Extracellular matrix expression and periodontal wound-healing dynamics following guided tissue regeneration therapy in canine furcation defects

AIM: Temporal and spatial expression pattern of extracellular matrix (ECM) components in furcation defects following guided tissue regeneration (GTR) compared with open-flap debridement (OFD). MATERIAL AND METHODS: In 21 dogs, mandibular second and fourth pre-molars were treated with one non-resorbable and three different resorbable membranes. Third pre-molars were treated by OFD. After 2, 4, 8 weeks and 3, 6, and 12 months, tissues were analysed by immunohistochemistry for collagen I (Col-I) and III (Col-III), fibronectin (FN), bone sialoprotein (BSP), and osteopontin (OPN). RESULTS: At 2 weeks, the defect was mainly occupied by FN+ granulation tissue (GT), which was sequentially replaced by new connective tissue expressing FN, Col-I, and increasingly Col-III. Following superficial resorptions by OPN+ osteoclasts and odontoclasts, cementum and bone formation ensued with strong expression of BSP and OPN along bone and tooth surfaces. Deposition of Col-I, FN, BSP and OPN+ cementoid and osteoid became evident after 4 weeks. Extrinsic fibres of cementum and bone stained intensely for Col-III. The newly formed periodontal ligament expressed FN, Col-I, and Col-III, but no BSP or OPN. CONCLUSIONS: The spatial ECM expression was similar for OFD and the different GTR methods, although the timing and quantity of ECM expression were influenced by wound stabilization and inflammatory reactions.     

Emdogain regulation of cellular differentiation in wounded rat periodontium

Emdogain is an enamel matrix derivative that may promote periodontal regeneration by recapitulating critical events in tooth morphogenesis. We hypothesized that Emdogain enhances periodontal regeneration by promoting the differentiation of cells required for the synthesis of periodontal ligament, bone and cementum. Cell differentiation was examined in rat periodontal window wounds in which there is no microbial biofilm or epithelial downgrowth, thereby simplifying the model system. Defects were filled with vehicle control or Emdogain (3 mg/ml or 30 mg/ml). Rats were sacrificed at 7, 14 and 21 d after wounding. Specimens of periodontium were immunostained for osteopontin, bone sialoprotein, osteocalcin as markers of osteogenic differentiation and for alpha-smooth muscle actin, a myofibroblastic marker. Morphometry and 3H-proline radioautography were used for assessment of tissue homeostasis and matrix production. Rats treated with Emdogain (only at 30 mg/ml) showed widening of the periodontal ligament at 7 d; by 14 and 21 d, periodontal ligament width was restored to normal values for all groups. Emdogain exerted no effect on cementum thickness, bone volume, osteoid deposition rates, or extracellular staining for osteopontin, bone sialoprotein or osteocalcin. Further, the percentage of cells with intracellular staining for osteopontin, osteocalcin or bone sialoprotein was unaffected by Emdogain. Staining for alpha-smooth muscle actin was abundant in the repopulating wound but was also unaffected by Emdogain. In conclusion, Emdogain does not apparently affect the expression of differentiation markers or bone matrix protein synthesis in the repopulation response of wounded rat molar periodontium. Therefore the effect of Emdogain on wound healing in the periodontium may be independent of differentiation in the cell populations examined in this model.     

Immunohistochemical study of bone sialoprotein and osteopontin in healthy and diseased root surfaces

BACKGROUND: Periodontal disease is marked by inflammation and damage to tooth-supporting tissues. In particular, damage occurs to factors present in cementum that are thought to have the ability to influence the regeneration of surrounding tissues. Bone sialoprotein and osteopontin are major non-collagenous proteins in mineralized connective tissues associated with precementoblast chemo-attraction, adhesion to the root surface, and cell differentiation. The purpose of this investigation was to determine whether the expression and distribution of bone sialoprotein and osteopontin on root surfaces affected by periodontitis are altered compared to healthy, non-diseased root surfaces. METHODS: Thirty healthy and 30 periodontitis-affected teeth were collected. Following fixation and demineralization, specimens were embedded in paraffin, sectioned, and exposed to antibodies against bone sialoprotein and osteopontin. Stained sections were assessed using light microscopy. RESULTS: Bone sialoprotein was not detected in the exposed cementum (absence of overlying periodontal ligament) of diseased teeth. In most areas where the periodontal ligament was intact, bone sialoprotein was detected for healthy and diseased teeth. For teeth reactive for bone sialoprotein, the matrix of the cementum just below the periodontal ligament was moderately stained. A similar immunoreactivity pattern for osteopontin was observed. CONCLUSIONS: The absence of bone sialoprotein and osteopontin staining along exposed cementum surfaces may be due to structural and compositional changes in matrix components associated with periodontal disease. This may influence the ability for regeneration and new connective tissue attachment onto previously diseased root surfaces.     

