The root surf ace and regeneration; present therapeutic limitations and future biologic potentials

Abstract An ultimate goal of periodontal therapy is predictable regeneration of a periodontium at the site of a previous marginal periodontitis. Current clinical therapeutic techniques result in repair, and not regeneration with formation of a new connective tissue attachment. Studies have indicated that surface demineralization of dentin from root surfaces predisposes toward a new connective tissue attachment, and this attachment may take place in an environment lacking periodontal progenitor cell populations. The rôle of the root surface is considered regarding inhibition and facilitation of these various connective tissue responses.     

Mechanisms of new attachment formation

Abstract A goal of periodontal therapy is predictable regeneration of a periodontium at the site of a previous marginal periodontitis. Current clinical therapeutic techniques result in repair, and not regeneration with formation of a new connective-tissue attachment. Investigations have shown that surface demineralization of dentin predisposes toward a new connective-tissue attachment, and this attachment may take place in an environment lacking periodontal progenitor cell populations. The role of the root surface is considered regarding inhibition and facilitation of these connective tissue responses.     

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.     

Fibre guiding scaffolds for periodontal tissue engineering

The periodontium is a highly hierarchically organized organ composed of gingiva, alveolar bone, periodontal ligament and cementum. Periodontitis leads to the destruction of hard and soft tissues ultimately leading to a loss of the teeth supporting apparatus. Current treatments are capable of limiting the disease progression; however, true regeneration, characterized by perpendicularly oriented periodontal ligament fibre attachment to cementum on the root surface remains challenging. Tissue engineering approaches have been developed to enhance regeneration via micro-engineered topographical features, purposely designed to guide the insertion of the regenerated ligament to the root surface. This review reports on the recent advancements in scaffold manufacturing methodologies for generating fibre guiding properties and provides a critical insight in the current limitations of these techniques for the formation of functional periodontal attachment.     

New attachment and tissue regeneration.

In periodontology, the possibility of stimulating new connective tissue attachment to previously diseased root surfaces, and the regeneration of the supporting periodontal tissues destroyed by periodontitis have been under study for some years. This paper reviews the different experimental methods used to prepare root surfaces for optimal regeneration and attachment of periodontal tissues. The mechanisms of blood clot formation, adhesion to the root surface and wound maturation are considered, as are the future needs for research in this subject.     

经典Wnt信号通路与牙周膜干细胞成骨分化

牙周炎是口腔最常见的疾病之一,累及牙周支持组织,随着疾病的进展将引起附着丧失、牙周袋形成、牙槽骨吸收,最终导致牙齿松动脱落。因被牙周炎破坏吸收的牙槽骨自愈能力十分有限,所以牙周炎的治疗目标是在彻底清除菌斑生物膜的基础上,争取获得较多的牙周组织再生。牙周膜干细胞作为最适宜进行牙周组织再生的细胞,被广泛研究。Wnt信号通路分为经典Wnt通路和非经典Wnt信号通路,为十分复杂而高度保守的通路传导途径。该通路与牙周膜干细胞成骨分化的关系十分密切,牙周膜干细胞的成骨分化又对牙周组织再生有重要意义。该文对经典Wnt信号通路与牙周膜干细胞成骨分化的研究概况作一综述。     

The regenerative potential of the periodontal ligament

The current decline in the incidence of dental caries indicates that patients will retain most of their dentition. Reconstruction or regeneration of the entire attachment apparatus, including the periodontal ligament, cementum, and bone, is an attainable therapeutic goal. Clinical treatments designed to reattach connective tissue to exposed root surfaces commonly result in the formation of a long junctional epithelial attachment. This attachment is probably not an effective barrier to bacterial toxins and may allow recurrent pocket formation. To enhance reattachment of connective tissue, root-conditioning agents have been used but their clinical efficacy is questionable. Restoration of destroyed alveolar supporting bone by means of allogenic and autogenous bone-grafting materials has been recommended, but these procedures do not restore the cementum and PDL. Attempts to promote regeneration of the entire attachment apparatus have included clinical studies that used mechanical means to promote repopulation of affected root surfaces by periodontal ligament fibroblasts and prevent contact of epithelial or gingival connective tissue cells. Results thus far have been encouraging, but the practicality of these techniques may be limited. However, these studies have demonstrated that if only PDL cells contact the root surface during healing, a normal PDL can re-form. Dental follicle tissue is capable of inducing the formation of cementum-like structures and is clearly the cell population responsible for cementum and PDL formation. Recent research has demonstrated that the dental papilla probably shares the same inductive capabilities as the dental follicle.(ABSTRACT TRUNCATED AT 250 WORDS)     

The treatment of a localized osseous sequestrum with porous bone mineral in combination with a collagen membrane and resorbable bone pins

The ultimate goal of periodontal therapy should not be limited to the establishment and maintenance of periodontal health. The potential regeneration of the hard and soft periodontal tissues lost due to disease also should be considered. This case presentation evaluated a new surgical technique for the treatment of a variety of localized bone defects, utilizing porous bone mineral in combination with collagen membrane and resorbable bone pins.     

