Periodontal repair in dogs: guided tissue regeneration enhances bone formation in sites implanted with a coral-derived calcium carbonate biomaterial

BACKGROUND: Previous studies suggest that a bioresorbable calcium carbonate coral implant (CI) supports space provision and bone formation for guided tissue regeneration (GTR). However, it could not be discerned whether observed effects were because of GTR or whether the CI possessed osteoconductive properties enhancing bone formation. The objective of this study was to evaluate bone formation associated with the CI biomaterial in the presence and absence of provisions for GTR. METHODS: Routine, critical size, 6 mm, supra-alveolar periodontal defects were created in 12 young adult Beagle dogs. Five animals received the CI alone (Biocoral 1000). Seven animals received the CI/GTR combination using an expanded polytetrafluoroethylene barrier (GORE-TEX Regenerative Material). The animals were euthanized at 4 weeks postsurgery and tissue blocks of the experimental sites were collected and processed for histometric analysis. RESULTS: Clinical healing was uneventful. The histopathologic and histometric analysis revealed significantly increased bone formation (height and area) in sites receiving the CI/GTR combination compared with CI alone (2.3+/-0.6 versus 1.2+/-0.9 mm; and 3.1+/-0.8 versus 1.2+/-1.1 mm2; p<0.05). The CI biomaterial appeared to be mostly unassociated with new bone formation; the CI particles were observed sequestered in newly formed bone, fibrovascular marrow, and in the supra-alveolar connective tissue. Cementum formation was limited and observed in few sites for both treatment protocols. CONCLUSION: While GTR promoted new bone formation, the CI contributed limited, if any, osteoconductive effects.     

Local delivery of prostaglandin E1 induces periodontal regeneration in adult dogs

Formation of cementum, alveolar bone and periodontal ligament was produced in 18 sites on buccal surfaces of mandibular premolars and molars of 11 adult dogs near to sites of local delivery of prostaglandin E₁ (PGE) for three weeks. Mineralizing bone and cementum were labelled with fluorescent dyes and polarizing microscopy showed periodontal ligament fibers between these new mineralized tissues. These observations extend recent demonstrations that local application of PGE causes formation of new bone on the mandible and suggest the potential for predictable, site-directed periodontal regeneration.     

Periodontal repair in dogs: effect of recombinant human transfornning growth factor-β1 on guided tissue regeneration

Abstract. This study evaluated alveolar bone and cementum regeneration following surgical implantation of recombinant human transforming growth factor- β₁ (rhTGF-β₁) in conjunction with guided tissue regeneration (GTR). Supraalvcolar, critical size, periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in right and left jaw quadrants in 5 beagle dogs. Alternate jaw quadrants in consecutive animals received rhTGF-β₁ in a CaCO₃/ hydroxyethyl starch carrier with GTR, or carrier with GTR alone (control), 20μg of rhTGF-/A in buffer solution was incorporated into approximately 0.8 ml of carrier for each defect scheduled to receive rhTGF-β₁. Animals were sacrificed at week 4 postsurgery and tissue blocks were harvested and processed for histo-metric analysis. Clinical healing was generally uneventful. Minor membrane exposures were observed. Defects with membrane exposure displayed an inflammatory infiltrate underneath the membrane. Bone regeneration of trabecular nature, apparent in all animals, was generally limited to the very apical aspect of the defects. Cementum regeneration was limited without obvious differences between experimental conditions. Comparing rhTGF-β to control defects, statistically significant differences were found for area (1.8±0.4 and 1.3±0.6 mm², respectively: p<0.05) and density (0.3±0.1 and 0.2±0.03. respectively: p<0.05) of alveolar bone regeneration. Observed differences are small and represent a clinically insignificant potential for enhanced regeneration in this preclinieal model. Within the limitations of study, it may be concluded that rhTGF-β₁ has a restricted potential to enhance alveolar bone regeneration in conjunction with GTR.     