Healing of human intrabony defects following regenerative periodontal therapy with a bovine-derived xenograft and guided tissue regeneration

The purpose of the present study was to histologically evaluate the healing of human intrabony defects following treatment with either a bovine-derived xenograft (BDX) and guided tissue regeneration (GTR) [BDX + GTR] or a bovine-derived xenograft mixed with collagen (BDX Coll) and GTR [BDX Coll + GTR]. Eight patients with chronic periodontitis and each with one very deep intrabony defect around a tooth scheduled for extraction were treated with either a combination of BDX + GTR (five patients) or with BDX Coll + GTR (three patients). The postoperative healing was uneventful in all eight cases. After a healing period of 6 months, the teeth or roots were extracted together with some of their surrounding soft and hard tissues and subsequently fixed in 10% buffered formalin. Following decalcification in EDTA, the specimens were embedded in paraffin and 8-µm histological sections were cut in the mesio-distal direction, parallel to the long axes of the teeth. The sections were alternatively stained with hematoxylin and eosin, van Giessons connective tissue stain or with the Ladevigs connective tissue staining method and examined under the light microscope. Generally, formation of new cementum with inserting collagen fibers was found in seven out of the eight treated cases, whereas in the remaining case (treated with BDX + GTR) the healing was characterized by formation of a long junctional epithelium along the debrided root surface and no formation of cementum or bone. In the specimens demonstrating periodontal regeneration the new cementum was always of a cellular type. In most cases, the graft particles were surrounded by bone. In some areas, the bone tissue around the graft particles was connected by perpendicularly inserting collagen fibers to the newly formed cementum on the root surface. The epithelium downgrowth stopped always at the most coronal part of the newly formed cementum. No remnants of the membrane material were observed in any of the biopsies. Connective tissue encapsulation of the graft particles was rarely observed and was limited to the most coronal part of the defects. The findings of the present study provide evidence that treatment of intrabony defects with both BDX + GTR and BDX Coll + GTR may enhance periodontal regeneration in humans.     

Human histologic evaluation of an intrabony defect treated with enamel matrix derivative, xenograft, and GTR

The purpose of the present case report is to clinically and histologically evaluate the healing of one advanced intrabony defect following treatment with an enamel matrix protein derivative (EMD) combined with a bovine-derived xenograft (BDX) and guided tissue regeneration (GTR). One patient with generalized chronic periodontitis and one advanced intrabony defect was treated with EMD + BDX + GTR. Notches were placed in the root at the level of the calculus and alveolar crest to aid histologic identification of new periodontal tissues. Postoperative healing was uneventful. At the 7-month histologic examination, healing in the intrabony component of the defect was characterized by formation of new connective tissue attachment (new cellular cementum with inserting collagen fibers) and new bone in the intrabony component. The BDX particles were surrounded by bone-like tissue. No direct contact between the graft particles and root surface (cementum or dentin) was observed. Healing in the suprabony defect component occurred through epithelial downgrowth that stopped at the level of the coronal notch. The BDX particles were entirely encapsulated in dense connective tissue, without any signs of bone formation. The present case report shows formation of new attachment apparatus consisting of new bone, cementum, and periodontal ligament in the intrabony component of one human defect treated with EMD + BDX + GTR.     

Immunohistochemical evaluation of matrix molecules associated with wound healing following regenerative periodontal treatment in monkeys

