改性纳米羟基磷灰石表面性质及对成骨细胞贴壁生长的影响

背景：生物材料表面性质的改变能够影响其与细胞的相互作用,并进一步影响细胞黏附能力、基因表达等行为。 目的：评价改性纳米羟基磷灰石的表面性质及其对成骨细胞在材料表面黏附能力的影响。 方法：参考作者既往实验制备纳米羟基磷灰石和改性纳米羟基磷灰石,利用zeta电位仪测定改性纳米羟基磷灰石的zeta电位,通过测定水在改性羟基磷灰石表面的接触角,结合成骨细胞黏附试验,分析表面改性对材料的细胞黏附能力和生物相容性的影响。 结果与结论：改性纳米羟基磷灰石表面呈疏水性,接触角为93°,成骨细胞黏附实验表明,改性纳米羟基磷灰石表面比纳米羟基磷灰石表面黏附更多的成骨细胞,表明表面改性增强了纳米羟基磷灰石的生物相容性。     

纯钛表面阳极氧化增强成骨细胞生物活性及护骨素基因的表达

背景:纯钛阳极氧化改性后形成的纳米结构与骨组织具有良好的生物相容性。目的:观察纯钛表面纳米孔结构的形貌和物相构成,以及其对MC3T3-E1小鼠前成骨细胞增殖、黏附等生物学行为和促成骨基因护骨素表达的影响。方法:取纯钛片24份,其中12份仅进行机械抛光,作为对照组;另外12份进行机械抛光后,应用阳极氧化技术在纯钛表面制备纳米孔结构,作为实验组。将小鼠前成骨细胞MC3T3-E1分别接种于两组试件表面,接种7 d后扫描电镜下观察细胞形态,采用MTT法检测细胞增殖情况,绘制生长曲线;同时检测细胞促成骨基因护骨素的表达。结果与结论:阳极氧化后钛片表面形成规格统一的纳米孔结构,但是物相构成并未发生变化。与接种于对照组试件上的成骨细胞相比,实验组试件表面的细胞密度变大,覆盖金属的面积更多,呈现多边形结构,突触向周围移行,可见板状伪足向周围材料伸出;接种第7天时,实验组细胞数目约为对照组的1.4倍,同时纳米孔表面成骨细胞护骨素基因的表达高于对照组(P0.01)。结果表明阳极氧化后形成纳米孔结构的钛片更有利于成骨细胞的黏附、增殖和护骨素基因的表达,进而促进成骨细胞生长,具有良好的生物相容性。     

马来酸酐改性聚乳酸对成骨细胞黏附、增殖和分化的研究

通过研究马来酸酐改性聚乳酸(MPLA)和聚乳酸(PDLLA)材料表面对MC3T3-E1成骨细胞形态、黏附、增殖、细胞总蛋白含量、碱性磷酸酶活性及细胞分泌无机钙含量的影响,评价MPLA和PDLLA材料的细胞相容性。结果显示:与PDLLA相比,MPLA材料上的成骨细胞完全黏附和充分铺展;MPLA材料上细胞的增殖速率、细胞总蛋白含量、细胞碱性磷酸酶活性及细胞分泌的无机钙含量都显著高于PDLLA(P<0.01)。这些结果说明,MPLA材料能促进MC3T3-E1成骨细胞的黏附、铺展、增殖及蛋白质的合成,并能促进成骨细胞的分化和矿化,与PDLLA材料相比具有更好的细胞相容性。     

骨修复用纳米羟基磷灰石/聚酰胺66的体内外生物相容性(英文)

