Bone regeneration using the principle of guided tissue regeneration

The biological principle of "guided tissue regeneration" (GTR) was developed for regenerating periodontal tissues, lost as a result of periodontal disease. This principle was based on the hypothesis that non-desirable types of tissue cells can be prevented from migrating into a wound by means of a membrane barrier and at the same time giving preference to those particular cells to repopulate the wound, which have the capacity to regenerate the desired type of tissue. This principle may have its application in many areas of surgery, aimed at regeneration of lost tissues. One such area is osseous surgery aimed at bone regeneration. In the present paper, a series of experiments in laboratory animals using the method of GTR for regeneration of various types of bone defects are presented as well as examples of application in humans for regeneration of jaw bone defects in conjunction with the placement of dental implants.     

Augmentation of the rat jaw with autogeneic cortico-cancellous bone grafts and guided tissue regeneration

The aim of the present study was to evaluate the effect of augmenting the maxillary alveolar ridge and the lateral aspect of the mandible with onlay autogeneic cortico-cancellous bone grafts that were covered with e-PTFE membranes. The experiment was carried out in 51 rats. In 15 rats, the edentulous maxillary jaw between the incisor and the first molar was augmented by means of an autogeneic ischiac bone graft that was fixed with a gold-coated microimplant. In one side, the graft was covered with an e-PTFE membrane, while the other side, which served as control, was treated without a membrane. In the other 36 rats, the lateral aspect of the mandible was augmented in both sides by means of an autogeneic ischiac bone graft that was fixed with a gold-coated or a titanium microimplant. In one side, the augmented area was covered with an e-PTFE membrane, while the contralateral side was treated without a membrane. Histological analysis at 60, 120 and 180 days after augmentation of the maxilla showed that, in the case of the test sites (where most of the membranes were either exposed or lost), the bone grafts presented extensive resorption and there was a lack of bone continuity between the graft and the recipient site. Similar findings were made at the non-membrane-treated control sides. In the case of augmentation of the mandible with membranes, the bone grafts were not resorbed, but were integrated into newly formed bone at the recipient site. In the control sides, the grafts presented varying degrees of resorption and integration into the recipient bone. It is concluded that, in comparison to bone grafting alone, onlay ischiac bone grafting combined with guided tissue regeneration eliminates the risk of bone graft resorption and ensures integration of the graft into newly formed bone at the recipient site, provided that closure of the operated area can be maintained during healing.     

Osteogenesis by guided tissue regeneration and demineralized bone matrix

AIM: To evaluate in a discriminating capsule model whether bone formation by guided tissue regeneration (GTR) may be influenced by concomitant implantation of demineralized bone matrix (DBM). MATERIALS AND METHODS: Thirty 4-month-old male albino rats of the Wistar strain were used in the study. Following surgical exposure of the mandibular ramus, a hemispherical, Teflon capsule (5.0 mm in diameter), loosely packed with a standardized amount of DBM, was placed with its open part facing the lateral bone surface of the ramus. At the contralateral side, an empty capsule was placed, serving as control. After healing periods of 15, 30, and 120 days, groups of 10 animals were sacrificed and 40-70 microm thick undecalcified sections of the capsules were produced. In the sections, the cross-sectional areas of (1) the space created by the capsule, (2) newly formed bone, (3) DBM particles, (4) loose connective tissue as well as the (5) height of the capsules, and (6) that of the newly formed bone were measured. RESULTS: Increasing bone fill was observed in both test and control sites from 30 to 120 days. After 30 days of healing, the mean amount of bone was approx. 3% of the cross-sectional area of the capsules at the test sites while it was 8% in the control sites (p<0.05). However, no statistically significant differences were observed between the test (46%) and control (64%) sites after 120 days regarding any of the measured parameters (p>0.05). The newly formed bone in the DBM group at 120 days, on the other hand, appeared more dense than that in the control capsules. CONCLUSION: DBM used as an adjunct to GTR did not provide any added effect on bone formation but increased the density of the newly formed bone.     