The aim of the study was to investigate immunohistochemically the expression of matrix molecules associated with periodontal tissues reformed after regenerative periodontal treatment. Chronic intrabony defects were treated with guided tissue regeneration, enamel matrix proteins, the combination of both, or access flap surgery. Five months after healing, the animals were killed, and the healed periodontal tissues were evaluated immunohistochemically by means of polyclonal antibodies against osteopontin, collagen I, and collagen III. The intact (nontreated) parts of the periodontium served as controls. As a general observation, the staining for all investigated matrix molecules appeared to be stronger within the regenerated tissues than in the intact ones. The results failed to reveal any differences in terms of staining intensity or distribution pattern of investigated matrix molecules between the four different treatments. Osteopontin expression was most intense at the border near the newly formed cementum and bone. In the regenerated periodontium, collagens I and III were localized throughout the entire periodontal ligament connective tissue. In the regenerated periodontal ligament, collagen III displayed more intense staining than collagen I. The present results suggest that: (1) even after a 5-month period following surgical periodontal therapy, extracellular matrix molecules associated with wound healing and/or remodelling are more strongly expressed in regenerated than in intact tissues and (2) once an environment for periodontal regeneration has been created, the expression of extracellular matrix molecules associated with the healing process seems to display the same pattern, irrespective of treatment modality.     

Effects of bone morphogenetic protein-6 on periodontal wound healing in a fenestration defect of rats

BACKGROUND: Bone morphogenetic proteins (BMPs) may play significant roles in bone formation. The ability of BMP-6 to promote wound healing has been chosen as the subject of this investigation. In this study, a synthetic rat BMP-6 polypeptide was applied to a periodontal fenestration defect in rats to elucidate the effects of BMP-6 on periodontal wound healing. MATERIAL AND METHODS: Following surgery to create a bony window on the buccal aspects of mandibular molar roots, 24 male Sprague Dawley rats were divided into four groups according to BMP application (0, 1, 3 and 10 microg, respectively). Animals were killed after 28 days and the mandible taken for histological examination. Histometric measurements were performed on sections selected from three levels (coronal, middle and apical levels; with 240 microm apart from the central) of the defect. New bone and cementum formation (including area and thickness) were analyzed and compared. RESULTS: In general, minimal new bone was observed on the surgically created defects in the non-BMP group, whereas a complete osseous healing occurred in all BMP-6 treated animals. New bone formation (both in area and thickness) was significantly influenced by both the dosage and the examining level, whereas new cementum formation was affected by dosage only. An increase in bone and cementum formation was noted in all three BMP groups when compared with the control group at all examined levels. Among the BMP groups, greatest new bone and cementum formation were noted in the 3 microg group. New cementum thickness increased on the cementum surfaces of the defects compared with the dentinal surfaces in all study groups. CONCLUSION: An increase in new bone and cementum formation was noted after applying a synthetic BMP-6 polypeptide to a periodontal fenestration defect in rats. Therefore, we suggest that BMP-6 may play a certain role in periodontal regeneration.     

Expression of bone matrix protein mRNAs by primary and cloned cultures of the regenerative phenotype of human periodontal fibroblasts

The successful regeneration of periodontal tissues is dependent, in part, on the ability of cells to reconstitute the mineralized tissues of cementum and bone. The aim of the present study was to characterize regeneration-associated cells in terms of their ability to express mineralized tissue macromolecules. Following guided tissue regeneration, cell cultures were established from regenerating tissue, periodontal ligament, and gingiva. Additionally, these cells were transfected, and single-cell-derived clones were established. Following treatment with platelet-derived growth factor-BB and insulin-derived growth factor-1, the presence of mRNA for alkaline phosphatase, osteocalcin, bone sialoprotein, osteopontin, and bone morphogenetic proteins-2 and -4 was assessed. The three cell types expressed similar mRNA levels for alkaline phosphatase, bone morphogenetic protein-2, and bone morphogenetic protein-4, whereas the expression of osteopontin, osteocalcin, and bone sialoprotein was greater in the periodontal ligament and regenerating tissue fibroblasts compared with the gingival fibroblasts. The two growth factors did not affect the expression of any of the genes. This study has identified markers that correlate with the known ability of periodontal ligament and regenerating tissue-derived fibroblasts to facilitate regeneration of the mineralized tissues of the periodontium.     