Periodontal repair in dogs: rhBMP-2 significantly enhances bone formation under provisions for guided tissue regeneration

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to support the regeneration of alveolar bone and periodontal attachment in surgically created periodontal defects and in defects with a history of dental plaque and calculus exposure. Periodontal regeneration has also been shown following guided tissue regeneration using space-providing expanded polytetrafluoroethylene (ePTFE) devices. The objective of this study was to evaluate the influence of rhBMP-2 on regeneration of alveolar bone and periodontal attachment used in conjunction with a space-providing ePTFE device. METHODS: Routine, critical-size, 5-6 mm, supra-alveolar, periodontal defects were created around the third and fourth mandibular premolar teeth in four young adult Hound Labrador mongrel dogs. rhBMP-2 (0.2 mg/ml) in an absorbable collagen sponge (rhBMP-2/ACS) or buffer/ACS (control) implants were randomly assigned to be placed around the premolar teeth in the left and right jaw quadrants in subsequent animals. Space-providing ePTFE devices with 300-microm laser-drilled pores, 0.8 mm apart, were used to cover the rhBMP-2 and control implants. The gingival flaps were advanced for primary wound closure. The animals were euthanized at 8 weeks postsurgery for histologic and histometric analyses. RESULTS: Bone regeneration and ankylosis were significantly increased in jaw quadrants receiving rhBMP-2/ACS compared to control (bone height 4.8+/-0.3 versus 2.0+/-0.2 mm, p=0.001; bone area 10.9+/-1.3 versus 1.4+/-0.1 mm2; p=0.009, and ankylosis 2.2+/-0.2 versus 0.04+/-0.7 mm; p=0.01). No differences between groups were found for cementum regeneration and root resorption. CONCLUSIONS: rhBMP-2 significantly enhances regeneration of alveolar bone in conjunction with a space-providing, macroporous ePTFE device for GTR.     

Histopathological observations of a polylactic acid-based device intended for guided bone/tissue regeneration

Background: Barrier devices have been shown to support alveolar bone and periodontal regeneration, a procedure also known as guided bone/tissue regeneration (GBR/GTR). Popular demand and clinical convenience have raised an interest in bioresorbable barrier devices. Tissue reactions to such bioresorbable devices are, however, generally not well explored. Purpose: The objective of this study was to evaluate short‐ and long‐term tissue reactions following implantation of a bioresorbable polylactic acid (PLA)‐based barrier device using a rat model. Materials and Methods: Twenty‐one young adult male Sprague‐Dawley rats were used. The animals were divided into three groups including 15 animals receiving the PLA device and animals serving as sham surgery (five) or nonoperated (one) controls. Using aseptic techniques, the PLA device was surgically implanted in direct contact with the calvarial bone. Animals receiving the PLA device were sacrificed at 3, 5, 7, and 12 months postsurgery to provide longitudinal histopathological observations of tissue and biomaterials reactions. Control animals were sacrificed at 3 months. Results: Animals were maintained without adverse events. Sham surgery and nonoperated control animals showed no signs of new bone formation or resorption, or signs of inflammatory reactions in adjoining soft tissues. In contrast, extensive amounts of residual biomaterial with evidence of foreign body reactions and bone resorption were observed in animals receiving the PLA device over 12 months. Conclusions: The results suggest that the PLA device may induce bone resorbing foreign body reactions. Importantly, the PLA device does not resorb within a 12‐month healing interval. These biomaterials properties may influence new bone formation and maintenance when applying the device for GBR/GTR.     

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提要：牙槽突裂二期植骨术后,移植骨的再吸收是常见并发症,骨量的不足也为其后的序列治疗带来困难。怎样减少或避免移植骨的再吸收是目前牙槽突裂修复的研究热点之一。近年来,许多学者将引导组织再生技术应用于牙槽突裂修复中,包括将引导组织再生膜应用于二期骨移植中,评价其在减少骨再吸收方面的作用;以及单独应用引导组织再生膜修复牙槽突裂,评价其不通过骨移植修复牙槽骨缺损的效果及可行性;同时进行对比研究,并讨论了如何选择引导组织再生膜。本文就近年来利用引导组织再生技术修复牙槽突裂的研究情况综述如下。     

Enamel matrix derivative versus guided tissue regeneration in the presence of nicotine: a histomorphometric study in dogs

