拔牙后牙槽嵴保持的研究现状
Abstract
拔牙后牙槽嵴会出现不可逆的骨吸收，常导致拔牙区骨量不足，可能会限制后期的种植或传统修复治疗，而牙槽嵴保持术可以减少拔牙后的骨量丢失。故本文从拔牙窝改建特点、影响拔牙窝的愈合因素及生物材料在牙槽嵴保持中的应用等几个方面作一综述。
Keywords: 牙槽嵴保持, 拔牙, 生物材料
Abstract
Resorption of alveolar bone that occurs following tooth extraction is irreversible, it may compromise the restoration of implants or conventional prostheses. Ridge preservation can minimize ridge resorption after tooth extraction. In this article, healing features of socket after tooth extraction, factors influencing ridge remodeling, and the use of bioma-terials were reviewed.
Keywords: ridge preservation, tooth extraction, biomaterial
拔牙会启动一系列包括软硬组织在内的修复过程，这些在拔牙窝愈合过程中有序进行的生物学事件造成了拔牙位点牙槽嵴的吸收[1]。大量研究[2]–[3]表明牙槽嵴的吸收是拔牙后的正常现象，是进行且不可逆的，直接影响术后义齿种植修复的功能及美学效果。成功的种植需要充足的骨量和有利的牙槽嵴形态，而牙槽嵴位点保存是指拔牙后软硬组织量的保存，包括牙槽窝和牙槽嵴的保存[4]。本文就牙槽嵴保存的研究现状作一综述。
1. 拔牙后牙槽嵴改建特点
1.1. 组织学特点
拔牙创愈合的组织学过程包括：血液凝集、血块机化、上皮形成、骨组织形成与改建。拔牙后即刻牙槽窝内血液充盈，血凝块形成。2~3 d，血凝块开始变为肉芽组织并在1周后被结缔组织全部取代。在第4天，上皮组织自牙槽边缘向血凝块表面生长。2~4周，网状骨和临时基质形成，并从牙槽窝冠向边缘开始矿化[5]。拔牙后的1年里都会持续牙槽窝的改建[1]。
1.2. 临床特点
拔牙后骨丢失主要发生于拔牙后的前6个月内，牙槽嵴宽度及高度可丧失达原有的50%；颊侧骨板相较于舌侧明显吸收更多，因而存在牙槽嵴舌/腭侧向位移；水平向骨丧失量多于垂直向[6]–[7]。最终，缺牙位点组织轮廓的改变造成种植修复的难度增加。
2. 影响牙槽嵴改建的因素
虽然已经证实拔牙后骨改建现象的存在，但在不同个体间其骨丧失量有差异性，目前其机制尚不清楚，但与以下因素存在相关性。
2.1. 解剖因素
Tallgren[8]发现下颌前牙的改建速度是上颌的4倍，其差异在后牙更为显著。短方脸型的牙槽骨丧失现象也更为显著。分析认为主要是咀嚼肌力直接作用而产生的现象。Cardaropoli等[9]在以48个拔牙后位点为样本，观察拔牙4个月后原有颊侧骨板厚度与拔牙窝改建颊侧骨丢失量的关系，发现原有颊侧骨板越薄，骨丢失量越多。一项研究[10]显示，与颊侧骨板厚度大于1 mm的患者相比，颊侧骨板厚度小于1 mm的患者拔牙后骨丧失量是前者的两倍，而牙周生物型与颊侧骨板厚度之间关系密切，薄的颊侧骨板往往其牙周生物型也更薄[11]。关于牙槽突的体积及骨密度与骨丧失量之间的关系，Atwood等[12]对76个人类头颅骨的测量并没有发现明显相关性。因此，在临床中可结合拔牙位点的解剖特点判断牙槽嵴保持的必要性，前牙区颊侧骨板厚度及牙周生物型对后期的美学修复至关重要，对于骨量充足的后牙区也许没有应用牙槽嵴保持手段的需要。
2.2. 手术方式
拔牙及种植过程中器械的选择、翻瓣与否以及是否初期缝合等都是需要考虑的。微创拔牙可以保护唇侧骨板的完整性，减少创伤带来的炎症反应，如Benex牵引器、种植机、超声骨刀等[13]。翻瓣对牙槽嵴保持的影响尚存在争议，Fickl等[14]观察到全厚瓣拔牙位点骨丢失更明显，而Araújo等[15]却报道翻瓣对拔牙后骨丧失量没有影响，这可能意味着翻瓣对牙槽窝愈合的影响在第6个月后消失。初期缝合的必要性尚不确定，一项Meta分析显示一期缝合有水平向骨吸收更少的趋势[16]，而另一项Meta却不认为其有差异性[17]。