Collagen implants do not preserve periodontal ligament homeostasis in periodontal wounds

An improved understanding of the differentiation of periodontal ligament cells could facilitate the development of new treatment approaches for overcoming the loss of specialized cell types caused by periodontitis. To study healing of wounded periodontal tissues and the differentiation of mineralizing connective tissue cells in periodontal ligament, we have examined the influence of wound size and collagen implantation on the regeneration of periodontium and on immunohistochemical staining for osteopontin and bone sialoprotein. Four groups of Wistar rats were wounded by drilling through the alveolar bone and by extirpation of the periodontal ligament. Wounds were 0.6 or 1.8 mm in diameter and defects were either implanted with collagen gels or were treated without implants. Rats were killed at 1 wk or 2 months after wounding and tissue sections were stained with monoclonal antibodies against rat osteopontin and bone sialoprotein. Collagen implants strongly increased staining for osteopontin and bone sialoprotein in defects at 1 wk. By 2 months alveolar bone healed completely regardless of the wound size but in large defects, periodontal ligament width was significantly reduced with or without implants. In large wounds at 2 months, collagen implants inhibited bone regeneration and there was stronger staining for osteopontin and bone sialoprotein in the bone replacing the implant, indicating that collagen prolonged bone remodelling. We conclude that implantation of exogenous collagen affects alveolar bone healing but does not preserve the width of the regenerated periodontal ligament. Therefore collagen does not appear to contribute to homeostasis in the periodontium following wounding.     

Wound healing following regenerative procedures in furcation degree III defects: histomorphometric outcomes

Degree III furcation involvements were surgically created at four first molars in each of three monkeys. Following 6 weeks of healing, full-thickness flaps were elevated. Following 24% EDTA gel conditioning, the defects were treated with one of the following: (1) enamel matrix proteins (EMD), (2) guided tissue regeneration (GTR) or (3) a combination EMD and GTR. The control defects did not receive any treatment. After 5 months of healing, the animals were sacrificed. Three 8 μm thick histological central sections, 100 μm apart, were used for histomorphometric analysis in six zones of each tooth either within the furcation area or on the pristine external surface of the root. In all specimens, new cementum with inserting collagen fibres was formed. Following GTR or GTR + EMD, cementum was formed up to and including the furcation fornix indicating complete regeneration on the defect periphery. Periodontal ligament fibres were less in all four modalities compared to pristine tissues. In the teeth treated with GTR and GTR + EMD a higher volume of bone and periodontal ligament tissues was observed compared to EMD. After 5 months of healing, regenerated tissues presented quantitative differences from the pristine tissues. In the two modalities where GTR alone or combined with EMD was used, the regenerated tissues differed in quantity from the EMD-treated sites.     

Periodontal repair in dogs: a bioabsorbable calcium carbonate coral implant enhances space provision for alveolar bone regeneration in conjunction with guided tissue regeneration

BACKGROUND: Collapse or compression of a barrier device into a periodontal defect or onto the root surface compromises outcomes following guided tissue regeneration (GTR). Bone biomaterials have been suggested to support regeneration of alveolar bone and to improve space provision with GTR devices. The objective of this study was to evaluate space provision, alveolar bone, and cementum regeneration following use of a bioabsorbable, calcium carbonate biomaterial in conjunction with GTR. METHODS: Routine, critical size, 5 to 6 mm, supraalveolar, periodontal defects were created in 5 young adult beagle dogs. Alternate jaw quadrants in consecutive animals received GTR and the coral biomaterial (cGTR) or GTR alone. The animals were euthanized 4 weeks postsurgery and tissue blocks processed for histometric analysis. RESULTS: The coral implant particles were surrounded by newly-formed bone or immersed in connective tissue and appeared to resorb and be replaced by bone. There was limited, if any, appreciable cementum regeneration. Space provision was enhanced in cGTR compared to GTR sites (6.1 +/- 1.6 versus 2.4 +/- 0.8 mm2; P<0.05). Bone regeneration (height) was significantly increased in cGTR compared to GTR sites averaging 1.9 +/- 0.6 and 1.2 +/- 0.6 mm, respectively (P<0.05). Bone regeneration (area) was 2-fold greater in cGTR sites compared to the GTR control (3.3 +/- 1.8 versus 1.4 +/- 0.5 mm2), however the difference was not statistically significant (P>0.05). CONCLUSIONS: The coral implant significantly enhanced space provision for GTR while alveolar bone formation appeared to be enhanced by its use. Increased healing intervals are needed to fully understand the biologic value of the coral implant as an adjunct to GTR.     