Mesenchymal stem cells from the oral cavity and their potential value in tissue engineering

Periodontal disease is one of the most common conditions affecting humans, and current treatment strategies, which focus on the removal and long‐term control of dental plaque, are generally successful in eliminating active disease and promoting tissue repair. However, regeneration of the supporting structures of the tooth remains an elusive goal and a challenge. The formation of new bone and cementum with supportive periodontal ligament is the ultimate objective, but current regeneration therapies are incapable of achieving this in a predictable way. The regeneration of periodontal tissue requires a combination of fundamental events, such as appropriate level and sequencing of regulatory signals, the presence of progenitor cells, an extracellular matrix or carrier and an adequate blood supply. Based on tissue‐engineering concepts, the regeneration process may be modulated by manipulating the signaling pathways of regulatory molecules, the extracellular matrix or scaffold, or the cellular components. The identification of mesenchymal stem cells from bone marrow started a new era in regenerative medicine. Tissue engineering using mesenchymal stem cells became a therapeutic option with several advantages, including high‐quality regeneration of damaged tissues without the formation of fibrous tissue, minimal donor‐site morbidity compared with autografts and a low risk of autoimmune rejection and disease transmission. The aim of this review was to describe the main sources of mesenchymal stem cells from tissues in the oral cavity and the potential of these cells in regenerative therapy. Special attention is paid to gingival tissue‐derived mesenchymal stem cells because they represent the most accessible source of stem cells in the human mouth.     

Periodontal regeneration techniques for treatment of periodontal diseases

The ultimate goal of periodontal therapy is the regeneration of structures lost to disease. Conventional surgical approaches such as open-flap debridement offer only limited regeneration potential.Currently, surgical procedures for predictable regeneration of periodontal tissues are being developed, analyzed, and employed in clinical practice. This article addresses current trends in periodontal regeneration. Various materials/agents such as bone replacement grafts, barrier membranes, and biologic modifiers currently used for the regeneration of periodontal infrabony and furcation defects are discussed.     

牙骨质相关细胞的研究进展

到目前为止，人们对牙骨质的了解仍较少。人牙骨质再生被认为是牙周病暴露的根面上牙周组织再生的关键。本文回顾了学者们对牙骨质及其相关细胞的研究，阐述了形成牙骨质前体细胞的位置以及成牙骨质细胞的起源。     

Growth factors in periodontal regeneration

Abstract:  Inflammatory periodontal disease is an almost ubiquitous disorder in the adult population. Cases or sites with moderate to advanced disease often continue to show signs of inflammation after non-surgical approach. Our current understanding of periodontal healing is based on a hypothesis by Melcher who proposed that the cell type that repopulates the exposed root surface at the periodontal repair site will define the nature of the attachment/repair that take place. If mesenchymal cells from periodontal ligament/perivascular region of the bone proliferate and colonize the root surface, regeneration occurs. Growth factors are natural cell products that are released or activated when cell division is needed. This action typically occurs during such events as wound healing or tissue regeneration. Activated platelets at the wound margins release several growth factors such as platelet-derived growth factor (PDGF), transforming growth factor (TGF)-α, epidermal growth factor etc. Cells adjacent to the injured site also are induced to release growth factors such as insulin-like growth factor-I, PDGF, TGF-α and TGF-α within a few hours after injury. In periodontal regeneration, the coronal re-establishment of the periodontal ligament (PDL) is required together with corresponding cementum and supporting alveolar bone. Thus, agents which promote periodontal ligament fibroblast (PLF) proliferation and migration as well as collagen biosynthesis would appear to be mediators for enhancing new PDL formation. When combinations or cocktails of different factors are used, greater repair is achieved than when individual factors are applied.     

Regenerative periodontal therapy

Regenerative periodontal therapy comprises procedures which are specially designed to restore parts of the tooth supporting apparatus which have been lost due to periodontitis. A procedure must fulfill certain criteria to be considered a therapy which encourages regeneration. This paper discusses a variety of surgical approaches including root surface conditioning, the placement of bone garfts or bone substitute implants and the use of organic or synthetic barrier membranes (GTR). Evidence is presented that regenerative surgery utilising the GTR principle fulfills all the criteria required of a surgical procedure to be considered a procedure leading to periodontal regeneration.     

Periodontal regeneration

Untreated periodontal disease leads to tooth loss through destruction of the attachment apparatus and tooth-supporting structures. The goals of periodontal therapy include not only the arrest of periodontal disease progression,but also the regeneration of structures lost to disease where appropriate. Conventional surgical approaches (e.g., flap debridement) continue to offer time-tested and reliable methods to access root surfaces,reduce periodontal pockets, and attain improved periodontal form/architecture. However, these techniques offer only limited potential towards recovering tissues destroyed during earlier disease phases. Recently, surgical procedures aimed at greater and more predictable regeneration of periodontal tissues and functional attachment close to their original level have been developed, analyzed, and employed in clinical practice. This paper provides a review of the current understanding of the mechanisms, cells, and factors required for regeneration of the periodontium and of procedures used to restore periodontal tissues around natural teeth. Targeted audiences for this paper are periodontists and/or researchers with an interest in improving the predictability of regenerative procedures. This paper replaces the version published in 1993.     

