摘要
在当今所有的种植体材料中，纯钛因其良好的生物相容性和机械加工性能，并历经多年临床应用的考验，成为首选的医用种植体材料。然而单纯的纯钛种植体-组织愈合时间长的缺点大大降低了临床种植的效率，为医患双方都带来了不便。为了有效的缩短种植体-骨结合所需的时间，在过去的二十年中，一系列表面处理技术相继涌现出来，如酸蚀喷砂技术，模拟体液涂层技术，钛浆喷涂技术，微弧氧化技术和羟基磷灰石涂层技术等。
目前，有研究已证实这些优化了的表面处理技术能够通过改善种植体材料的表面构型和生物活性来促进骨结合的过程。然而，关于这类改性后结构在经皮部位软组织的结合及反应情况却报道甚少。临床数据表明，15%-20%的修复重建病人会由于经皮部位的问题而造成感染，甚至出现严重的并发症（如骨髓炎和软组织损伤等）最终导致种植失败。另有研究表明，不同的种植体表面结构对细菌的易感性不同也会造成不同的结果。因此，种植体材料表面结构处理对经皮软组织部位的反应情况和细菌的易感性也是影响种植体的成功率的重要因素之一。
课题目的
微弧氧化具有良好的生物相容性和不易剥脱等特性，在促进种植体-骨结合方面被认为是最有效的表面处理技术之一。然而在现有研究中，该处理技术对于种植体-软组织的反应情况尚无报道。由于经皮种植体植入过程是要穿经机体软组织再锚定在骨组织上，种植体-软组织的结合面是种植体与外界的屏障，也是影响种植体成败的一个关键因素。为了评估微弧氧化纯钛种植体经皮部位的生物学性能，我们首先对三种常见的种植体表面处理技术：喷砂，微弧氧化以及模拟体液涂层在细菌的易感性方面做了横向对比研究；其次，对微弧氧化纯钛种植体表面做了进一步的深入研究，实验观察了人表皮细胞以及金黄色葡萄球菌在微弧氧化处理及未处理纯钛表面的生物学行为；再次，针对现有的微弧氧化处理对皮肤软组织表面常见菌群的易感情况，对其表面做了进一步的优化处理以改善其抗菌性能；最后，动物实验对经皮种植体软组织炎进行了初步研究。本课题研究通过对微弧氧化纯钛种植体与软组织的结合界面的评估，致力于有效提高该处理技术在种植体软组织结合界面的生物相容性和抗菌性能。
实验方法和结果
本研究首先观测了金黄色葡萄球菌在喷砂，微弧氧化和模拟体液涂层三种种植体处理表面的粘附情况，最终结果表明微弧氧化和模拟体液涂层较未处理纯钛表面更易粘附细菌。细菌计数结果证实了金黄色葡萄球菌在喷砂和微弧氧化表面的分布情况无显著差异。但是在模拟体液涂层表面金葡菌的分布较其他两组涂层表面有明显的增多。此外，三组处理表面的粗糙度较未处理纯钛表面要明显增大。有文献报道，根据材料表面结构特征，可以将表面形态的粗糙度分为三个水平：宏观级，微观级和纳米级。其中，表面粗糙度在1-10μm的定义为微观形态，喷砂，微弧氧化和模拟体液涂层的表面形态均可归类于微观级。较宏观级和纳米级形态以及具有光滑表面而言，表面粗糙度在微观级水平可以形成更好的种植体-骨结合和更高的抗扭距性能。然而，伴随着表面粗糙度的增加，一个新增的风险是随之提高了种植体周围炎的几率。我们的研究表明，随着粗糙度的增加，细菌的粘附率也有所增加，这可能与粗糙表面某种意义上增加了材料的表面面积有关。
关于XRD的实验结果，喷砂表面散射能谱显示有少量的Al2O3残留，通常情况下，喷砂粒子常常会埋藏于种植体基底材料表面。由于其不溶于酸，因此很难从钛表面彻底清除，甚至在超声清洗，酸钝化以及消毒后，仍会有少量残留。对于喷砂表面铝残留的问题不同的学者所持观点不一，有研究称残留在种植体材料表面的铝化合物会影响细菌的粘附；但也有研究称在影响细菌粘附方面，铝化合物没有显著作用。在本研究中，表面原子成分分析显示在喷砂表面有非常少量的铝残留，然而，细菌在该涂层上的粘附并没有因此而减少。
其次，实验检测了人表皮细胞和金黄色葡萄球菌在微弧氧化及未处理纯钛表面的生物学行为来反映两组材料作为种植体经皮软组织部位的生物相容性，结果表明微弧氧化表面并不能更好的支持人表皮细胞的生长，铺展，粘附和增殖；此外，微弧氧化表面更易于金葡菌的粘附和繁殖。实验数据表明，纯钛表面进行现有的微弧氧化处理作为种植体经皮部位的处理并不是一个很好的选择。从细胞在两组材料表面粘附的计数结果表明人表皮细胞在未处理纯钛表面粘附和增殖的情况更好，随着时间推移细胞生长的速度更快。
有文献报道细胞胞间接触会促进细胞的铺展，但是这一现象并未在微弧氧化表面得到证实，微弧氧化表面反而在某种程度上阻碍了人表皮细胞的生长。扫描电镜图像显示细胞在未处理纯钛表面表现出了更好的铺展，并展示出了更为清晰的胞间接触和核仁结构，而在微弧氧化的表面细胞胞体小而成梭形，这些结果表明人表皮细胞在未处理纯钛表面保持了更有活力的状态。此外，扫描电镜图也更直观地证实了这一结果，细胞在未处理纯钛表面多呈两个或多个簇状分布，而在微弧氧化表面人表皮细胞则多为孤立散在分布。总之，计数结果和电镜结果都表明在未处理纯钛表面人表皮细胞的生长，粘附和增殖相对更好，而在微弧氧化的纯钛表面人表皮细胞的生长和增殖在某种程度上受到了抑制。
同时，扫描电镜和细菌的计数结果显示，随着时间的推移，金黄色葡萄球菌的粘附和繁殖在微弧氧化的表面有明显的增加，具有统计学意义；而在未处理纯钛表面细菌增殖不明显。尤其在24h,金黄色葡萄球菌在微弧氧化表面几乎融合，表明细菌更进一步地繁殖并粘附，将要形成一层菌膜。有研究表明金黄色葡萄球菌粘附于金属表面后，经过进一步大量的繁殖会形成一层生物膜，而这层生物膜一旦形成后，临床上便很难处理。原因主要是由于这层生物膜可以保护细菌免于被吞噬并阻止抗生素对其破坏，这就提示我们要防止这层生物膜的形成，就要从最初采取措施来预防细菌的粘附。其中一个有效的办法就是采用具有抗菌功能的涂层（如抗菌剂或是阻抗蛋白附着的涂层等）来处理种植体材料表面。另外，实验中还发现一个有趣的现象就是细菌喜欢在微弧氧化孔状结构中增殖并堆积，但这些位置结构不易进入且不易清理；此外，尽管未涂层的纯钛表面比较光滑，细菌粘附较少，但也偶有缺陷或是粗糙的微小缝隙，这些也成了细菌容易粘附滋生的地带。本研究所得数据以及扫描电镜结果支持了“粗糙表面由于增加了表面面积而促进了细菌的粘附”这一观点。
随后，体外实验研究了NaCl渗透的微弧氧化处理的纯钛表面在抵抗细菌粘附方面的作用。实验结果表明NaCl渗透的微弧氧化表面显著的抑制了金黄色葡萄球菌的粘附和增殖。计数结果显示，在细菌接种至试件最初的2h和4h，NaCl渗透的微弧氧化表面较单纯的微弧氧化表面所粘附的细菌数目虽少，但没有显著的统计学差异。随着时间的推移，NaCl渗透的微弧氧化表面粘附的金葡菌数于24h计数时，已显著少于单纯的微弧氧化表面，具有统计学意义。扫描电镜照片进一步直观的印证了这一结果。
微弧氧化表面涂层了NaCl后，表面的粗糙度有轻微的增加，但是两组没有显著的统计学差异(p>0.05)。因此，推测在两组试件表面粗糙度方面这一微小的变化应该不会对细菌粘附产生显著的影响。在类似的研究中，学者Ewald提出一旦将具有NaCl涂层的种植体植入体内后，该涂层在机体内将被缓慢的洗刷掉，这样种植体表面就能够与细胞直接接触以促进结合。此外，先前研究表明高亲水性材料与体液，细胞以及组织有较强的亲和力，所以高亲水表面更合乎需要。当前研究表明NaCl渗透的微弧氧化表面较单纯的微弧氧化表面具有更高的亲水性，那么这种表面可能会对机体细胞表现出更好的生物相容性。