AIM: The goal of this histometric study was to compare the healing process of dehiscence-type defects treated by enamel matrix derivative (EMD) or guided tissue regeneration (GTR) under the effect of nicotine in the dog model. MATERIALS AND METHODS: Eight mongrel dogs were used. Buccal osseous dehiscences were surgically created on the mesial roots of the mandibular third and fourth pre-molars. The defects were exposed to plaque accumulation for 3 months. After this period, the defects were randomly assigned to one of the treatments: open flap debridement (OFD), EMD or GTR with a resorbable membrane. During 4 months, the dogs received subcutaneous administration of nicotine (2 mg/kg twice a day with a 12 h interval between the applications). After this period, the animals were killed and the blocks were processed. The histometric parameters evaluated included gingival recession, epithelial length, connective tissue adaptation, new cementum and new bone. RESULTS: A superior length of new cementum was observed in the sites treated by EMD in comparison with OFD (p< or =0.05). No statistically significant differences were observed between GTR and the other groups. CONCLUSIONS: In the presence of nicotine, EMD may promote more new cementum formation than OFD while GTR failed to provide a significant difference.     

Collagen gel and membrane in guided tissue regeneration in periodontal fenestration defects in dogs

Abstract The effect of a collagen gel matrix as a submembranous space-maintaining material was evaluated in guided tissue regeneration procedures. In 4 dogs, contralateral surgical circular fenestration defects, 5 mm in diameter, were produced at the midbuccal aspect of the alveolar bone in 8 maxillary canines. Removal of bone, PDL and cementum was complete. Experimental sites were filled with collagen gel and covered with collagen membranes; control sites were covered with collagen membranes and the underlying space was spontaneously filled with blood. Mucogingival flaps were repositioned. Histological and histomorphometric observations, 6 weeks post-surgery, indicated that defects covered by collagen membranes presented the most impressive regeneration with almost complete coverage of the denuded root by new cementum (98.4%) and new bone (63.2%). In the experimental defects. 83.5% coverage of new cementum with only 21.9% new bone regeneration was observed. These results suggest that collagen gel. interfered with healing by PDL and bone-derived cells in the submembranous space.     

Prognostic factors for alveolar regeneration: effect of tissue occlusion on alveolar bone regeneration with guided tissue regeneration

OBJECTIVES: Design criteria for guided tissue regeneration (GTR) devices include biocompatibility, cell occlusion, space-provision, tissue integration, and ease of use. The objective of this study was to evaluate the effect of cell occlusion and space-provision on alveolar bone regeneration in conjunction with GTR. METHODS: Routine, critical-size, 6 mm, supra-alveolar, periodontal defects were created in 6 young adult Beagle dogs. Space-providing ePTFE devices, with or without 300-microm laser-drilled pores were implanted to provide for GTR. Treatments were alternated between left and right jaw quadrants in subsequent animals. The gingival flaps were advanced for primary intention healing. The animals were euthanized at week 8 post surgery. The histometric analysis assessed regeneration of alveolar bone relative to space-provision by the ePTFE device. RESULTS: A significant relationship was observed between bone regeneration and space-provision for defect sites receiving the occlusive (beta = 0.194; p < 0.02) and porous (beta = 0.229; p < 0.0004) GTR devices irrespective of treatment (p = 0.14). The bivariate analysis showed that both space-provision and device occlusivity significantly enhanced bone regeneration. Hence, sites receiving the occlusive GTR device and sites with enhanced space-provision showed significantly greater bone regeneration compared to sites receiving the porous GTR device (p = 0.03) or more limited space-provision (p = 0.0002). CONCLUSIONS: Cell occlusion and space-provision may significantly influence the magnitude of alveolar bone regeneration in conjunction with guided tissue regeneration.     