2.3. 修复因素
种植体植入时机的选择对拔牙后的骨丧失量也有一定影响。即刻种植是把植体即刻植入新鲜的拔牙窝内，减少手术次数，缩短后期修复周期，且能潜在地减少拔牙后的牙槽嵴吸收[18]–[19]。但不是所有病例都适合即刻种植，故在术前就应制定好后续的修复计划，根据植入位点牙龈生物型、位点是否存在根尖周感染、位点的位置等情况进行最佳选择。
2.4. 系统因素
多项研究[20]–[22]表明年龄及性别与拔牙后的牙槽骨丧失量没有直接联系。Hong等[23]的研究发现，拔牙后的比格犬口服维生素D/Ca 4周后，与对照组相比在拔牙位点有更明显的新骨形成、更高的骨密度和更多的垂直骨量的保存。Kuroshima等[24]研究发现，拔牙后间断的甲状旁腺激素注射治疗14 d后能够明显促进拔牙窝的新骨形成。另外，亦有大鼠实验发现术后服用吲哚美辛能减少拔牙后骨丧失[25]，氟化钠虽然不能减少骨丧失但能使拔牙窝钙化更好[26]。
2.5. 其他
Ortman等[27]认为生物电刺激能通过体外脉冲电磁场减少牙槽嵴吸收。Ozkan等[28]通过大鼠实验发现吸烟会影响拔牙窝肉芽组织和骨小梁的形成。Brägger等[29]发现拔牙术后连续30 d氯己定漱口水漱口能对牙槽嵴保持起积极作用。
3. 牙槽嵴保持中生物材料的应用
在新鲜拔牙位点应用生物材料，可以提高拔牙术后伤口愈合的质量，最大化地保存骨量，为种植体的植入提供良好的机体条件。生物材料在牙槽嵴保持中的应用也是目前的研究热点。现将牙槽嵴保持中应用的生物材料分为移植材料、屏障膜、生物活性因子、复合材料四类来分别阐述其应用。
3.1. 移植材料
移植材料包括自体材料、同种异体材料、异种材料、合成材料，其原理是提供了骨形成的支架、保存了骨生长的空间、稳定血凝块以加速伤口愈合。自体骨被认为是骨再生材料的金标准，但存在着供体有限、创伤大等局限性[30]。理想的骨组织工程支架应具备以下特点：具有生物相容性，具有骨传导性和骨诱导性，降解速率与骨生长速率相匹配，成形性好以用于形状不规则的骨缺损部位，良好的力学性能，促进骨质的沉积和生长，降解产物无毒性，经济易得等[31]。
同种异体移植材料可以是新鲜冷冻骨、冻干骨和脱矿冻干骨。Borg等[32]研究发现冻干异体骨和脱矿冻干异体骨具有一定的骨诱导和骨传导作用，但存在免疫排斥、病毒感染等可能，使其应用受限。异体骨来源于牛、猪、马等，Bio-oss骨粉是将有机质从牛骨松质中去除得到的骨支架材料，Shao等[33]研究发现在种植体植入6个月后Bio-oss骨粉有很好的促骨生长作用。虽然异体骨具有生物相容性、骨引导性，但在人体中并不具有骨诱导性。合成骨架材料不需要供体，没有传播疾病的风险且可以根据需求控制材料性能。Serino等[34]从人体的随机试验中证实了，拔牙后牙槽窝中植入聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid)，PLGA]对拔牙位点的牙槽嵴保持有利。Leventis等[35]认为磷酸三钙具有良好的骨引导能力，能刺激细胞的黏附和长入，可促进组织血管化，使骨组织长入。虽然大量实验表明移植材料具有一定的牙槽嵴保持作用，但是大多数材料作用十分有限。
3.2. 屏障膜
屏障膜主要通过两种机制来帮助拔牙窝愈合。一方面隔离高增殖速率的上皮细胞、成纤维细胞等向拔牙窝内的聚集，为成骨细胞的增殖、分化提供便利。另一方面与牙槽骨壁一起阻挡软组织向拔牙窝内长入，为骨组织的形成提供空间。
屏障膜可分为可吸收和不可吸收两种。不可吸收膜有钛膜、微钛网、聚四氟乙烯膜等，Arbab等[36]在临床及组织学层面都观察到了聚四氟乙烯膜对骨形成的积极作用，且治疗过程中膜暴露时对骨性愈合无负性影响。但不可吸收膜因需手术二次取出，临床应用受限。可吸收膜包括聚乳酸膜、胶原膜等。Carmagnola等[37]发现拔牙窝应用可吸收膜后与对照组相比出现了大量的板状骨和骨髓。但可吸收膜机械强度差，对空间的维持能力欠缺，有时会出现膜移位或塌陷情况，所以需要移植材料支撑。