最后，动物实验观察了经皮种植体植入整个过程（2m）中，种植体周围软组织的反应情况以及炎症种植体周菌群的变化。细菌学检测发现炎性分泌物中以金黄色葡萄球菌和G群链球菌感染为主。此外，研究还发现，在感染早期，细菌检测结果以金葡菌为主要感染菌，而在后期，G群链球菌比例上升，金葡菌比例下降，分析可能是由于大量的G群链球菌分泌的溶葡萄菌素酶造成，这个问题还有待进一步的研究。通过对种植体经皮部位软组织反应的观察发现，单纯的微弧氧化处理的纯钛种植体出现经皮软组织炎症情况较重(p <0.05)；而NaCl浸润的微弧氧化纯钛种植体与未处理纯钛种植体的软组织反应情况较好，两者无统计学差异(p>0.05)。
结论
现有的微弧氧化技术处理的纯钛表面不能更好的支持人表皮细胞的生长和增殖；微弧氧化表面更易于金葡菌的粘附和繁殖。横向对比研究显示喷砂，微弧氧化以及模拟体液涂层较纯钛表面更易粘附细菌，而在三组涂层结构表面，模拟体液涂层对细菌易感性更为显著，微弧氧化虽然较喷砂表面在粘附细菌总数上有所减少，但无明显的统计学差异(p>0.05)。
经过对原有的微弧氧化技术参数进行优化并涂层了具有抗菌性能的NaCl成分后，新获得的纯钛改性表面能够有效地预防和抑制金黄色葡萄球菌的粘附和增殖。据文献推测，该方法在提高了材料表面抗菌性能的同时，还可能成功地保留微弧氧化良好的骨结合性能。此外，由于NaCl渗透的微弧氧化纯钛表面较单纯的微弧氧化纯钛表面具有更高的亲水性，推测该表面可能会对机体细胞表现出更好的生物相容性。
动物实验表明，种植体植入后发生感染早期以金葡菌为主要感染菌；后期G群链球菌占据主导地位。通过对种植体经皮部位软组织反应的观察表明，NaCl浸润的微弧氧化纯钛种植体经皮部位表现出了较好的抗菌性能。
Among all the implant materials, pure titanium is singled for its greatbiocompatibility and mechanical properties. After its application in the clinicuse in the past decades, titanium has been selected as one of the best implantmaterials in the medical field. However, the healing time of the titaniumimplant-to-tissue integration is very inefficient, which has broughtoverwhelming troubles to the clinicians and patients. To increase the speed ofimplant-to-tissue integration efficiently, a series of surface treatment techniquescame out in the past twenty years, such as microarc oxidation (MAO),simulated body fluid (SBF), titanium plasma sprayed (TPS) etc. Literatureshave demonstrated that these surface treatments can enhance theimplant-to-tissue integration by improving the surface structure andbiocompatibility of the implant materials. Nevertheless, few researches wereconducted to investigate these surface treatments integrated to the percutaneoussites of the implants. Clinical data revealed that15%-20%rehabilitation patients suffered peri-implantitis due to the percutaneous problems, whichcould lead to osteomyelitis and soft tissue damage and even implant failure.Therefore, the reaction of percutaneous site of the implant to the body tissue isan essential factor in the implant success.
Objectives
Microarc oxidation has been considered to be one of the most effectivesurface treatments to improve the osseointegration of the implants. However,the influences of such treatment on the skin epithelium interface still gained lessattention in present literatures. Aimed at evaluating the biological properties ofthe percutaneous sites of the MAO treated titanium (MAO_Ti) implants, thebehavior of human skin epithelial cell (HSEC) and the Staphylococcus aureus(S. aureus) on the MAO_Ti and the untreated titanium (Un_Ti) surfaces wereevaluated using in vitro models. Meanwhile, the susceptibility of differentimplant surface treatments to bacterial adhesion were evaluated in across-sectional study, including Ti-based sandblasting (Ti_SB), Ti-basedmicroarc oxidation (Ti_MAO) and Ti-based simulated body fluid coating(Ti_SBF). Furthermore, to efficiently lower the risk of peri-implantitis, theMAO technique was further optimized and the surface properties wereimproved. Finally, a pilot animal experiment was conducted to investigate thesoft tissue inflammation of prcutaneous implants and further verify the effect ofNaCl impregnated MAO_Ti implants. We hope that these data can providebasic information for further clinical study on the MAO treated titaniumimplant to soft tissue integration.