低强度脉冲超声波联合引导组织再生术促进牙周骨开窗缺损修复的动物实验

目的 探讨低强度脉冲超声波(low intensity pulsed ultrasound,LIPUS)联合引导组织再生术(guided tissue regeneration,GTR)对Beagle犬尖牙牙周骨开窗缺损的修复效应.方法 构建4只Beagle犬尖牙颊侧区根中1/3处牙周骨开窗缺损模型.将4只Beagle犬的16颗双侧上、下颌尖牙(实验牙)按简单随机法平均分配为4组:①实验1组,LIPUS(60 mW/cm2,20 min/d)处理+GTR+牙周骨质缺损组;②实验2组,LIPUS(60 mW/cm2,20 min/d)处理+牙周骨质缺损组;③实验3组,GTR+牙周骨质缺损组;④空白对照组,牙周骨质缺损组.实验共进行28 d.每14天分别测量各组处理前后实验牙牙龈表面温度,并行Wilcoxon符号秩和检验.4周后观察脱钙骨组织切片,分析各组尖牙牙周骨开窗缺损的组织学修复效果.结果 临床观察各组实验牙牙周均愈合良好.各组处理前后的牙龈表面温度差值[M(Q)]分别为:实验1组:0.225(0.463)℃;实验2组:0.265(0.133)℃;实验3组:0.09(0.115)℃;空白对照组:-0.175(0.370)℃,实验1、2组每次处理前后温度变化差异均有统计学意义(P值均为0.027).脱钙骨组织切片观察显示实验1组骨缺损内充满团状新生骨组织,成骨细胞增生活跃,骨胶原较成熟,Masson染色红染明显;实验3组新生牙骨质、牙槽骨较实验2组和空白对照组多,新生骨胶原成熟度不高,Masson染色呈红蓝相间;实验2组新生骨胶原成熟度较实验3组和空白对照组高,Masson染色红染明显;空白对照组可见少量新生牙骨质沿切迹处生长,新生骨胶原不成熟,Masson染色呈红蓝相间.结论 LIPUS具有促进牙周骨开窗缺损修复的潜能,LIPUS与GTR结合可能更利于牙周组织缺损的修复.

Abstract：

Objective To evaluate the effects of low intensity pulsed ultrasound(LIPUS)combined with guided tissue regeneration(GTR) for the repair of the periodontal fenestration defect at the canines in Beagle dogs. Methods Four Beagle dogs were used for establishing the periodontal fenestration defect. Sixteen canines of four Beagle dogs were simple randomly assigned into experimental group 1[LIPUS(60 mW/cm2,20 min/d)irradiation + GTR + the periodontal fenestration defect], experimental group 2[LIPUS(60 mW/cm2,20 min/d)irradiation + the periodontal fenestration defect], experimental group 3(GTR+ the periodontal fenestration defect) and control group(the periodontal fenestration defect). Experiments conducted 28 d. The temperature of the gingive′s surface of each group was tested every 14 days(analyzed by Wilcoxon rank sum test with SPSS 13.0). The demineralized bone tissue slices of the periodontal fenestration were obtained for histologic staining after 4 weeks treatment. Results Clinically all the treatment groups healed well. The change of gingive′s surface temperature[M(Q)] before and after LIPUS irradiating were:0.225(0.463)℃(experimental group 1),0.265(0.133)℃ (experimental group 2),0.090(0.115)℃(experimental group 3);-0.175(0.370)℃(control group). The P value of experimental group 1 and 2 with pre-and post-treatment each time were both 0.027. Histology of the demineralized bone tissue revealed that in experimental group 1, the bone defect was filled with fresh bone-like tissues, proliferatively active osteoblasts and newly formed cementum-like tissues along the defect surface. In experimental group 3, there were more new cementum-and bone-like tissues than in experimental group 2 and control group. In experimental group 2,the new bone collagen was more mature than in experimental group 3 and control group. In control group,there was less growth of new cementum along the notch, and the new bone collagen was immature. Conclusions LIPUS combined with GTR may have the potential of promoting the repair of periodontal fenestration defect.     

Histologic evaluation of an allogeneic mineralized bone matrix in the treatment of periodontal osseous defects

The aim of this study was to evaluate the potential of an allogeneic bone matrix to regenerate new bone, cementum, and periodontal ligament around a previously diseased root surface. Four patients with severe chronic periodontitis and teeth with hopeless periodontal or restorative prognoses participated in this study. One tooth with a severe intraosseous defect was selected per patient. At baseline, measurements of probing depth, gingival recession, and clinical attachment level were obtained. Following flap reflection, a root notch was placed at the apical extent of the calculus; the root was debrided, and the allogeneic bone graft material was placed into the defect. After a minimum of 6 months of healing, the teeth were removed en bloc and prepared for histologic examination. Two of four teeth demonstrated regeneration of new bone, cementum, and periodontal ligament. One tooth healed by new connective tissue attachment, and another by junctional epthelium.     

