梁艳硕士翻译 Griffin校对

With the possible exception of implant fixtures (and their prosthetic attachments), no area in periodontics has proliferated so rapidly as periodontal regeneration materials. Today commercial preparations are marketed almost as soon as the first piece of research is published. Some pan out and some are gone as fast as last week's average movie.

 

在牙周病学里，也许除了种植体固定装置(和它们的修复附件)，没有比牙周再生材料发展得更加迅速的领域了。如今，几乎伴随着研究内容第一部分的公布，产品制剂就开始上市销售了。其中一些获得了成功，另一些则像上周上映的普通电影一样迅速消失。

 

Now, with the advent of ridge augmentation to receive implants and sinus lifts, grafting materials are being designed for specific applications. Some are engineered to maximize the space for bone ingrowth while others provide a scaffold and readily available inorganic components of bone that migrating reparative cells can utilize. Biologic modifiers are being introduced to increase the likelihood of regeneration.

 

现今，为了使种植体相容和上颌窦提升，出现了牙槽嵴增高术，移植材料的设计也随之趋于特殊用途。一些设计用于增加骨内部生长空间，使其最大化；其他设计则为移植修复细胞提供可利用的支架以及生物相容性良好的骨无机成分。生物改性剂现在也正引入治疗中，提高组织再生。

 

In addition, some manufacturers have begun to individually test donor materials, such as allografts from tissue banks, to determine the graft's ability to induce bone formation in lab animals in areas which would not normally form bone. This increases the likelihood that the graft will actually induce surrounding tissues to form new bone. Inconsistent induction potential in commercially available allogenic grafting materials may be partly responsible for the variability in study results on osseous grafts. Continuing refinements such as these will ultimately improve the predictability of results.

 

再有，一些制造商已经开始单独测试供体材料了，例如用组织库的同种异体移植体，测定移植体在实验室动物体内一般不能成骨的区域，诱导骨形成的能力。这实际上增加了移植体诱导周围组织形成新骨的可能性。市面上的异体移植材料诱导的潜力不同，可能是造成骨移植研究结果多变的原因。移植材料若能持续改进，将最终改善结果的可预测性。

 

 

 

 

The search for the "perfect" grafting material has focused on bone and bone substitutes, and more recently has added biologic modifiers; that is, substances which influence the activity of the cells responsible for new periodontal ligament formation. Autogenous bone grafts are the "gold standard" for comparing the success of other graft materials. The table below shows the three categories of non-autogenous materials now being used in periodontics, with major examples of each within the category. It is obvious that the choice of material, or combination or materials, is becoming increasingly complex. We want to inform you of these materials so you may share the wide variety of possibilities with your patients.

 

对“完美”移植材料的寻找已经集中到骨和骨组织替代品上；最近还增加了生物改性剂，这种物质可以影响牙周韧带成型细胞的活性。自体骨移植术后情况，是其他移植材料需要参考的“金标准”。下面的表格是当今用于牙周病治疗的三大类非自体骨材料，每一类都有较多的实例。显而易见，对材料的选择(无论是化合产品，还是原料)变得越来越复杂。我们将这些材料信息介绍给您，当您与病人沟通时，可以有更多的选择空间。

For Periodontal Defects—Bone Substitutes

• Regenafil (RTI) Grafton get
• Bio-Oss, Osteograf-N (bovine bone skeleton)
• PerioGlas Biogran (synthetic mineral sources)

用于牙周缺损——骨替代品

•  Regenafil (RTI) Grafton get
• Bio-Oss, Osteograf-N(牛骨骨架)
• PerioGlas Biogran(合成矿物源)

 

For Periodontal Defects—Biologic Modifiers

• Emdogain (enamel matrix derivative)
• Pep-Gen (cell-binding peptide)
• PDGF (platelet-derived growth factor)

 

用于牙周缺损——生物改性剂

      Emdogain(釉质基质衍生物)

            Pep-Gen(细胞结合肽)

            PDGF(血小板衍生生长因子)

 

For Ridge Augmentation—Bone Substitutes

• DFDBA, FDBA (bone allografts)
• Regenaform, Regenafil, Grafton Putty, Flex
• Bio-Oss cortical block

 

用于牙槽嵴增高术——骨替代品

l        DFDBA, FDBA(骨同种异体移植物)

l        Regenaform, Regenafil, Grafton Putty, Flex

l        Bio-Oss 皮质块

 

 

 

For periodontal defects bone substitutes are either specialized forms of DFDBA (decalcified freeze dried bone allograft), other animal forms (xenografts) or synthetic substitutes. The specialized forms of DFDBA presently marketed for periodontal defects are Grafton gel and Regeneration Technologies Regenafil paste. Both materials have excellent retention within the surgically debrided defect, more than conventional materials. Grafton uses glycerol, a water-soluble base, as a vehicle to carry DFDBA and is about 50% DFDBA after placement.