Evaluation of guided tissue regeneration in interproximal defects

Abstract This study clinically evaluates the use of expanded polytetrafluoroethylene (ePTFE) membranes with or without the addition of decalcified freeze-dried hone allograft (DFDBA) in the treatment of interproximal intraosseous defects, 25 patients (26 paired defects) diagnosed with advanced periodontitis and having at least 2 bilateral interproximal probing depths of s6 mm participated in the study. After the hygiene phase, measurements were made to determine soft tissue recession, pocket depth, and clinical attachment levels. Defects from each pair were randomly treated with either ePTFE alone (control), or ePTFE + DFDBA (experimental). Measurements were made during the surgery to determine crestal resorption, defect resolution and defect fill. Membranes were removed at 4 to 6 weeks. At 6 months, the soft and hard tissue measurements (surgical reentry) were repeated. Both groups showed statistically significant improvement when compared to baseline (p<0.001), but no difference was determined between groups. Control sites showed a 50% bone fill and experimental sites had 54% bone fill. The defect resolution changes were also similar between control and experimental groups, respectively (80%, 74%). For this short-term study, it was concluded that either technique was beneficial for the treatment of intraosseous defects. Other studies are needed to assess the long-term stability of the improvements rendered by these treatments.     

The use of guided tissue regeneration techniques among endodontists: a web-based survey

Introduction

The purpose of this study was to determine factors and clinical situations that influence an endodontist’s decision to use guided tissue regeneration (GTR) techniques during endodontic root-end surgery.

Methods

An invitation to participate in a web-based survey was e-mailed to 3,750 members of the American Association of Endodontists. Data were collected from 1,129 participants, representing a 30.1% completion rate. The number of questions varied from 3 to 11 depending on individual responses.

Results

40.7% of respondents who perform root-end surgeries also use GTR techniques. The clinical situation in which GTR techniques are used most often is for transosseous lesions. Barrier membranes and bone replacement grafts are each used by more than 85% of respondents using GTR techniques. Insufficient training and insufficient evidence in support of its use were selected as the predominant reasons for not using GTR techniques at 42.4% and 32%, respectively.

Conclusions

Although over 40% of respondents are currently using GTR techniques in conjunction with their root-end surgeries, a majority of those who do not use GTR indicated they would consider using these techniques with better evidence and available training.     

引导组织再生术诱导兔下颌骨正中缝骨融合的研究

目的观察引导组织再生术诱导发育性骨裂隙骨再生融合的作用,为引导组织再生术在唇腭裂骨性裂隙修复中的应用提供实验依据。方法将国产聚四氟乙烯膜盖于兔下颌骨正中缝唇舌两侧,通过放射和病理检查,观察骨缝融合的情况。结果引导组织再生术能在4周左右诱导骨裂隙完全骨融合。结论引导组织再生术是修复骨性裂隙的有效方法,有可能用于齿槽裂、跨裂的骨性修复。     

New attachment and bone formation in periodontal defects following treatment of submerged roots with guided tissue regeneration

Abstract The purpose of the present study was to examine the effect on periodontal regeneration of preventing bacterial contamination of the membrane material following the guided tissue regeneration procedure (GTR). Periodontal dehiscence defects were surgically produced in 2 monkeys. In each monkey, 8 of these defects were submerged after resection of the crowns of the teeth and a teflon (Gore-Tex Periodontal Material®) or a polyglactin (Vicryl Mesh®) membrane was adjusted to cover the defect and the exposed root surface. 4 defects on non-crown resected teeth were treated with either a teflon or a polyglactin membrane positioned with the coronal border approximately 2 mm below the margin of the covering tissue flap. Following 6 months of healing, the animals were sacrificed. Histological evaluation of the specimens revealed that roots which were kept completely covered during the healing period demonstrated new connective tissue attachment and bone formation corresponding to 67–100% of the length of the initial defect depth, whereas the amount of new connective tissue attachment and bone on non-submerged roots ranged between 30–59% and 11–31%, respectively. It seems reasonable to anticipate that it is bacterial contamination of the membrane material which jeopardizes the formation of new connective tissue attachment but in particular bone formation following the GTR-procedure.     

The use of irradiated-crosslinked human collagen membrane in guided tissue regeneration.