背景:采用基于纳米羟基磷灰石溶胶新方法制备纳米羟基磷灰石/聚酰胺66复合材料,该材料提高了纳米羟基磷灰石在聚酰胺66基体中的均匀分布和二者的有效键合,进而有利于改善材料的生物性能,有望成为新型骨修复材料。目的:评价纳米羟基磷灰石/聚酰胺66复合材料体内外生物相容性。方法:①将原代培养的成骨细胞与纳米羟基磷灰石/聚酰胺66及聚酰胺66材料复合培养,使用倒置相差显微镜和场发射扫描电子显微镜观察材料周围及表面的细胞形态。②将纳米羟基磷灰石/聚酰胺66复合材料植入兔右侧胫骨,将聚酰胺66作为对照组材料植入兔左侧胫骨。在术后2,8周,取材料周围骨组织进行病理组织切片观察。结果与结论:①纳米羟基磷灰石/聚酰胺66和聚酰胺66未表现出明显的细胞毒性,纳米羟基磷灰石/聚酰胺66材料周围细胞形态好于聚酰胺66,且纳米羟基磷灰石/聚酰胺66表面细胞数量多于聚酰胺66,在复合培养的第3天差异尤其显著(P0.01)。②在植入早期,与纳米羟基磷灰石/聚酰胺66相接的骨组织成骨细胞活跃且该组材料周围的骨形成过程较对照组更快。结果说明纳米羟基磷灰石/聚酰胺66复合材料较聚酰胺66有更好的生物相容性。     

多肽修饰可促进心血管植入材料的内皮化

背景:将多肽类生物信息分子应用于心血管植入材料的表面修饰,人工模拟细胞外基质功能蛋白,可以促进材料的内皮化。目的:回顾近年来关于多肽修饰在心血管植入材料内皮化方面的相关研究,为相关研究提供新的实验思路。方法:应用计算机检索1990年1月至2013年12月PubMed数据库中有关多肽修饰促进材料内皮化方面的研究,检索关键词为"peptides,surface modification,endothelialization",根据纳入排除标准选择,最终选择43篇文献进行综述。结果与结论:选择来源于细胞外基质功能蛋白的短肽表面修饰各类材料,既能促进内皮细胞的黏附,也能避免直接引入天然细胞外基质成分的缺陷。非特异性多肽主要包括RGD和YIGSR等,此类多肽均能促进包括内皮细胞在内多种细胞类型的黏附。特异性多肽主要包括REDV、CAG和SVVYGLR等,这些多肽可选择性促进内皮细胞的黏附和扩展。应用此类多肽表面修饰,可特异性促进材料的内皮化。联合应用几种多肽或联合特异性多肽与其他一些生物信息分子也许是未来应用多肽修饰促进心血管植入材料内皮化的理想方案。     

体外构建腺病毒介导骨形态发生蛋白2基因转染骨髓间充质干细胞复合纳米羟基磷灰石的植骨材料

背景:随着组织工程和基因工程技术迅速发展,基因增强的组织工程骨为临床治疗骨缺损带来美好的前景。目的:观察经腺病毒介导的人骨形态发生蛋白2表达载体(Ad-BMP-2)转染后的兔骨髓间充质干细胞在纳米羟基磷灰石植骨材料上的黏附、增殖及骨形态发生蛋白2的表达情况。方法:用Ad-BMP-2转染兔骨髓间充质干细胞,免疫组化、蛋白印迹法检测转染后细胞内骨形态发生蛋白2的表达情况。将转染48h的细胞均匀接种到纳米羟基磷灰石植骨材料上,扫描电镜观察细胞黏附状况,并采用MTT比色法测定骨髓间充质干细胞的增殖情况;消化收集黏附植骨材料上第3,5,7天的细胞,蛋白印迹检测黏附材料上细胞骨形态发生蛋白2的表达。结果与结论:转染后,骨髓间充质干细胞内骨形态发生蛋白2有高表达;扫描电镜见转染细胞在纳米羟基磷灰石材料孔隙周围及孔隙内黏附生长良好并大量增殖,MTT分析结果显示,纳米羟基磷灰石对骨髓间充质干细胞的体外增殖无抑制作用,复合后骨形态发生蛋白2有较高表达。结果表明经Ad-BMP-2转染后的骨髓间充质干细胞与纳米羟基磷灰石植骨材料生物相容性好,细胞在材料上能稳定长效地分泌骨形态发生蛋白2。     