Long-term stability of jaw bone tuberosities formed by "guided tissue regeneration"

The aim of the present study was to evaluate whether bone tuberosities produced by GTR on the lateral surface of the mandibular ramus in rats are stable on a long-term basis. Thirty male 6-month-old albino rats of the Wistar strain were used in the study. Tissue flaps were elevated on the lateral aspect of the mandibular ramus. The periosteum was preserved (P+) on one side of the jaw while the bone was denuded (P-) on the other. A rigid, non-porous oval-shaped teflon capsule was placed on both sides with its opening facing the ramus. Six months following surgery, 10 rats were sacrificed and prepared for histology while the remaining 20 rats were subjected to a second operation during which the capsules were removed. Standardized radiographs, taken immediately before and after removal of the capsule and after 3, 6, 9 and 12 months, were subjected to planimetric measurements and subtraction radiography. Ten animals were sacrificed and prepared for histological analysis after 6 months following removal of the capsules and the remaining 10 animals after 12 months. Histology revealed that at 6 months after the placement of the capsules, 17 were completely filled with new bone. The remaining 3 capsules which were displaced exhibited only partial bone fill. The radiographic analysis revealed that after 6 months 98.6 +/- 7.6% (mean +/- SD) in average of the cross-sectional area created by the capsules was filled with new bone. Within 3 months after removal of the capsules a slight resorption of the new bone had occurred, thereby reducing the area of the bone tuberosities by 4 to 8%. No further resorption of the bone tuberosities took place from 3 to 12 months. These observations indicating that new bone produced by GTR is stable on a long-term basis, may question the general belief that non-functional bone will resorb over time.     

Treatment of an early implant failure according to the principles of guided tissue regeneration (GTR)

The present case report demonstrates the application of guided tissue regeneration (GTR) in combination with antimicrobial therapy for the treatment of an early implant failure. This treatment approach both prevented further loss of bone as well as led to the regeneration of lost bone. By means of color-converted digital subtraction images, remodelling of the tissues adjacent to the defect was documented as early as one month postsurgically. The images demonstrated "bone-fill" in the apical portion of the defect and resorptive changes at the bone crest. This case report demonstrates that combined regenerative and antimicrobial therapy may be a successful treatment approach restoring osseointegration of dental implants following loss of bone due to infection. Continuously increasing bone-fill inside the defect was documented when comparing the radiograph obtained immediately before the GTR procedure and at months 1, 2, 4, 5 and 6 of the healing period, respectively. Clinical measurement obtained at the time of the surgery and at the time of the membrane removal confirmed the radiographic evidence of bone-fill by demonstrating new tissue resistant to probing in close contact to the implant surface at the site of the previous defect. Antimicrobial therapy included an antibiotic regimen during the 1st month of healing as well as topical rinses with an antiseptic (chlorhexidine) over the entire healing period of 6 months. As a result of this treatment approach, the implant was saved and could be used as an abutment for a bridge reconstruction.     

钛膜引导骨再生在骨内种植体植入中的应用

目的：总结牙种植术后使用钛膜引导骨再生临床体会。方法：对30例47枚牙种植术中发现骨缺损、骨量不足的患者采用钛膜进行骨引导再生修复骨缺损及骨增量。术后定期观察，对新骨生长情况进行连续临床和X线的观察分析。结果：30例47枚牙种植术中，39枚种植体植入部位使用了钛膜。二期手术时种植体均已与骨组织形成理想的骨融合，顺利完成种植义齿修复。39枚种植体中有15枚种植体术后2个月的X线片可见到种植体封闭螺帽上方骨密度增高影。4月后二期手术切开牙龈时可见到新骨覆盖种植体表面，以骨凿等去除新骨后方可见到封闭螺帽。结论：医用钛膜在种植术中应用有较好的引导骨再生作用，有利于种植术后骨融合期新骨的形成。不可吸收性膜的一些固有缺陷可通过临床正确的设计关在术中严格按照操作要点进行手术，可获得理想的骨再生效果。     

Augmentation of the rat mandible using guided tissue regeneration

The aim of the present study was to investigate whether it is possible to increase the height of the rat mandible at its inferior border using a bioresorbable membrane adapted to create a secluded space for ingrowth of bone tissue. The experiment was carried out in 18 rats. The mandibular ramus was exposed at both sides. A standardized titanium microimplant was then inserted in the naturally existing curvature at the inferior border of the mandible, serving as a fixed reference and space maker. The mandibular border on one side was covered with a polyhydroxybutyrate bioresorbable membrane, and the contralateral side, serving as control, received no membrane before closure of the wound. The membranes were placed in such a way that a space was created in the curvature between the membrane and the inferior border of the mandible. Macerated jaw specimens representing 6 months of healing demonstrated substantial amounts of bone formation in the curvature of the inferior border of the mandible, resulting in a flattening of the inferior border. Negligible amounts of bone formation had occurred in the control sides. Histological analysis demonstrated that. in 4 of 6 experimental specimens, the space created by the membrane was completely filled with new bone after 6 months of healing, but in some specimens soft tissue seemed to have migrated into the space through ruptures of the membrane or because of poor membrane adaptation at its lateral borders, thereby inhibiting bone formation. Only negligible bone formation had occurred at the control sides. It can be concluded that augmentation of the mandible can be accomplished using a bioresorbable membrane of polyhydroxybutyrate adapted to create a secluded space for ingrowth of bone tissue. but the membrane must be modified regarding its physical properties before clinical use in maxillofacial surgery.     

