗
PubMed2003

Use of isolated mature osteoblasts in abundance acts as desired-shaped bone regeneration in combination with a modified poly-DL-lactic-co-glycolic acid (PLGA)-collagen sponge.

Controlled regeneration of bone or cartilage has recently begun to facilitate a host of novel clinical treatments. An osteoblast line, which we isolated is able to form new bone matrix in vivo within 2 days and exhibits a mature osteoblast phenotype both in vitro and in vivo. Using these cells, we show that cuboidal bones can be generated into a predesigned shaped-bone with high-density bone trabeculae when used in combination with a modified poly-DL-lactic-co-glycolic acid (PLGA)-collagen sponge. PLGA coated with collagen gel serves as a good scaffold for osteoblasts. These results indicate that mature osteoblasts, in combination with a scaffold such as PLGA-collagen sponge, show promise for use in a custom-shaped bone regeneration tool for both basic research into osteogenesis and for development of therapeutic applications.

Absorbable Implants↗
PubMed2005

Guided bone regeneration to repair an alveolar bone defect in a girl whose cleft lip and palate had been repaired.

We report the case of a girl aged 10 years whose alveolar bony defect was closed with a polytetrafluoroethylene membrane, which was incorporated in bone after 4 months. We suggest that the principle of guided bone regeneration can be used to repair cleft defects provided that the mucoperiosteal flaps are handled carefully and that good anti-infective measures are taken to prevent early exposure and microbial contamination of the membrane barrier.

Alveolar Process↗