聚合物表面生物修饰对肌腱细胞黏附特性的影响

为了探讨增强肌腱细胞与聚合物材料黏附力学特性的措施 ,采用生物可降解聚合物—乳酸与羟基乙酸共聚物 85 / 15 ,制成透光的薄膜 ,在膜表面裱衬聚赖氨酸的基础上 ,表面裱衬细胞外基质 ( I型胶原蛋白、纤维粘连蛋白 ,以及相应的抗体 )和生长因子 (类胰岛素生长因子 1) ,接种转化人胚肌腱细胞后 ,利用微吸管实验技术测定转化人胚肌腱细胞与聚合物薄膜的黏附力。结果显示 :在聚合物薄膜表面裱衬纤维粘连蛋白或 I型胶原蛋白 ,可明显提高转化人胚肌腱细胞与聚合物薄膜的黏附力 ( P<0 .0 5 ) ,但若在此基础上进一步分别复合裱衬纤维粘连蛋白抗体或 I型胶原蛋白抗体 ,则引起转化人胚肌腱细胞与聚合物薄膜的黏附力明显下降 ( P<0 .0 5 ) ;肌腱细胞对聚合物薄膜的黏附力与细胞外基质蛋白 (纤维粘连蛋白或 I型胶原蛋白 )的裱衬浓度有很好的依赖性 ;I型胶原蛋白和纤维粘连蛋白介导转化人胚肌腱细胞与聚合物薄膜的特异性黏附作用 ;二者复合裱衬浓度达到一定比例时 ,可产生协同作用 ,增强黏附效果 ;这种特异性黏附作用可被相应的抗体分子所抑制 ;生长因子对转化人胚肌腱细胞有明显的促黏附作用。提示 ,材料表面生物修饰可促进转化人胚肌腱细胞与聚合物的黏附作用 ,这对构建组织工程化肌腱具有重要的指导意义     

成骨细胞在生物活性材料中黏附性能研究进展

成骨细胞与骨基质材料间的相互作用是骨组织工程研究的主要领域,其中细胞与材料的黏附是基础,细胞必须与材料发生适当的黏附,才能进行迁移、增殖和分化。综述了与成骨细胞黏附有关的蛋白质、生物活性复合材料的表面特征和表面修饰对成骨细胞黏附性能的影响,为骨组织工程的研究提供一定的依据,尤其为组织工程新材料的研制提供参考。     

骨髓基质干细胞复合煅烧骨的皮下成骨

背景：研究证明骨髓基质干细胞与煅烧骨支架材料结合后可形成组织工程化骨,但在动物体内的生物相容性及皮下诱导成骨的能力国内报道较少。 目的：观察骨髓基质细胞复合异种煅烧骨植入BALB/c裸鼠背部皮下的成骨性能及煅烧骨材料作为组织工程骨支架材料的可行性。 方法：选用经脱脂及脱蛋白处理后高温煅烧形成的骨支架材料与梯度密度离心法分离培养至第3代的羊骨髓基质干细胞构建细胞-煅烧骨复合物植入BALB/c裸鼠背部皮下,选同期对侧背部皮下植入单纯煅烧骨为对照组。 结果与结论：煅烧后的松质骨块为白垩色,表面呈蜂窝状多孔结构,保留了天然松质骨的多孔状空间结构。骨小梁结构完整,孔隙相互连通。骨髓基质干细胞接种到煅烧骨后24 h可见大量细胞黏附于支架上,7 d后细胞分泌大量细胞外基质,细胞与基质分界不清,细胞能在材料上良好地黏附、增殖与生长,细胞活性未受到支架材料的影响。植入4周后,两组均可见煅烧骨边缘出现少量残片,细胞-煅烧骨复合物组煅烧骨孔隙周边可发现骨细胞,对照组煅烧骨表面可见纤维结缔组织包绕。植入后8周,两组均可见到煅烧骨部分降解为片状类骨质,周围有成纤维细胞包绕,排列紧密,形态多样,细胞-煅烧骨复合物组煅烧骨孔隙内可见煅烧骨表面有排列成行的成骨细胞,孔隙间有散在淋巴细胞浸润。对照组标本可见孔隙内有大量结缔组织长入,未见明显成骨迹象。结果说明,经高温煅烧后的松质骨材料,具有良好的生物相容性和生物安全性,可作为骨髓基质干细胞的良好载体,复合后植入体内能够诱导新生骨组织形成,可作为骨缺损组织工程修复的支架材料。     