Methods and Results
Firstly, the in vitro study described the visualization and quantification ofS.aureus adhering to the three Ti-based surface coatings. Overall results showedthat Ti_SB, Ti_MAO and Ti_SBF were much more susceptible to S. aureusthan Ti surfaces. Counting results confirmed that there was no statisticallysignificant difference between the amount of bacteria on Ti_SB and Ti_MAOsurfaces, while bacteria on Ti_SBF surfaces were significantly more comparedto the other two treated surfaces. Data showed that surface roughnesses of thethree Ti-based treatments were generally higher than the pure Ti group. It isreported that surface roughness can be divided into three levels depending onthe scale of the features: macro-, micro-and nano-sized topologies. Ti_SB,Ti_MAO, and Ti_SBF surface profiles can be categorized into the micro level,which is defined for topographical features as being in the roughness range of1-10μm. Numerous studies have shown that surface roughness in this rangeresulted in greater bone-to-implant contact and higher resistance to torqueremoval than other macro-/nano-types of surface topography and also titaniumimplants with smoother surfaces. However, a major risk with increase in surfaceroughness may be an increase in peri-implantitis. Our study demonstrated theview that roughening a surface can enhance bacteria adhesion due to theincrease in surface area.
In case of the XRD pattern, Ti_SB spectra showed that there still somealumina (Al2O3) existed on the SB surfaces. Al2O3, frequently used as a blastingmaterial is often embedded into the implant surface and residue remains evenafter ultrasonic cleaning, acid passivation and sterilization, as it is insoluble inacid and is thus hard to remove from the titanium surface. It is reported that thepresence of some chemicals, such as aluminium, on the surface could influence bacterial adhesion. However, surface chemical analysis in this study showed avery low concentration of aluminium after the sandblasting. Moreover, S.aureus counting results exhibited no significant less due to the existence ofremained alumina.
Secondly, the study examined the biological behavior of HSEC andS.aureus on the percutaneous site of MAO_Ti implant surface. Our resultsdemonstrated that MAO structure did not well support the growth, spreading,attachment, and proliferation of HSEC. What’s more, MAO_Ti surface wasmuch more susceptible to S. aureus. According to our data from present study,the MAO treatment seemed not a good choice for the percutaneous site ofimplant. From the growth data of cells, we can see that the attachment andproliferation of HSEC improved faster on the Un_Ti surface than on the MAOsurface with time increasing. As expected, cell contacts increased cell spreading,but surprisingly, this phenomenon cannot be found on the MAO treated surface.It seemed that MAO treated surface in some degree inhibited the growth of theHSEC. The SEM images also showed that cells were much more spread withclearer cell contacts and cell nucleus on the Un_Ti surface while on the MAOsurface cells were small and fusiform, which indicated that HSEC on the Un_Tisurface kept in a much better state of viability. Moreover, the images confirmedthat in general there were more proliferated cells in doublets and clusters on theUn_Ti surface while on the MAO treated surface almost all cells were isolatedfrom each other. Thus, both the counting results and the SEM images indicatedthat the growth, attachment and proliferation of HSEC could be betterconducted on the Un_Ti surface, while on the MAO treated surface, cell growthand proliferation seemed to be inhibited in a certain degree.
Meanwhile, the SEM images as well as the counting results of bacteria onthe MAO_Ti and Un_Ti surfaces revealed that the multiplication of the S.aureus was more obvious on the MAO treated surfaces than on the Un_Tisurface as time increased. Especially at24h, bacteria observed on the MAOtreated surfaces were almost confluent, suggesting that the bacteria furtherproliferated and attached, tending to form a layer of bacterial film. It is knownthat once S. aureus adhere to metal surfaces they form biofilms that can bedifficult to treat clinically because the bacteria are protected from phagocytosisand antibiotics, which explains the need to prevent the initial bacterial adhesion.A possible solution is to modify the implant surface by using an antimicrobialor protein-resistant coating. Furthermore, an interesting phenomenon of thestudy was that bacteria were more liable to spread and multiply in the pores ofMAO surface where were less accessible to cells. Occasionally we could alsofind, on the deficient and rough places of the Un_Ti surface, S. aureus tended toaccumulate more than the relatively flat places. These findings along with theSEM results of the MAO treated crateriform-like surface supported the viewthat roughening a surface can enhance bacteria adhesion due to the increase insurface area.
Thirdly, this in vitro study investigated the effect of10%NaClimpregnated MAO treated titanium (NaCl_MAO_Ti) surfaces on the resistanceof bacteria adherence. The results revealed that the NaCl_MAO_Ti surfacesignificantly prevented the adhesion and multiplication of S. aureus. Thecounting results revealed the changes in the number of adhered bacteria on thetwo different surfaces with time increasing, and SEM images further confirmedthe results. Although there was no statistical difference in the number of adhered bacteria between MAO_Ti and NaCl_MAO_Ti groups during the first2to4hours, the total amount of bacteria on the NaCl_MAO_Ti surface hadstarted to drop at4h time point. After24h, the number of bacteria on theNaCl_MAO_Ti surface was radically decreased compared to what on theMAO_Ti surface.
Impregnated with10%NaCl, the surface roughness of MAO_Ti slightlyincreased compared to the control group, but there was no statistical differencebetween two groups. Therefore, the subtle changes in the surface roughness oftwo types of surfaces should not significantly affect the results of the bacteriaadherence. When incubated in the bacterial culture solution, the sodiumchloride coating was dissolved. These findings were similar to those of Ewaldet al, who inferred that once inside the human body, the NaCl coating would berinsed off the implant and enable the body cells to interact with the implantsurface directly. Moreover, previous studies have shown that highly hydrophilicsurfaces were more desirable than hydrophobic ones due to their affinity tobiological fluids, cells and tissues. Our results found that the hydrophilicity ofNaCl_MAO_Ti surface was higher than the control surface, which indicatedthat the NaCl_MAO_Ti surface might display better biocompatibility to thebody cells.
Finally, the animal experiment investigated the peri-implant soft tissueinflammatory reaction and the changes of microorganisms during the wholeimplantation. It was found that S. aureus was dominant in the early stage of theinfection, while in the late infection, the proportion of G-streptococci increasedas that of S.aureus decreased. The soft tissue reaction to the three different implants showed that the MAO_Ti implants had the worst inflammation, whileNaCl impregnated MAO_Ti and Un_Ti implants were much better.Furthermore, the peri-implant soft tissue inflammatory reaction together withthe detection results of inflammatory secretion suggested that there could be acorrelation between the G-streptococci infection and the progress ofperi-implantitis.
Conclusions
Analysis of our data, taken together, MAO treated titanium surface did notwell support the growth, adhesion and proliferation of HSEC. Additionally, itwas much more susceptible to S. aureus when compared with untreatedtitanium (Un_Ti) surface. Besides, the number of S. aureus adhering to thethree Ti-based treatments was significantly more than that on the pure Tisurfaces. Such an observation revealed that the Ti_SB, Ti_MAO, and Ti_SBFsurface coatings encouraged S. aureus adhesion, and could lead to higherinfection rates in vivo, while pure Ti surface showed advantages in preventingbacterial adhesion and lowering the rate of infection. Furthermore, NaClimpregnated MAO_Ti surface may efficiently lower the risk of peri-implantitisand hopefully it could facilitate the implementation of MAO coating techniqueto the clinic trials in the near future.