Biomimetic surface modification using synthetic oligopeptides for enhanced guided bone regeneration in beagles

Background: In previous studies, oligopeptide corresponding to the cell‐binding domains of bone morphogenetic proteins that bind to bone morphogenetic protein receptor enhanced the bone regenerative capacity of bovine bone minerals (BBM). The aim of this study is to evaluate the ability of BBM coated with oligopeptide to promote periodontal regeneration in a 1‐wall intrabony defect model in dogs. Methods: The second and third mandibular premolars and first molars of six adult beagles were extracted bilaterally, and the extraction sites were allowed to heal for 10 weeks. The 1‐wall intrabony defects were prepared bilaterally on the mesial and distal side of the fourth mandibular premolars. Twenty‐four intrabony defects were assigned to four treatment groups: 1) open flap debridement; 2) guided tissue regeneration (GTR); 3) GTR with a collagen membrane and BBM; and 4) GTR with a collagen membrane and BBM coated with the oligopeptide (Pep‐BBM). The animals were sacrificed 10 weeks after surgery. For the histometric analysis, defect height, junctional epithelium migration, new cementum, new bone height, and new bone area were measured. New bone volume was measured using microcomputed tomography. Results: Wound healing was generally uneventful. For junctional epithelium migration, the BBM and Pep‐BBM groups exhibited mean (± SE) values of 0.53 ± 0.41 and 0.48 ± 0.30 mm, and for new cementum height, 1.71 ± 0.46 and 2.50 ± 2.00 mm, respectively. For junctional epithelium migration and cementum regeneration, there were no significant differences between the two groups. The mean (± SE) values of new bone height and new bone volume in the Pep‐BBM group (3.88 ± 0.31 mm and 32.35% ± 9.60%) were significantly greater than the mean values for the BBM group (2.60 ± 0.41 mm and 20.56% ± 1.89%). For bone regeneration, the Pep‐BBM group showed superior results compared to the BBM group with statistically significant differences. Conclusions: Through various parameters to evaluate periodontal regeneration, this oligopeptide coating influenced only the ability of BBM to promote bone regeneration in 1‐wall intrabony defects in beagles. Junctional epithelium migration and cementum regeneration were not affected by this oligopeptide coating, and further investigations with special focus on regeneration of the periodontal ligament are necessary.     

Periodontal regeneration of a class II furcation defect utilizing a bioabsorbable barrier in a human. A case study with histology

This case report describes human histologic data of periodontal regeneration following guided tissue regeneration therapy (GTR) with a bioabsorbable barrier composed of polylactic acid. The tooth that was examined was part of a previously published study of the clinical effects of GTR therapy without the use of bone or bone substitutes on Class II furcation defects. Twenty-five months following the surgical procedure, the tooth was extracted for non-periodontal reasons. During this extraction, the bone within the furcation that was treated in the study was luxated with the tooth. At the completion of the study (month 12), the furcation's vertical probing depth had decreased by 2 mm with a 2 mm gain in clinical attachment. The horizontal furcation measurement decreased by 3 mm. Following extraction, the tooth was prepared for light microscopy and sectioned in the mesial-distal plane. Reference notches were not placed in the tooth at the time of surgery as there were no plans to perform histologic analysis in the study. However, using the buccal root prominences and what we interpreted to be root planing marks on the cementum, we were able to demonstrate that complete periodontal regeneration occurred on the root surface that was exposed to the pocket environment prior to surgery. New alveolar bone, cementum, and periodontal ligament were consistently observed throughout the furcation in the areas that demonstrated clinical attachment gain and a decrease in horizontal probing depth. This case report adds to the accumulating evidence of histologic periodontal regeneration following guided tissue regeneration with bioabsorbable polylactic acid barriers.     