 

用于牙周缺损的骨替代品不是特化形式的DFDBA(脱钙冻干异体骨)，就是其他的动物骨(异种移植物)或合成替代品。目前市面上销售的用于牙周缺损的特化DFDBA是Grafton凝胶和 Regeneration Technologies Regenafil 糊剂。两种材料可以很好的作用于手术清创缺损区，有效剂量多于传统材料。Grafton使用甘油(一种水溶性基质)作为DFDBA的载体，放置后，大约会有50%DFDBA作用于缺损区。

 

Grafton uses a random lot testing to insure that the DFDBA incorporated is osteoinductive. Regenafil (RTI) is 80% bone by volume after implantation as its vehicle is a gelatin, which results in less water absorption during the grafting process. Regenafil comes refrigerated, needs to be warmed prior to placement and solidifies as it cools. The liquid-solid temperature range is very narrow. Above 102-103 degrees it is a liquid/gel and at body temperature it is a solid. RTI tests each batch of materials for its osteoblastic induction potential. On an induction scale of 1-4, all RTI materials must be at least a 2.

 

Grafton采用随机抽样测试，确保含有的DFDBA具有骨诱导性。Regenafil (RTI)在植入后，其体积的80%会参与成骨过程。这是因为它的载体是一种甘油，在移植过程中吸收的水很少。Regenafil为冷冻储藏，在放置前需要加热，冷却时为凝固状态。固液态间温度变化范围很狭，在102-103度为液体/凝胶，而在体温下是固体。RTI会对每一批材料的成骨诱导潜力进行测试。在诱导等级1-4中，所有的RTI材料至少需要达到2级水平。

 

The currently available animal derived periodontal defect grafting materials are Bio-Oss, Osteograf-N, Interpore 200 and Biocoral. Biocoral is calcium carbonate derived from natural coral, is resorbable and biocompatible. Bio-Oss is bovine bone from which all the organic material has been extracted, yielding a micro-porous structure very similar to autogenous bone in its chemical composition and microstructure. Osteograf-N is also a bovine bone, but with a crystalline structure rather than a microporous structure. Synthetic bone substitutes include bioactive glasses (Perioglass and Biogran) and a porous methylmethacrylate (HTR). HTR has been shown to increase bone apposition only when in close contact to adjoining bone, such as along an extraction socket wall. The bioactive glasses are particulate materials, slowly resorb and when mixed with fluids in a periodontal defect form an adherent surface layer of silicon, calcium, flouride and sodium that binds the graft to bone. They obliterate defects well, are not inductive of bone formation, but conduct mineralization by promoting absorption and concentration of proteins used by osteoblasts to form the extracellular matrix of bone.

 

当前可用的动物源性牙周缺损移植材料是Bio-Oss、Osteograf-N、Interpore 200 和 Biocoral。Biocoral是源于天然珊瑚的碳酸钙，具有可吸收性和生物相容性。Bio-Oss源于牛骨，所有的有机物质已经从中提出，在化学结构和微型结构上与自体骨的微孔结构非常相似。Osteograf-N同样源于牛骨，但是具有的是一种晶体结构而非微孔结构。合成骨替代品包括生物活性玻璃(Perioglass 和 Biogran)和一种多孔甲基丙烯酸甲酯(HTR)。已经证明，HTR只有在亲密接触其周围骨组织时才会提高骨附着能力，如沿拔牙后的牙槽窝壁放置。生物活性玻璃是颗粒状物质，吸收缓慢，在牙周缺损区与液体混合后可形成硅、钙、氟、钠的粘结表层，这个表层能将移植物固定到骨组织上。这种材料可以很好的消除缺损，不是由骨形成诱导的，而是通过促进被成骨细胞利用的蛋白质的吸收和浓缩，引导矿化，形成细胞外骨基质。

 

The key characteristics being sought in these materials are the ability to adhere to the defect, encourage clot formation and rapid vascularization, and provide a physical scaffold along with the minerals needed for bone formation. In the case of DFDBA and autogenous bone, components of the graft act to induce osteoblastic transformation and proliferation. It is the nature of these inducing agents within bone grafts that have led researchers to search for the biologic modifiers in grafts that encourage defect repair. The three most common biologic modifiers today are Emdogain, Pep-Gen and PDGF.