因此，理想的屏障膜材料应同时具备既能为硬组织形成构成空间又能被机体所降解避免二次手术的特点。
3.3. 生物活性因子
分子生物学的发展让人们逐步意识到了一些生物活性因子在拔牙窝愈合过程中的作用。在一些体内外的研究中也证实其局部应用于新鲜拔牙窝有利于细胞的趋化、增殖、分化和细胞外基质形成。
生物活性因子，如血管内皮生长因子、转化生长因子-β、甲状旁腺激素、血小板源性生长因子（platelet derived growth factor，PDGF）、重组人骨形态发生蛋白（recombinant human bone morphogentic protein，rhBMP）-2等。目前最常应用的为PDGF和rhBMP，可以促进未分化间充质细胞向成骨细胞分化形成新骨。Geurs等[38]将PDGF及富血小板血浆（platelet-rich plasma，PRP）复合支架材料应用于拔牙窝8周后，有更多的新骨形成。然而Hatakeyama等[39]比较了去血小板血浆（platelet-poor plasma，PPP）、PRP、富血小板血纤蛋白（platelet rich fibrin，PRF）对犬类拔牙窝愈合的影响，却发现PPP对牙槽嵴水平向及垂直向骨量的保存都要优于PRP和PRF，而后两者则呈现更高的骨成熟率，分析认为生长因子会不加辨别地促进任何细胞的分化且PDGF被证实会抑制成骨细胞分化。骨形态发生蛋白（bone morphogenetic protein，BMP）是目前认为相对较好的成骨因子[40]，由Urist等[41]首先发现并在兔子身上提纯获得。Coomes等[42]在39例颊侧骨板缺损超50%的拔牙病例中，发现经过rhBMP-2胶原海绵处理的拔牙窝，在影像学和临床上都呈现了更多颊侧骨板再生量和牙槽嵴保持量。虽然rhBMP能显著促进拔牙后新骨形成，但发现高剂量应用也存在一些不良反应，如伤口肿胀、皮下积液、增加癌变风险等[43]。因而也应积极寻找其他成骨因子，如Arai等[44]将肽与rhBMP结合以减少BMP剂量过大可能造成的不良反应等。
3.4. 复合材料
目前尚没有理想的单一材料应用于拔牙窝能起到很好的牙槽嵴保持作用，生物材料复合使用的研究越来越多，如支架材料的复合使用可达到更好的材料性能：PLGA具有完全的生物相容性、药物缓释的潜能，但机械强度不足，易引起无菌性炎症，而与磷酸三钙复合则能中和酸性，提高机械性能，且能调节材料降解速度，既为初期骨形成提供空间又不侵占后期骨继续形成及种植所需空间[45]–[47]。生物膜与移植材料的复合：Perelman-Karmon等[48]通过9个月的临床观察发现矿化牛骨填充的新鲜拔牙窝，用可吸收胶原膜覆盖后的伤口比对照组有更多的新骨形成；Maiorana等[49]通过多中心对照研究也得出类似的结论。支架材料与生物活性因子的复合：Shi等[50]在尖牙拔除的动物模型中，应用磷酸钙复合PRP处理拔牙窝，发现牙槽嵴高度萎缩量的明显减少。复合支架材料与多种药物的结合以达到药物缓释来减轻术后炎症、疼痛反应等多效作用[51]。
综上所述，牙槽嵴保持是必要且有效果的，目前拔牙后牙槽骨吸收的机制尚不明确，需要从临床表象总结经验走向分子水平，为牙槽嵴保持提供理论基础，而生物材料的应用是现有的最有效的牙槽嵴保持方法，因而生物组织工程学的应用也是未来的发展趋势。
Funding Statement
[基金项目] 四川省科学技术厅重点研发项目（2017SZ0094）；成都市科技局科技惠民计划项目（2016-HM01-00071-SF）
Supported by: Key Research and Development Project of Science and Technology Department in Sichuan Province (2017SZ0094); Science and Technology Benefit People Project of Science and Technology Bureau in Chengdu (2016-HM01-00071-SF).
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