Animal experiment revealed that NaCl impregnated MAO_Ti implantscould achieve a good antibiotic function. At the early stage of theperi-implantitis, S. aureus was the dominant bacteria, while at the late stage, theproportion of G-streptococci increased and became the major portion.Furthermore, the peri-implant soft tissue inflammatory reaction suggested that there could be a correlation between G-streptococci infection and the progressof peri-implantitis.
引文
1. Branemark PI, Hansson BO, Adell R, Breine U, Lindstrom J, Hallen O,Ohman A. Osseointegrated implants in the treatment of the edentulousjaw. Experience from a10-year period. Scand J Plast Reconstr SurgSuppl1977;16:1-132.
2. Branemark PI. Osseointegration and its experimental background. JProsthet Dent1983;50(3):399-410.
3. Chehroudi B, Gould TR, Brunette DM. Effects of a groovedtitanium-coated implant surface on epithelial cell behavior in vitro andin vivo. J Biomed Mater Res1989;23(9):1067-85.
4. Chehroudi B, Gould TR, Brunette DM. The role of connective tissue ininhibiting epithelial downgrowth on titanium-coated percutaneousimplants. J Biomed Mater Res1992;26(4):493-515.
5. von Recum AF. Applications and failure modes of percutaneous devices:a review. J Biomed Mater Res1984;18(4):323-36.
6. Heaney TG. A histological investigation of the influence of adultporcine gingival connective tissues in determining epithelial specificity.Arch Oral Biol1977;22(3):167-74.
7. Adell R, Lekholm U, Rockler B, Branemark PI. A15-year study ofosseointegrated implants in the treatment of the edentulous jaw. Int JOral Surg1981;10(6):387-416.
8. Van NR. Titanium: the implant material of today. J Mater Res.1987;22:3801-3811.
9. Caplanis N, Kan JY, Lozada JL. Osseointegration: contemporaryconcepts and treatment. J Calif Dent Assoc1997;25(12):843-51.
10. Van TB, Brown SD, Wirtz GP. Mechanism of anodic spark deposition.Am. Ceram. Soc. Bull1977;56:563-566.
11. Yang C, Meng L, Tian Y, Huang T, Li Y. Cytotoxicity study of a novelimplant material modified by microarc oxidation. J Huazhong Univ SciTechnolog Med Sci2006;26(6):720-2.
12. Ma W, Wei JH, Li YZ, Wang XM, Shi HY, Tsutsumi S, Li DH.Histological evaluation and surface componential analysis of modifiedmicro-arc oxidation-treated titanium implants. J Biomed Mater Res BAppl Biomater2008;86(1):162-9.
13. Abu-Serriah M, Mcgowan DA, Moos KF, Bagg J. Extra-oralcraniofacial endosseous implant-retained prostheses. Int J OralMaxillofac Implants2003;32:452-458.
14. Gitto CA, Plata WG, Schaaf NG. Evaluation of the peri-implantepithelial tissue of percutaneous implant abutments supportingmaxillofacial prostheses. Int J Oral Maxillofac Implants1994;9(2):197-206.
15. Holgers KM, Tjellstrom A, Bjursten LM, Erlandsson BE. Soft tissuereactions around percutaneous implants: a clinical study of soft tissueconditions around skin-penetrating titanium implants for bone-anchoredhearing aids. Am J Otol1988;9(1):56-9.
16. Branemark PI. Vital microscopy of bone marrow in rabbit. Scand J ClinLab Invest1959;11Supp38:1-82.
17. Branemark PI, Breine U. Formation of Bone Marrow in IsolatedSegment of Rib Periosteum in Rabbit and Dog. Blut1964;10:236-52.
18. Branemark PI, Adell R, Breine U, Hansson BO, Lindstrom J, Ohlsson A.Intra-osseous anchorage of dental prostheses. I. Experimental studies.Scand J Plast Reconstr Surg1969;3(2):81-100.
19. Branemark PI, Albrektsson T. Titanium implants permanentlypenetrating human skin. Scand J Plast Reconstr Surg1982;16(1):17-21.
20. Branemark R, Branemark PI, Rydevik B, Myers RR. Osseointegrationin skeletal reconstruction and rehabilitation: a review. J Rehabil ResDev2001;38(2):175-81.
21. Tolman DE, Desjardins RP. Extraoral application of osseointegratedimplants. J Oral Maxillofac Surg1991;49(1):33-45.
22. Kawahara H, Kawahara D, Mimura Y, Takashima Y, Ong JL.Morphologic studies on the biologic seal of titanium dental implants.Report II. In vivo study on the defending mechanism of epithelialadhesions/attachment against invasive factors. Int J Oral MaxillofacImplants1998;13(4):465-73.
23. Jaffin RA, Berman CL. The excessive loss of Branemark fixtures intype IV bone: a5-year analysis. J Periodontol1991;62(1):2-4.
24. Urist MR. Bone: formation by autoinduction. Science1965;150(3698):893-9.
25. Urist MR, Lietze A, Mizutani H, Takagi K, Triffitt JT, Amstutz J,DeLange R, Termine J, Finerman GA. A bovine low molecular weightbone morphogenetic protein (BMP) fraction. Clin Orthop Relat Res1982(162):219-32.
26. Urist MR, Mizutani H, Conover MA, Lietze A, Finerman GA. Dentin,bone, and osteosarcoma tissue bone morphogenetic proteins. Prog ClinBiol Res1982;101:61-81.
27. Heughebaert M, LeGeros RZ, Gineste M, Guilhem A, Bonel G.Physicochemical characterization of deposits associated with HAceramics implanted in nonosseous sites. J Biomed Mater Res1988;22(3Suppl):257-68.
28. Ripamonti U. The morphogenesis of bone in replicas of poroushydroxyapatite obtained from conversion of calcium carbonateexoskeletons of coral. J Bone Joint Surg Am1991;73(5):692-703.
29. Ripamonti U. Osteoinduction in porous hydroxyapatite implanted inheterotopic sites of different animal models. Biomaterials1996;17(1):31-5.
30. Ripamonti U. Bone induction in nonhuman primates. An experimentalstudy on the baboon. Clin Orthop Relat Res1991(269):284-94.
31. Ripamonti U. The induction of bone in osteogenic composites of bonematrix and porous hydroxyapatite replicas: an experimental study on thebaboon (Papio ursinus). J Oral Maxillofac Surg1991;49(8):817-30.