 

这些材料的主要特点是具有粘附到缺损部位的能力，促使血凝块形成并迅速血管化，并提供物理支架和骨形成所需的矿物质。在用DFDBA和自体骨治疗时，移植物扮演了诱导成骨细胞转化和增殖的角色。就是这些骨移植物中具有诱导剂性质的成分，指引着研究者去寻找移植物中可以促进缺损修复的生物改性剂。当今最常见的三种生物改性剂是Emdogain、Pep-Gen和PDGF。

 

Emdogain is an enamel matrix, protein-rich gel extracted from pig tooth buds. Enamel matrix protein is secreted by Hertwig's epithelial root sheath and is responsible for initiating the original formation of acellular cementum on the developing tooth root. In periodontal defects the rationale for its use suggests that host PDL cells/fibroblasts will be transformed into cementoblasts and begin forming new attachments of connective tissue to the root surface. These enamel matrix proteins when suspended in a thickening agent (propylene glycol alginate - PGA) are retained on root surfaces for up to two weeks. The enamel matrix derivative has also been demonstrated by Gestrelius et al to retard downgrowth of epithelium. In the ten clinical studies of this material published since 1997, including two human histological cases reported, attachment level gains have been compatible to guided tissue regeneration membranes. By comparison of similar studies Emdogain appears to produce results similar to DFDBA. Autogenous bone remains the "gold standard" for regeneration studies.

 

Emdogain是一种富含釉质基质蛋白的凝胶，从猪的牙蕾中提取。釉质基质蛋白由Hertwig’s上皮根鞘分泌，能诱导发育牙根上的非细胞牙骨质的初期成形。在牙周缺损中，该材料的作用机理是宿主PDL细胞/成纤维细胞可以转化为成牙骨质细胞，并形成新的结缔组织，从而附着到牙根表面。当材料悬浮于增稠剂(海藻酸丙二醇酯)时，这些釉质基质蛋白可以在牙根表面滞留长达两周。该釉质基质衍生物也被Gestrelius等证明可以延缓上皮向下生长。1997年以来出版的十篇关于该材料的临床研究中(包括两份人类组织学病例)，治疗后所获得的附着水平已经能与引导组织再生膜相适应了。通过与类似研究进行比较，Emdogain治疗后的结果似乎与DFDBA相似。自体骨植入结果，仍然是再生研究的“金标准”。

 

 

 

 

 

 

Pep-Gen is a synthetic amino acid sequence identical to that found in the non-allogenic portion of the collagen molecule. The material is combined with an anorganic microporous bovine bone. The portion of collagen protein incorporated in the graft is thought to be responsible for binding fibroblasts and osteoblasts in the material matrix. Yukna, in a histologic study of four human specimens, showed two of the four specimens had new periodontal attachment over previously diseased root surfaces. In the only clinical study to date, Yukna et al found greater defect fill in Pep-Gen treated defects but no greater gain in attachment levels compared to DFDBA.

 

Pep-Gen是一种合成的氨基酸序列，与异体胶原蛋白分子中发现的序列相同。该材料与在一个无机的微孔牛骨相结合。研究表明，移植物中的胶原蛋白部分与材料基质中的成纤维细胞和成骨细胞的结合密切相关。Yukna对四个人类样本的组织学研究中，发现其中的两个样本在原先的病变牙根表面上有新的牙周附着。在至今唯一的临床研究中，Yukna等人发现，用Pep-Gen治疗后的缺损会获得良好的充填充填效果，但是与DFDBA相比，没有获得更佳的附着水平。

 

The most recent biologic modifier is platelet derived growth factor (PDGF). Since this material is derived from the patient's own platelet rich plasma it is not a commercial preparation. Marx et al have described this process. One hundred and fifty milliliters of whole blood is drawn into a citrated container. The platelet rich plasma is separated using a platelet separator, like a centrifuge, and it is added to autogenous or allogenic bovine bone. After placement of the graft material-enriched PDGF, a coat of PRP plasma is placed over the graft area and the flaps closed.

 

当今最先进的生物改性剂是血小板源性生长因子(PDGF)。因这种材料源于病人自身富含血小板的血浆，所以不是一种商业制剂。Mart等人对这个过程进行了描述：150毫升全血被吸入枸橼酸容器。用血小板分离器(如离心机)分离富含血小板的血浆，然后加入自体骨或异体牛骨。在富含PDGF的移植材料放置好后，将PRP血浆膜覆盖在移植区并关闭瓣膜。

 

In Marx's study of mandibular defects, both the amount and rate of bone formation were increased. This could be particularly significant for patients whose bone formation is reduced such as the elderly, those with diabetes or osteoporosis. Platelet rich plasma is high in concentration of three growth factors: PDGF (platelet derived growth factor), TGF-B (transforming growth factor beta) and IGF (insulin-like growth factor). The spin down process of platelets increases the concentration by 300%. PRP/PDGF is just beginning to receive clinical utilization.

 

在Marx的下颌骨缺损的研究中，骨成形的量和速率都有所增加。这尤其是适合那些因年龄过大、患有糖尿病或骨质疏松而骨成形减慢的病人。富含血小板的血浆中有三种高浓度的生长因子：PDGF(血小板源性生长因子)、TGF-B(转化生长因子-β)和IGF(胰岛素样生长因子)。离心之后，血小板浓度增加了300%。PRP/PDGF刚刚开始进行临床应用。