Current concepts in periodontal bioengineering

Repair of tooth supporting alveolar bone defects caused by periodontal and peri-implant tissue destruction is a major goal of reconstructive therapy. Oral and craniofacial tissue engineering has been achieved with limited success by the utilization of a variety of approaches such as cell-occlusive barrier membranes, bone substitutes and autogenous block grafting techniques. Signaling molecules such as growth factors have been used to restore lost tooth support because of damage by periodontal disease or trauma. This paper will review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Several different polymer delivery systems that aid in the targeting of proteins, genes and cells to periodontal and peri-implant defects will be highlighted. Results from preclinical and clinical trials will be reviewed using the topical application of bone morphogenetic proteins (BMP-2 and BMP-7) and platelet-derived growth factor-BB (PDGF) for periodontal and peri-implant regeneration. The paper concludes with recent research on the use of ex vivo and in vivo gene delivery strategies via gene therapy vectors encoding growth promoting and inhibiting molecules (PDGF, BMP, noggin and others) to regenerate periodontal structures including bone, periodontal ligament and cementum.     

Effect of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS) on healing in 3-wall intrabony defects in dogs

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier is being evaluated as a candidate therapy for periodontal regeneration. The objective of this study was to evaluate regeneration of alveolar bone and cementum, and associated root resorption and ankylosis following surgical implantation of rhBMP-2/ACS in a canine clinical model. METHODS: Bilateral 3-wall intrabony periodontal defects were surgically induced in the premolar region in the maxilla and mandible in 8 young adult Korean mongrel dogs. The defects in each animal received rhBMP-2/ACS (rhBMP-2 at 0.2 mg/ml, total implant volume/defect approximately 0.1 ml) or buffer/ACS, or served as sham-operated controls. Surgeries were sequenced for each animal to provide postmortem observations following 8- and 24-week healing intervals. Treatment outcomes were evaluated using clinical, radiographic, and histometric parameters. RESULTS: Surgical implantation of rhBMP-2/ACS resulted in accelerated enhanced bone formation in the 3-wall intrabony periodontal defects but in no apparent enhancement of cementum regeneration. rhBMP-2/ACS did not appear to be associated with aberrant healing events such as root resorption and ankylosis under these simulated clinical conditions. CONCLUSIONS: Surgical implantation of rhBMP-2/ACS may be used safely to support regeneration of alveolar bone in intrabony periodontal defects in dogs without aberrant events such as root resorption or ankylosis complicating the regenerative procedure. rhBMP-2/ACS does not appear to have a significant effect on cementum regeneration and formation of a functional periodontal ligament in this model.     

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牙周手术治疗主要是为了消除牙周袋,建立生理性的软、硬组织形态,促进牙周组织修复和再生,建立新的牙周附着关系,恢复美观和功能需要.现代牙周手术往往包含软、硬组织的再生手术,而手术的成功,必须依赖实施规范的牙周外科操作,才能提高手术成功率.随着各种新技术和新材料用于牙周手术治疗,牙周手术的结果才会实现组织再生.     

A review of osseous resective surgery.

The treatment of periodontal diseases associated with attachment loss has involved a variety of approaches. While the goal of periodontal surgical treatments is to access the root surfaces for proper debridement, the decision to remove or reshape the supporting bone has been controversial. This paper will address the controversy as well as discuss surgical pocket therapy directed toward pocket reduction through recontouring the underlying bone.     

Principles and techniques of guided tissue regeneration

Guided tissue regeneration is an accepted technique to promote new attachment in periodontal therapy. It is supported by sound basic research indicating that the definitive factor in the obtainment of regeneration is the source from which the cells repopulating the exposed root surface originate. These studies have indicated that cells proliferating from the periodontal ligament have the greatest potential for achieving new attachment. The use of barriers during periodontal surgery permits the possibility of periodontal ligament proliferation toward the exposed root at the same time that epithelial and gingival connective tissue proliferation is blocked. Studies in which Gore-Tex periodontal material has been used as a barrier have shown positive results in animal and clinical studies. Histologically, the formation of new cementum, bone, and periodontal ligament has been demonstrated. Clinically, beneficial results have been documented in the treatment of intrabony defects with three-wall, two- to three-wall, or funnel-shaped topography. Also, Class II furcations with or without a vertical component have been treated successfully by guided tissue regeneration.     

牙周膜干细胞的研究进展

牙周病是一种由菌斑微生物引起的慢性感染性疾病,可引起牙周支持组织的破坏和丧失,最终导致牙齿松动脱落。牙周病治疗的最终目标是修复和重建受损的牙周支持组织。从牙周膜中分离获取的间充质干细胞具有成体干细胞的特性及多重分化潜能,可以分化为骨组织和牙周支持组织等多种类型的组织,这对牙周组织修复再生和牙周组织工程具有重大意义,因而备受关注。本文就牙周膜干细胞、牙周膜干细胞的生物学特性、牙周膜干细胞的影响因素及其调控机制等研究进展作一综述。