32. Magan A, Ripamonti U. Geometry of porous hydroxyapatite implantsinfluences osteogenesis in baboons (Papio ursinus). J Craniofac Surg1996;7(1):71-8.
33. Ducheyne P, Cuckler JM. Bioactive ceramic prosthetic coatings. ClinOrthop Relat Res1992(276):102-14.
34. Meirelles L, Arvidsson A, Andersson M, Kjellin P, Albrektsson T,Wennerberg A. Nano hydroxyapatite structures influence early boneformation. J Biomed Mater Res A2008;87(2):299-307.
35. Meirelles L, Melin L, Peltola T, Kjellin P, Kangasniemi I, Currie F,Andersson M, Albrektsson T, Wennerberg A. Effect of hydroxyapatiteand titania nanostructures on early in vivo bone response. Clin ImplantDent Relat Res2008;10(4):245-54.
36. Schwarz F, Herten M, Sager M, Wieland M, Dard M, Becker J.Histological and immunohistochemical analysis of initial and earlyosseous integration at chemically modified and conventional SLAtitanium implants: preliminary results of a pilot study in dogs. Clin OralImplants Res2007;18(4):481-8.
37. Harris LG, Patterson LM, Bacon C, Gwynn I, Richards RG. Assessmentof the cytocompatibility of different coated titanium surfaces tofibroblasts and osteoblasts. J Biomed Mater Res A2005;73(1):12-20.
38.刘慧颖,伊哲,王学金.氟离子注入钛表面改性抗菌性能的研究.口腔医学2008;28(6):287-290.
39. Stanford CM. Surface modification of biomedical and dental implantsand the processes of inflammation, wound healing and bone formation.Int J Mol Sci;11(1):354-69.
40. Kemmenoe BH, Bullock GR. Structure analysis of sputter-coated andion-beam sputter-coated films: a comparative study. J Microsc1983;132(Pt2):153-63.
41. Ong JL, Lucas LC. Post-deposition heat treatments for ion beam sputterdeposited calcium phosphate coatings. Biomaterials1994;15(5):337-41.
42.赵宝红,自薇,崔福斋.应用IBAD方法制备纯钛表面多孔TCP／HA涂层材料的微观分析.上海口腔医学2004;13(5):385-388.
43. Jansen JA, Wolke JG, Swann S, Van der Waerden JP, de Groot K.Application of magnetron sputtering for producing ceramic coatings onimplant materials. Clin Oral Implants Res1993;4(1):28-34.
44. Lo WJ, Grant DM, Ball MD, Welsh BS, Howdle SM, Antonov EN,Bagratashvili VN, Popov VK. Physical, chemical, and biologicalcharacterization of pulsed laser deposited and plasma sputteredhydroxyapatite thin films on titanium alloy. J Biomed Mater Res2000;50(4):536-45.
45.陈传忠,王佃刚,徐萍.激光熔覆HA生物陶瓷梯度涂层的微观组织结构.中国激光2004;31(8):1021-1024.
46. Heinrich A, Dengler K, Koerner T, Haczek C, Deppe H, Stritzker B.Laser-modified titanium implants for improved cell adhesion. LasersMed Sci2008;23(1):55-8.
47. Ivanoff CJ, Hallgren C, Widmark G, Sennerby L, Wennerberg A.Histologic evaluation of the bone integration of TiO(2) blasted andturned titanium microimplants in humans. Clin Oral Implants Res2001;12(2):128-34.
48. Rasmusson L, Kahnberg KE, Tan A. Effects of implant design andsurface on bone regeneration and implant stability: an experimentalstudy in the dog mandible. Clin Implant Dent Relat Res2001;3(1):2-8.
49. Gotfredsen K, Wennerberg A, Johansson C, Skovgaard LT,Hjorting-Hansen E. Anchorage of TiO2-blasted, HA-coated, andmachined implants: an experimental study with rabbits. J Biomed MaterRes1995;29(10):1223-31.
50. Gotfredsen K, Karlsson U. A prospective5-year study of fixed partialprostheses supported by implants with machined and TiO2-blastedsurface. J Prosthodont2001;10(1):2-7.
51. Rasmusson L, Roos J, Bystedt H. A10-year follow-up study of titaniumdioxide-blasted implants. Clin Implant Dent Relat Res2005;7(1):36-42.
52. van Steenberghe D, De Mars G, Quirynen M, Jacobs R, Naert I. Aprospective split-mouth comparative study of two screw-shapedself-tapping pure titanium implant systems. Clin Oral Implants Res2000;11(3):202-9.
53. Astrand P, Engquist B, Dahlgren S, Engquist E, Feldmann H, GrondahlK. Astra Tech and Branemark System implants: a prospective5-yearcomparative study. Results after one year. Clin Implant Dent Relat Res1999;1(1):17-26.
54. Novaes AB, Jr., Souza SL, de Oliveira PT, Souza AM.Histomorphometric analysis of the bone-implant contact obtained with4different implant surface treatments placed side by side in the dogmandible. Int J Oral Maxillofac Implants2002;17(3):377-83.
55. Piatelli MJ, Doughty C, Chiles TC. Requirement for a hsp90chaperone-dependent MEK1/2-ERK pathway for B cell antigenreceptor-induced cyclin D2expression in mature B lymphocytes. J BiolChem2002;277(14):12144-50.
56. Mueller WD, Gross U, Fritz T, Voigt C, Fischer P, Berger G,Rogaschewski S, Lange KP. Evaluation of the interface between boneand titanium surfaces being blasted by aluminium oxide or bioceramicparticles. Clin Oral Implants Res2003;14(3):349-56.
57. Wong M, Eulenberger J, Schenk R, Hunziker E. Effect of surfacetopology on the osseointegration of implant materials in trabecular bone.J Biomed Mater Res1995;29(12):1567-75.
58. Cho SA, Park KT. The removal torque of titanium screw inserted inrabbit tibia treated by dual acid etching. Biomaterials2003;24(20):3611-7.
59. Park JY, Davies JE. Red blood cell and platelet interactions withtitanium implant surfaces. Clin Oral Implants Res2000;11(6):530-9.
60. Trisi P, Lazzara R, Rebaudi A, Rao W, Testori T, Porter SS.Bone-implant contact on machined and dual acid-etched surfaces after2months of healing in the human maxilla. J Periodontol2003;74(7):945-56.
61. Davies JE. Mechanisms of endosseous integration. Int J Prosthodont1998;11(5):391-401.
62. Trisi P, Lazzara R, Rao W, Rebaudi A. Bone-implant contact and bonequality: evaluation of expected and actual bone contact on machined andosseotite implant surfaces. Int J Periodontics Restorative Dent2002;22(6):535-45.