Irradiated glutaraldehyde-crosslinked human collagen membrane was evaluated for its effects on new attachment formation in clinical trials, using the principle of guided tissue regeneration (GTR). 19 adult periodontitis patients with 52 matched bilateral periodontal defects received scaling and polishing with oral hygiene instruction. The bilateral periodontal defects were treated by reflecting a flap with collagen membrane (test) or flap reflection alone (control). Plaque (P1I) and gingival index (GI) scorings, probing pocket depth (PPD) and probing attachment level (PAL) along with classification of furcation involvement (FI) and bony defects were made at pre- and post surgery (6 weeks, 3 and 6 months). Improvement of P1I and GI scores was seen in both test and control sites following the surgical therapy. Reductions in PPD and PAL were significantly (p less than 0.001) more pronounced at 6 months in the test sites compared to the controls. The 2 Class I furcations in the graft-treated teeth showed complete resolution, while the corresponding furcations in the control teeth showed incomplete closure. The use of human collagen membrane based on the GTR technique for treatment of human periodontal defects provided greater gain of clinical attachment than when flap surgery alone was undertaken.     

Prognostic factors for alveolar regeneration: effect of a space-providing biomaterial on guided tissue regeneration

OBJECTIVES: There is a limited understanding of the effect of bone biomaterials on the healing potential when used in conjunction with guided tissue regeneration (GTR). The objective of this study was to evaluate the effect of a space-providing coral-derived biomaterial on alveolar bone regeneration in conjunction with GTR. METHODS: Bilateral, critical-size, 6-mm, supra-alveolar, periodontal defects were created in four young adult Beagle dogs. In a split-mouth design, the animals received an ePTFE device to provide for GTR in contralateral defect sites with or without the coral biomaterial. The animals were euthanized at 4 weeks post surgery. A histometric analysis assessed vertical regeneration of alveolar bone relative to space-provision by the ePTFE device. Because of the correlation of within-dog measurements, a mixed model ANOVA was used to analyze the data. RESULTS: There was significantly greater mean bone regeneration in sites receiving calcium carbonate coral implant GTR (cGTR) compared to GTR (p < 0.0001). Sites providing larger wound areas exhibited greater bone regeneration compared to sites exhibiting smaller wound areas (p < 0.0001). However, grouping the sites by wound area thresholds showed that bone regeneration was not significantly different in sites receiving cGTR compared to sites receiving GTR alone, irrespective of the size of the wound area (p > 0.5). Conclusions: Space-provision has a significant effect on bone regeneration following GTR. The coral biomaterial effectively enhances space-provision, and this appears to be the principal mechanism by which this biomaterial supports bone regeneration rather than postulated osteoconductive properties.     

Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs

Objectives: The aim of the present study was to compare a newly developed biodegradable polylactide/polyglycolide/N‐methyl‐2‐pyrrolidone (PLGA/NMP) membrane with a standard resorbable collagen membrane (RCM) in combination with and without the use of a bone substitute material (deproteinized bovine bone mineral [DBBM]) looking at the proposed tenting effect and bone regeneration. Materials and methods: In five adult German sheepdogs, the mandibular premolars P2, P3, P4, and the molar M1 were bilaterally extracted creating two bony defects on each site. A total of 20 dental implants were inserted and allocated to four different treatment modalities within each dog: PLGA/NMP membrane only (Test 1), PLGA/NMP membrane with DBBM (Test 2), RCM only (negative control), and RCM with DBBM (positive control). A histomorphometric analysis was performed 12 weeks after implantation. For statistical analysis, a Friedman test and subsequently a Wilcoxon signed ranks test were applied. Results: In four out of five PLGA/NMP membrane‐treated defects, the membranes had broken into pieces without the support of DBBM. This led to a worse outcome than in the RCM group. In combination with DBBM, both membranes revealed similar amounts of area of bone regeneration and bone‐to‐implant contact without significant differences. On the level of the third implant thread, the PLGA/NMP membrane induced more horizontal bone formation beyond the graft than the RCM. Conclusion: The newly developed PLGA/NMP membrane performs equally well as the RCM when applied in combination with DBBM. Without bone substitute material, the PLGA/NMP membrane performed worse than the RCM in challenging defects, and therefore, a combination with a bone substitute material is recommended. To cite this article:
Jung RE, Kokovic V, Jurisic M, Yaman D, Subramani K, Weber FE. Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs.
Clin. Oral Impl. Res. 22 , 2011; 802–807
doi: 10.1111/j.1600‐0501.2010.02068.x     

Formation of jawbone tuberosities by guided tissue regeneration. An experimental study in the rat.