GBR技术引导颌骨再生的研究进展

引导骨再生（GBR）是修复种植体周围缺损的重要方法,但在成骨效果上仍有不足。理论上组织工程将生长因子和生物活性材料应用于GBR可以提高疗效,但是目前临床上尚未建立起可预测疗效的种植体周围缺损再生疗法,甚至有研究发现在GBR中使用生长因子后还存在成骨长期稳定性不良的现象,这与理论上预计的结果不符。解决这一问题是推进生长因子应用的关键,通过查阅文献与分析,文中给出了两种可能的原因：生长因子后期水平过低和加速屏障膜降解作用,并据此提出验证的方法,为进一步研究提供参考和依据。     

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.     

Denaturation of demineralized bone matrix significantly reduces bone formation by guided tissue regeneration

AIM: To examine in a discriminating capsule model whether denaturation of demineralized bone matrix (DBM) by heating may influence bone formation. MATERIALS AND METHODS: DBM was produced from the long bones of rats. Half the portion of DBM was denatured by heating in distilled water for 20 min at temperatures between 70 degrees C and 90 degrees C. Prior to the study, the destruction of the osteoinductive properties of the DBM was confirmed in three rats following intramuscular implantation. Thirty, 4-month-old, male albino rats of the Wistar strain were used in the study. Following surgical exposure of the mandibular ramus, a hemispherical Teflon capsule (internal diameter = 5.0 mm) was placed, with its open part facing the lateral aspect of the ramus. On one side (test side), the capsule was loosely packed with denatured DBM, while on the contralateral side, serving as control, the capsule was loosely packed with the same amount of non-denatured DBM. After healing periods of 30, 60, and 120 days, groups of 10 animals were killed and 40-70 microm thick undecalcified sections of the capsules were produced. Three sections from each specimen, representing the mid-portion of the capsule, were subjected to histological analysis and computer-assisted planimetric measurements. RESULTS: Increasing amounts of newly formed bone were observed in both test and control capsules during the experimental period. At 4 months, the new bone formed in the control capsules occupied 46.7% of the cross-sectional area of the capsules, while it was only 19.1% in the test capsules (P<0.05). CONCLUSION: Denaturation of DBM by heating significantly reduces bone formation by guided tissue regeneration.     

引导骨再生技术应用于前牙美学区种植临床效果观察

目的：评价引导骨再生技术在上前牙美学区种植中应用的临床美学效果。方法：单颗前牙种植成功病例29例,其中以引导骨再生种植修复的上前牙二期种植12例为观察组,种植体植入的同时行骨粉充填骨缺损区,再用胶原再生膜覆盖进行骨增量,有效增加牙槽骨的厚度及宽度;另外17例选用未行骨增量常规上前牙二期种植患者为对照组。两组均在术后4—6月暴露种植体完成最终修复,在牙冠戴入当天和种植牙负重6月及12月分别拍摄口内照片、DR全景片,测量和评价二组的PES指数和种植体周围骨水平,比较两组各时间段种植体周围骨水平及软组织红色美学指数统计学差异。结果：所有种植修复负重1年后的临床观察,各个时间段两组问的红色美学指数经检验无统计学差异（P〉O．05）;负重后6～12个月观察组种植体周围骨水平稳定,均位于第一螺纹上方,负重12个月后两组MBL均值差异无显著性（P〉0．05）。结论：引导骨再生种植能获得与正常骨组织种植修复相似临床美学效果。     

Role of chitin beads in the formation of jaw bone by guided tissue regeneration. An experiment in the rat