63. Trisi P, Marcato C, Todisco M. Bone-to-implant apposition withmachined and MTX microtextured implant surfaces in human sinusgrafts. Int J Periodontics Restorative Dent2003;23(5):427-37.
64. Cochran DL, Buser D, ten Bruggenkate CM, Weingart D, Taylor TM,Bernard JP, Peters F, Simpson JP. The use of reduced healing times onITI implants with a sandblasted and acid-etched (SLA) surface: earlyresults from clinical trials on ITI SLA implants. Clin Oral Implants Res2002;13(2):144-53.
65. Cochran DL, Schenk RK, Lussi A, Higginbottom FL, Buser D. Boneresponse to unloaded and loaded titanium implants with a sandblastedand acid-etched surface: a histometric study in the canine mandible. JBiomed Mater Res1998;40(1):1-11.
66. Novaes AB, Jr., Papalexiou V, Grisi MF, Souza SS, Taba M, Jr.,Kajiwara JK. Influence of implant microstructure on theosseointegration of immediate implants placed in periodontally infectedsites. A histomorphometric study in dogs. Clin Oral Implants Res2004;15(1):34-43.
67. Papalexiou V, Novaes AB, Jr., Grisi MF, Souza SS, Taba M, Jr.,Kajiwara JK. Influence of implant microstructure on the dynamics ofbone healing around immediate implants placed into periodontallyinfected sites. A confocal laser scanning microscopic study. Clin OralImplants Res2004;15(1):44-53.
68. Salemi H, Behnamghader A, Afshar A, Ardeshir M, Forati T.Biomimetic synthesis of calcium phosphate materials on alkaline-treatedtitanium. Conf Proc IEEE Eng Med Biol Soc2007;2007:5854-7.
69. Pattanayak DK, Kawai T, Matsushita T, Takadama H, Nakamura T,Kokubo T. Effect of HCl concentrations on apatite-forming ability ofNaOH-HCl-and heat-treated titanium metal. J Mater Sci Mater Med2009;20(12):2401-11.
70. Ishizawa H, Ogino M. Formation and characterization of anodictitanium oxide films containing Ca and P. J Biomed Mater Res1995;29(1):65-72.
71. Wu Y, Yu Q, Tang M, Yang B, Li H, Zhang X.[In vivo and in vitrostudies on anode-oxidized titanium percutaneous implants]. Sheng WuYi Xue Gong Cheng Xue Za Zhi2006;23(1):93-6.
72. Chung SH, Heo SJ, Koak JY, Kim SK, Lee JB, Han JS, Han CH, RhyuIC, Lee SJ. Effects of implant geometry and surface treatment onosseointegration after functional loading: a dog study. J Oral Rehabil2008;35(3):229-36.
73. Hench L, West J. The sol-gel process. Chem Rev.1990;90:33-72.
74.贺刚,陈治清,盛祖立.纯钛种植体表而纳米含氟磷灰石涂层的构建和表征中国口腔种植学杂志200712(2):51-54.
75. Rossi S, Tirri T, Paldan H, Kuntsi-Vaattovaara H, Tulamo R, Narhi T.Peri-implant tissue response to TiO2surface modified implants. ClinOral Implants Res2008;19(4):348-55.
76. Redepenning J, Schlessinger T, Burnham S, Lippiello L, Miyano J.Characterization of electrolytically prepared brushite and hydroxyapatitecoatings on orthopedic alloys. J Biomed Mater Res1996;30(3):287-94.
77. Shirkhanzadeh M. Bioactive calcium phosphate coatings prepared byelectrodeposition. J Mater Sci1991;10:19-23.
78. Meirelles L, Albrektsson T, Kjellin P, Arvidsson A, Franke-Stenport V,Andersson M, Currie F, Wennerberg A. Bone reaction to nanohydroxyapatite modified titanium implants placed in a gap-healingmodel. J Biomed Mater Res A2008;87(3):624-31.
79. Rokkum M, Reigstad A, Johansson CB. HA particles can be releasedfrom well-fixed HA-coated stems: histopathology of biopsies from20hips2-8years after implantation. Acta Orthop Scand2002;73(3):298-306.
80. Huang J, Best SM, Bonfield W, Brooks RA, Rushton N, Jayasinghe SN,Edirisinghe MJ. In vitro assessment of the biological response tonano-sized hydroxyapatite. J Mater Sci Mater Med2004;15(4):441-5.
81. Daculsi G. Biphasic calcium phosphate concept applied to artificialbone, implant coating and injectable bone substitute. Biomaterials1998;19(16):1473-8.
82.张彩珍,李运,汤玉斐.射频磁控溅射法制备羟基磷灰石/b一磷酸三钙生物涂层.生物骨材料与临床研究2008;5(2):48-50.
83. Saiz E, Goldman M, Gomez-Vega JM, Tomsia AP, Marshall GW,Marshall SJ. In vitro behavior of silicate glass coatings on Ti6A14V.Biomaterials2002;23(17):3749-56.
84.陈晓明,闫玉华,李志刚.钛合金表面涂烧生物活性玻璃陶瓷涂层的性能与结构硅酸盐学报1999;27(1):54-58.
85.贺定勇,孙旭峰,栗卓新,蒋建敏,王智慧.等离子喷涂羟基磷灰石涂层结晶度的分析.北京工业大学学报2006;32(12):1130-1133.
86. Wirtz GP, Brown SD, Kriven WM. Ceramics coatings by anodic sparkdeposition Materials Manufacting Process1991;6(1):87-115.
87. Krysmann W, Kurze P, Dittrich KH, Schneider HG. Processcharacteristics and parameters of oxidation by spark discharge (ANOF)Cryst Res Techn198419(7):973-979.
88. Li LH, Kong YM, Kim HW, Kim YW, Kim HE, Heo SJ, Koak JY.Improved biological performance of Ti implants due to surfacemodification by micro-arc oxidation. Biomaterials2004;25(14):2867-75.
89. Günterschulz N, Betz H. Neue untersuchungen per die electro-lytischeventilwirkung.. Z Physik1932;78:196-210.
90. Zhu X, Kim KH, Jeong Y. Anodic oxide films containing Ca and P oftitanium biomaterial. Biomaterials2001;22(16):2199-206.
91.邓志威,薛文斌,汪新福等.铝合金表面微弧氧化技术.材料饱和1996;29(2):15-16.
92.马臣,王颖慧,曲立杰,张向宇.钛合金微弧氧化技术的研究现状及展望中国陶瓷工业200714(1):46-49.
93. Guo Z, Zhou L, Rong M, Zhu A, Geng H. Bone response to a puretitanium implant surface modified by laser etching and microarcoxidation. Int J Oral Maxillofac Implants;25(1):130-6.