The aim of this study was to explore the possibility of creating bone tuberosities on the mandibular ramus in rats, using a rigid, occlusive. Teflon capsule. The experiment was carried out in 30 rats. The mandibular ramus was exposed bilaterally. On the test side, the periosteum was left covering the lateral surface of the ramus. On the contralateral side (control). the periosteum was elevated from the lateral surface together with the flap. A hemispherical, Teflon capsule was then placed to face the periosteum or the bone surface with its open part before closure of the wound. The healing periods comprised 7–120 days. Histological analysis demonstrated increasing bone fill in the test specimens from 7 to 60 days, and a limited further increase was observed from 60 to 120 days. In the control specimens, limited bone fill was seen within the first month after surgery, but substantial amounts of new bone were produced from 30–120 days. At 120 days, the mean amount of bone obtained in the test specimens was 56%(range 39%‐71%) of the total space created by the capsules, and it was 52%(range 32%‐85%) in the controls. The amount of newly formed bone was equivalent to a 5–6 times increase of the original width of the mandibular ramus. These findings indicate that a secluded space created by an occlusive barrier adjacent to existing bone or periosteum may be filled out with bone tissue. This may have a great clinical impact in cranial and maxillofacial surgery.     

生长因子复合生物膜引导牙周组织再生

随着引导组织再生术(guided tissue regeneration，GTR)研究的不断深入，传统的生物膜已经逐渐被复合生长因子的功能性生物膜所替代。功能性复合膜的研制、开发和应用，已成为GTR研究的热点，越来越多的研究表明生长因子缓释生物膜将是未来GTR研究的趋势。     

Treatment of 3rd molar-induced periodontal defects with guided tissue regeneration

Abstract Recent reports provide evidence of increased attachment levels when using guided tissue regeneration (GTR) techniques for the treatment of periodontal defects. Periodontal defects frequently occur at the distal aspect of mandibular 2nd molars which are next to mesioangular impacted 3rd molars that have oral communication. The purpose of this study was to determine whether the use of GTR can enhance probing attachment levels (PALs) following extraction of mesioangular impacted third molars. 12 patients with bilateral soft tissue impacted mandibular 3rd molars entered this split mouth study. After extractions, the previously exposed distal root surface of the 2nd molars were debrided. The defects on the randomly selected experimental sites were covered with expanded polytetraflouro-ethylene (e-PTFE) membrane and the tissue was replaced to cover the membrane. Membranes were removed after 6 weeks. Control sites were treated identically except no membrane was placed. GI, PII, PD, PAL and BOP records were obtained at 0, 3 and 6 months. The use of barrier material did not provide statistically-significant differences in PAL when comparing experimental versus control sites. Nevertheless, PAL gain was consistently greater at 3 and 6 months when GTR techniques were used in sites with deep impactions.     

Periodontal repair or regeneration: structures of different types of new attachment

The present study details the structural and ultrastructural features of healing events between the regenerated periodontal ligament and the root surface after experimental periodontal disease. Experiments were performed on dogs, and the concept of guided tissue regeneration was tested using resorbable polyurethane membranes. Light microscopy, scanning- and transmission electron microscopy were employed to determine if healing events involve regeneration (ie, process by which the architecture and the function are completely renewed) or periodontal repair (ie, healing of a wound by tissue that does not fully restore the architecture of a part). Regeneration occurred in parts of the roots only if some original cementum remained on the root surface after root planing. Repair was observed if peripheral dentin was removed by root planing as this layer was not reestablished. In areas remote from the base of the defect, new collagen fibrils, synthesized by fibroblasts and oriented perpendicular to the root surface, were spliced with severed ends of Sharpey's fiber bundles of original cementum. If circumpulpal dentin was exposed, intermingling between new fibrils with dentinal matrix fibrils occurred. In areas near the base of the defect, the first event was the formation of a cementoid by a cementoblast monolayer and subsequent formation of intrinsic fibrils oriented parallel to the root surface. Afterwards, the cementoblast monolayer disintegrated and extrinsic fiber bundles became anchored in the new cellular mixed fiber cementum. In these areas, linkage between new cementum and pre-existing tissues always occurred by interfacial intermingling of the fibrils, regardless of whether new attachment occurred at circumpulpal dentin or original cementum.