Emdogain in regenerative periodontal therapy. A review of the literature

The goal of regenerative periodontal therapy is the reconstitution of the lost periodontal structures (i.e. the new formation of root cementum, periodontal ligament and alveolar bone). Results from basic research have pointed to the important role of the enamel matrix protein derivative (EMD) in the periodontal wound healing. Histological results from animal and human studies have shown that treatment with EMD promotes periodontal regeneration. Moreover, clinical studies have indicated that treatment with EMD positively influences periodontal wound healing in humans. The goal of the current overview is to present, based on the existing evidence, the clinical indications for regenerative therapy with EMD. Surgical periodontal treatment of deep intrabony defects with EMD promotes periodontal regeneration. The application of EMD in the context of non-surgical periodontal therapy has failed to result in periodontal regeneration. Surgical periodontal therapy of deep intrabony defects with EMD may lead to significantly higher improvements of the clinical parameters than open flap debridement alone. The results obtained following treatment with EMD are comparable to those following treatment with GTR and can be maintained over a longer period. Treatment of intrabony defects with a combination of EMD + GTR does not seem to additionally improve the results compared to treatment with EMD alone or GTR alone. The combination of EMD and some types of bone grafts/bone substitutes may result in certain improvements in the soft and hard tissue parameters compared to treatment with EMD alone. Treatment of recession-type defects with coronally repositioned flaps and EMD may promote formation of cementum, periodontal ligament and bone, and may significantly increase the width of the keratinized tissue. Application of EMD seems to provide better long-term results than coronally repositioned flaps alone. Application of EMD may enhance periodontal regeneration in mandibular Class II furcations. The clinical results are comparable to those obtained following GTR.     

Clinical and histologic evaluation of a granular bovine bone biomaterial used as an adjunct to GTR with a bioresorbable bovine pericardium collagen membrane in the treatment of intrabony defects

Background: The aim of the present study is to evaluate the clinical and histologic healing of deep intrabony defects treated with guided tissue regeneration (GTR) with a collagen membrane from bovine pericardium and implantation of granular bovine bone biomaterial. Methods: Thirty patients with one deep, combined 1‐ and 2‐wall intrabony defect exhibiting a probing depth ≥6 mm and an associated intrabony defect ≥3 mm were treated with GTR with a bioresorbable collagen membrane from bovine pericardium and adjunct implantation of a granular bovine bone biomaterial. The clinical results were evaluated 1 and 3 years after surgery. In addition, five teeth fulfilling the inclusion criteria but scheduled for extraction because of advanced periodontitis or restorative considerations were treated similarly and then extracted along with a portion of their surrounding periodontal tissues for histologic evaluation 6 months after surgery. Results: Healing was uneventful in all patients. Significant clinical improvements were observed at 1 and 3 years postoperatively (P <0.01; probing depth averaged 4.4 ± 1.6 and 4.7 ± 1.4 mm and clinical attachment level gain was 3.9 ± 1.4 and 3.5 ± 1.3 mm, respectively). The histologic evaluation revealed formation of new cellular cementum and new periodontal ligament in four of the five cases. In general, the xenograft particles seemed to be mostly embedded in connective tissue without any evidence of new bone formation. Conclusion: GTR treatment of intrabony defects with the collagen membrane from bovine pericardium and adjunct implantation of the new bovine bone biomaterial may result in significant clinical improvements that can be maintained over a period of 3 years, and regeneration of cementum and periodontal ligament, but without bone formation.     

Root cementum may modulate gene expression during periodontal regeneration: a preliminary study in humans

BACKGROUND: Previous data demonstrated that root cementum may affect periodontal regeneration. As such, this study aimed to explore further possible mechanisms involved in this process by investigating in humans whether root cementum modulates gene expression in the regenerating tissue formed under membrane-protected intrabony defects. METHODS: Thirty subjects with deep intrabony defects (> or =5 mm; 2- or 3-wall) were selected and assigned to the control or test group. The control group received scaling and root planing with the removal of granulation tissue and root cementum; the test group underwent removal of granulation tissue and soft microbial deposits by cleaning the root surface with a microbrush and saline solution, aiming at cementum preservation. Guided tissue regeneration (GTR) was applied to both groups. Twenty-one days later, the newly formed tissue under the membrane was assessed for the expression of the following genes: alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN), platelet-derived growth factor-alpha (PDGFA), bone sialoprotein (BSP), and basic fibroblast growth factor (bFGF). RESULTS: Data analysis demonstrated that mRNA levels for PDGFA, BSP, and bFGF were higher in the sites where root cementum was kept in place compared to the sites where root cementum was removed completely as part of the periodontal therapy (P <0.05); in contrast, OCN levels were lower (P <0.05). No difference for ALP or OPN was observed between the control and test groups (P >0.05). CONCLUSION: Root cementum may modulate the expression of growth and mineral-associated factors during periodontal regeneration.