94. Chen S, Guan S, Li W, Wang H, Chen J, Wang Y. In vivo degradationand bone response of a composite coating on Mg-Zn-Ca alloy preparedby microarc oxidation and electrochemical deposition. J Biomed MaterRes B Appl Biomater.
95. Holgers KM, Thomsen P, Tjellstrom A. Persistent irritation of the softtissue around an osseointegrated titanium implant. Case report. Scand JPlast Reconstr Surg Hand Surg1994;28(3):225-30.
96. Pendegrass CJ, Goodship AE, Blunn GW. Development of a soft tissueseal around bone-anchored transcutaneous amputation prostheses.Biomaterials2006;27(23):4183-91.
97. Gristina AG. Biomaterial-centered infection: microbial adhesion versustissue integration. Science1987;237(4822):1588-95.
98. Harris LG, Richards RG. Staphylococci and implant surfaces: a review.Injury2006;37Suppl2:S3-14.
99. Quirynen M, Bollen CM. The influence of surface roughness andsurface-free energy on supra-and subgingival plaque formation in man.A review of the literature. J Clin Periodontol1995;22(1):1-14.
100. Scarano A, Piattelli M, Caputi S, Favero GA, Piattelli A. Bacterialadhesion on commercially pure titanium and zirconium oxide disks: anin vivo human study. J Periodontol2004;75(2):292-6.
101. Verheyen CC, Dhert WJ, de Blieck-Hogervorst JM, van der Reijden TJ,Petit PL, de Groot K. Adherence to a metal, polymer and composite byStaphylococcus aureus and Staphylococcus epidermidis. Biomaterials1993;14(5):383-91.
102. Donley TG, Gillette WB. Titanium endosseous implant-soft tissueinterface: a literature review. J Periodontol1991;62(2):153-60.
103. Lautenschlager EP, Monaghan P. Titanium and titanium alloys as dentalmaterials. Int Dent J1993;43(3):245-53.
104. Parreira FR, Bramwell JD, Roahen JO, Giambarresi L. Histologicalresponse to titanium endodontic endosseous implants in dogs. J Endod1996;22(4):161-4.
105. Buser D, Broggini N, Wieland M, Schenk RK, Denzer AJ, Cochran DL,Hoffmann B, Lussi A, Steinemann SG. Enhanced bone apposition to achemically modified SLA titanium surface. J Dent Res2004;83(7):529-33.
106. Le Guehennec L, Soueidan A, Layrolle P, Amouriq Y. Surfacetreatments of titanium dental implants for rapid osseointegration. DentMater2007;23(7):844-54.
107. Schwarz F, Sager M, Ferrari D, Herten M, Wieland M, Becker J. Boneregeneration in dehiscence-type defects at non-submerged andsubmerged chemically modified (SLActive) and conventional SLAtitanium implants: an immunohistochemical study in dogs. J ClinPeriodontol2008;35(1):64-75.
108. Harris LG, Tosatti S, Wieland M, Textor M, Richards RG.Staphylococcus aureus adhesion to titanium oxide surfaces coated withnon-functionalized and peptide-functionalizedpoly(L-lysine)-grafted-poly(ethylene glycol) copolymers. Biomaterials2004;25(18):4135-48.
109. Nasatzky E, Gultchin J, Schwartz Z.[The role of surface roughness inpromoting osteointegration]. Refuat Hapeh Vehashinayim2003;20(3):8-19,98.
110. Ohtsuki C, Kamitakahara M, Miyazaki T. Coating bone-like apatite ontoorganic substrates using solutions mimicking body fluid. J Tissue EngRegen Med2007;1(1):33-8.
111. Resende CX, Dille J, Platt GM, Bastos IN, Soares GA. Characterizationof coating produced on titanium surface by a designed solutioncontaining calcium and phosphate ions. Materials Chemistry andPhysics2008;109:429-435.
112. Wennerberg A, Hallgren C, Johansson C, Danelli S. Ahistomorphometric evaluation of screw-shaped implants each preparedwith two surface roughnesses. Clin Oral Implants Res1998;9(1):11-9.
113. Holgers KM, Paulsson M, Tjellstrom A, Bjursten LM, Ljungh A.Selected microbial findings in association with percutaneous titaniumimplants Int J Oral Maxillofac Impl1994;9:565-570.
114. Toljanic JA, Morello JA, Moran WJ, Panje WR, May EF. Microfloraassociated with percutaneous craniofacial implants used for the retentionof facial prostheses: a pilot study. Int J Oral Maxillofac Implants1995;10(5):578-82.
115. Lin FH, Hsu YS, Lin SH, Sun JS. The effect of Ca/P concentration andtemperature of simulated body fluid on the growth of hydroxyapatitecoating on alkali-treated316L stainless steel. Biomaterials2002;23(19):4029-38.
116. Li Y, Liu J, Shi F, Tang N, Yu L.[Preparation of hydroxyapatite coatingin concentrated simulated body fluid by accelerated biomimeticsynthesis]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi2007;24(6):1314-8.
117. Baharloo B, Textor M, Brunette DM. Substratum roughness alters thegrowth, area, and focal adhesions of epithelial cells, and their proximityto titanium surfaces. J Biomed Mater Res A2005;74(1):12-22.
118. Cranin AN, Rabkin MF, Garfinkel L. A statistical evaluation of952endosteal implants in humans. J Am Dent Assoc1977;94(2):315-20.
119. Pye AD, Lockhart DE, Dawson MP, Murray CA, Smith AJ. A review ofdental implants and infection. J Hosp Infect2009;72(2):104-10.
120. Haruyuki K, Dai K, Kimio H, Yoichiro T, Joo L. Morphologic Studieson the Biologic Seal of Titanium Dental Implants. Report I. In VitroStudy on the Epithelialization Mechanism Around the Dental ImplantInt J Oral Maxillofac Implants199813457-464.
121. Abu-Serriah MM, Bagg J, McGowan DA, Moos KF, MacKenzie D. Themicroflora associated with extra-oral endosseous craniofacial implants:a cross-sectional study. Int J Oral Maxillofac Surg2000;29(5):344-50.
122. Holgers KM, Ljungh A. Cell surface characteristics of microbiologicalisolates from human percutaneous titanium implants in the head andneck. Biomaterials1999;20(14):1319-26.
123. Holgers KM, Roupe G, Tjellstrom A, Bjursten LM. Clinical,immunological and bacteriological evaluation of adverse reactions toskin-penetrating titanium implants in the head and neck region. ContactDermatitis1992;27(1):1-7.
124. Abu-Serriah MM, McGowan DA, Moos KF, Bagg J. Extra-oralendosseous craniofacial implants: current status and futuredevelopments. Int J Oral Maxillofac Surg2003;32(5):452-8.