It has been reported that local application of bone grafts or synthetic bone substitutes (filler materials) may favour bone formation when used in combination with guided tissue regeneration (GTR). Therefore, the aim of the present investigation was to evaluate the effect of application of chitin beads (a bioabsorbable natural polymer) as a bone substitute in bone formation by GTR. The experiment was carried out in 25 rats. The mandibular ramus was exposed on one side after elevation of a muscle-periosteal flap, and a teflon capsule filled with chitin beads (2.0 mm in diameter) was placed with its opening facing the lateral aspect of the ramus. On the contralateral side of the jaw, serving as control, an empty teflon capsule was placed in the same manner. Groups of 5 animals were sacrificed at 7, 15, 30, 60 and 120 days following capsule placement. Histological analysis demonstrated that the amount of newly formed bone was similar in both experimental and control specimens, amounting to approximately 3% of the central/largest, cross-sectional area created by the capsule at 15 days, and to approximately 9% of this area at 30 days following capsule placement. At 60 and 120 days, however, the amount of newly formed bone observed in the control specimens was twice as large as that observed in the test specimens, amounting to approximately 31% of the cross-sectional area created by the capsule at 60 days, and to approximately 45% at 120 days. It is concluded that, although chitin beads (2.0 mm in diameter) are biocompatible, their presence retards bone formation in the model system used.     

冷冻异体骨膜引导即刻种植体周围骨缺损修复的临床研究

目的：观察机体对冷冻异体骨膜的反应及其引导骨组织再生的效果，方法：在实验研究成功的基础上，将冷冻异体骨膜作为引导组织再生膜性材料应用于引导即刻种植义齿植体周围骨缺损的修复。结果：临床观察证实机体对冷冻异体骨膜无排斥反应，膜无脱出，无感染，骨缺损修复率达到92．12％，结论：冷冻异体骨膜是一种理想的引导组织再生膜性材料。     

Vertical ridge augmentation with guided bone regeneration in association with dental implants: an experimental study in dogs

AIM: To evaluate the effect of using guided bone regeneration (GBR) with a titanium-reinforced e-PTFE membrane in alveolar bone defects with titanium implants. MATERIAL AND METHODS: Following extraction of three mandibular premolars and a molar on both sides of the jaw in three dogs, alveolar bone defects (depth: 5-7 mm) were produced. After 4 months, three implants were inserted into each defect to a depth of approximately 4 mm, so that their coronal portion was protruding about 5 mm. Four sides in the dogs were assigned to a test group and the remaining two sides to a control group. The 12 implants in the test group were covered with a reinforced e-PTFE membrane. The space under the membrane was filled with peripheral venous blood from the animal, and the flaps were sutured over the membrane. The six control implants received no membrane before the suturing of the flaps to complete wound closure. The animals were sacrificed after 6 months, and non-decalcified histological specimens of the implants and surrounding tissues were prepared. RESULTS: Histologic and histomorphometric analyses revealed a significantly (Mann-Whitney test; P=0.08) larger amount of bone fill in the test group (mean=57.42%) than in the controls (mean=11.65%), and clinical evaluation of one test site showed that the implants were completely covered with tissue resembling bone. In most of the specimens, bone had grown in height close to, or in direct contact with the membrane. However, the new bone generally was not in direct contact with the implants. Regularly, a zone of dense connective tissue was interposed between the implants and the newly formed bone. CONCLUSION: The formation of even considerable amounts of bone following vertical ridge augmentation with GBR and implants was not accompanied by predictable osseointegration of the implants.     

Guided tissue regeneration ensures osseointegration of dental implants placed into extraction sockets. An experimental study in monkeys.

The aim of the present study was to explore the possibility of achieving osseointegration of dental titanium implants, inserted into alveoli immediately after tooth extraction, by covering the recipient site with a teflon membrane. In each of 7 monkeys, mucoperiosteal flaps were raised on the buccal and palatal aspects of the maxillary molars in both sides of the jaw. The second molars were then extracted and self tapping titanium implants of the screw type (Astra® Dental Implants) were inserted into the sockets of the largest roots. In the coronal portion of the sockets, a void was always present between the implant and the socket walls. In one side of the jaw, a membrane (Gore‐;Tex Aug‐mentation Material@) was adjusted to cover the implant. The implant in the other side of the jaw served as control and was only covered by the tissue flaps. Microscopic analysis after 3 months of healing revealed that soft tissue was facing the coronal portion of the implants to a varying degree in the control side, while osseointegration was consistently observed to the top of the membrane‐covered implants which remained submerged throughout the experimental period. The results suggest that the membrane techniaue can secure complete osseointegration of implants inserted immediately into extraction sockets.     

Marginal bone loss of tissue- or bone-level implants after simultaneous guided bone regeneration in the posterior mandibular region: A retrospective cohort study

The cover image is based on the Original Article Marginal bone loss of tissue- or bone-level implants after simultaneous guided bone regeneration in the posterior mandibular region: A retrospective cohort study by Xiaoting Shen DDS et al., https://doi.org/10.1111/cid.13144 .