125. Brunette DM. Spreading and orientation of epithelial cells on groovedsubstrata. Exp Cell Res1986;167(1):203-17.
126. Brunette DM, Chehroudi B. The effects of the surface topography ofmicromachined titanium substrata on cell behavior in vitro and in vivo. JBiomech Eng1999;121(1):49-57.
127. Chehroudi B, Gould TR, Brunette DM. Titanium-coated micromachinedgrooves of different dimensions affect epithelial and connective-tissuecells differently in vivo. J Biomed Mater Res1990;24(9):1203-19.
128. Chehroudi B, Soorany E, Black N, Weston L, Brunette DM.Computer-assisted three-dimensional reconstruction of epithelial cellsattached to percutaneous implants. J Biomed Mater Res1995;29(3):371-9.
129. Harris AK, Jr. Tissue culture cells on deformable substrata:biomechanical implications. J Biomech Eng1984;106(1):19-24.
130. Huang P, Zhang Y, Xu K, Han Y. Surface modification of titaniumimplant by microarc oxidation and hydrothermal treatment. J BiomedMater Res B Appl Biomater2004;70(2):187-90.
131. Wei D, Zhou Y, Jia D, Wang Y. Characteristic and in vitro bioactivityof a microarc-oxidized TiO(2)-based coating after chemical treatment.Acta Biomater2007;3(5):817-27.
132. Yerokhin A, Nie X, Leyland A, Matthews A, Dowey SJ. Plasmaelectrolysis for surface engineering. Surf Coat Tech1999;122:73-93.
133. Nie X, Leyland A, Matthews A. Deposition of layered bioceramichydroxyapatite/TiO2coatings on titanium alloys using a hybridtechnique of micro-arc oxidation and electrophoresis. Surf Coat Tech2000;125:401-407.
134. Harris LG, Richards RG. Staphylococcus aureus adhesion to differenttreated titanium surfaces. J Mater Sci Mater Med2004;15(4):311-4.
135. Hoyle BD, Costerton JW. Bacterial resistance to antibiotics: the role ofbiofilms. Prog Drug Res1991;37:91-105.
136. Leonhardt A, Dahlen G, Renvert S. Five-year clinical, microbiological,and radiological outcome following treatment of peri-implantitis in man.J Periodontol2003;74(10):1415-22.
137. Piattelli A, Cosci F, Scarano A, Trisi P. Localized chronic suppurativebone infection as a sequel of peri-implantitis in a hydroxyapatite-coateddental implant. Biomaterials1995;16(12):917-20.
138. Norowski PA, Jr., Bumgardner JD. Biomaterial and antibiotic strategiesfor peri-implantitis: a review. J Biomed Mater Res B Appl Biomater2009;88(2):530-43.
139. Li LH, Kim HW, Lee SH, Kong YM, Kim HE. Biocompatibility oftitanium implants modified by microarc oxidation and hydroxyapatitecoating. J Biomed Mater Res A2005;73(1):48-54.
140. Lim YW, Kwon SY, Sun DH, Kim HE, Kim YS. Enhanced cellintegration to titanium alloy by surface treatment with microarcoxidation: a pilot study. Clin Orthop Relat Res2009;467(9):2251-8.
141. Wang X, Chen F, Wang G, Ma W, Zhao Y. An in vitro evaluation onthe percutaneous sites of MAO-treated implants. J Biomed Mater Res BAppl Biomater2008;87(2):508-15.
142. Wang XJ, Wang GW, Liang J. Staphylococcus aureus adhesion todifferent implant surface coatings: An in vitro study.2009.
143. Ewald A, Ihde S. Salt impregnation of implant materials. Oral Surg OralMed Oral Pathol Oral Radiol Endod2009;107(6):790-5.
144. Barth E, Myrvik QM, Wagner W, Gristina AG. In vitro and in vivocomparative colonization of Staphylococcus aureus and Staphylococcusepidermidis on orthopaedic implant materials. Biomaterials1989;10(5):325-8.
145. Petty W, Spanier S, Shuster JJ, Silverthorne C. The influence of skeletalimplants on incidence of infection. Experiments in a canine model. JBone Joint Surg Am1985;67(8):1236-44.
146. Persson GR, Roos-Jansaker AM, Lindahl C, Renvert S. Microbiologicresults after non-surgical erbium-doped:yttrium, aluminum, and garnetlaser or air-abrasive treatment of peri-implantitis: a randomized clinicaltrial. J Periodontol2011;82(9):1267-78.
147. Francois P, Vaudaux P, Foster TJ, Lew DP. Host-bacteria interactions inforeign body infections. Infect Control Hosp Epidemiol1996;17(8):514-20.
148. Herrmann M, Vaudaux PE, Pittet D, Auckenthaler R, Lew PD,Schumacher-Perdreau F, Peters G, Waldvogel FA. Fibronectin,fibrinogen, and laminin act as mediators of adherence of clinicalstaphylococcal isolates to foreign material. J Infect Dis1988;158(4):693-701.
149. Patti JM, Hook M. Microbial adhesins recognizing extracellular matrixmacromolecules. Curr Opin Cell Biol1994;6(5):752-8.
150. Elek SD. Experimental staphylococcal infections in the skin of man.Ann N Y Acad Sci1956;65(3):85-90.
151. Becker W, Becker BE, Ricci A, Bahat O, Rosenberg E, Rose LF,Handelsman M, Israelson H. A prospective multicenter clinical trialcomparing one-and two-stage titanium screw-shaped fixtures withone-stage plasma-sprayed solid-screw fixtures. Clin Implant Dent RelatRes2000;2(3):159-65.
152. Wennerberg A, Albrektsson T, Andersson B, Krol JJ. Ahistomorphometric and removal torque study of screw-shaped titaniumimplants with three different surface topographies. Clin Oral ImplantsRes1995;6(1):24-30.
153. Lew DP, Waldvogel FA. Osteomyelitis. Lancet2004;364(9431):369-79.
154. Schwartz AB, Larson EL. Antibiotic prophylaxis and postoperativecomplications after tooth extraction and implant placement: a review ofthe literature. J Dent2007;35(12):881-8.
155. Projan SJ, Bradford PA. Late stage antibacterial drugs in the clinicalpipeline. Curr Opin Microbiol2007;10(5):441-6.
156. Rice LB. Unmet medical needs in antibacterial therapy. BiochemPharmacol2006;71(7):991-5.
157. Sawase T, Hai K, Yoshida K, Baba K, Hatada R, Atsuta M.Spectroscopic studies of three osseointegrated implants. J Dent1998;26(2):119-24.
158. Scolozzi P, Jaques B. Treatment of midfacial defects using prosthesessupported by ITI dental implants. Plast Reconstr Surg2004;114(6):1395-404.