尼古丁对不同表面处理种植体骨结合的影响

背景：研究证实尼古丁会影响成骨细胞、破骨细胞、成纤维细胞和红细胞的活性。 目的：检测尼古丁对表面喷砂或酸蚀处理种植体植入后骨结合及骨保护素、骨形成蛋白2表达的影响。 方法：将24只SD大鼠随机均分为实验组和对照组,实验组大鼠每天2次背部皮下注射2 mg/kg尼古丁,对照组对应皮下注射等量生理盐水。2周后在两组大鼠胫骨近干骺端分别植入表面喷砂或酸蚀处理的钛种植体,实验组继续皮下注射尼古丁,对照组注射生理盐水。种植后第2,4周对种植体及其周围骨组织行CT、X射线、荧光定量PCR及苏木精-伊红染色观察。 结果与结论：与对照组相比,实验组骨结合程度及骨保护素和骨形成蛋白2表达明显下降(P < 0.05)。在尼古丁作用下,表面喷砂处理种植体组骨保护素和骨形成蛋白2表达、表面酸蚀处理种植体组骨保护素表达均随时间变化明显下调(P < 0.05),并且表面酸蚀处理种植体组植入2周时骨形成蛋白2表达高于表面喷砂处理种植体组(P < 0.05);X射线与CT结果提示,尼古丁干预对表面酸蚀处理种植体周围新生骨形成量和新生骨矿化程度的影响明显小于表面喷砂处理种植体。苏木精-伊红染色显示,两种种植体周围成骨细胞的数量与活性随时间变化均降低,但表面酸蚀处理种植体组效果好于表面喷砂处理种植体组。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

Priming the Surface of Orthopedic Implants for Osteoblast Attachment in Bone Tissue Engineering

The development of better orthopedic implants is incessant. While current implants can function reliably in the human body for a long period of time, there are still a significant number of cases for which the implants can fail prematurely due to poor osseointegration of the implant with native bone. Increasingly, it is recognized that it is extremely important to facilitate the attachment of osteoblasts on the implant so that a proper foundation of extracellular matrix (ECM) can be laid down for the growth of new bone tissue. In order to facilitate the osseointegration of the implant, both the physical nanotopography and chemical functionalization of the implant surface have to be optimized. In this short review, however, we explore how simple chemistry procedures can be used to functionalize the surfaces of three major classes of orthopedic implants, i.e. ceramics, metals, and polymers, so that the attachment of osteoblasts on implants can be facilitated in order to promote implant osseointegration.     

Extracellular matrix-mimetic adhesive biomaterials for bone repair

Limited osseointegration of current orthopedic biomaterials contributes to the failure of implants such as arthroplasties, bone screws, and bone grafts, which present a large socioeconomic cost within the United States. These implant failures underscore the need for biomimetic approaches that modulate host cell-implant material responses to enhance implant osseointegration and bone formation. Bioinspired strategies have included functionalizing implants with extracellular matrix (ECM) proteins or ECM-derived peptides or protein fragments, which engage integrins and direct osteoblast adhesion and differentiation. This review discusses (1) bone ECM composition and key integrins implicated in osteogenic differentiation, (2) the use of implants functionalized with ECM-mimetic peptides/protein fragments, and (3) growth factor-derived peptides to promote the mechanical fixation of implants to bone and to enhance bone healing within large defects.     

An in vitro model for mineralization of human osteoblast-like cells on implant materials

An in vitro mineralizing cell-implant system was developed to study osteoblast attachment, secretion of extracellular (ECM) matrix proteins and mineralization. Saos-2 cells were plated on Tivanium (Tiv, Ti-6A1-4V), Zimaloy (Zim, Co-Cr-Mo) and glass disks. The cells were cultured in alpha-MEM medium with 10% fetal bovine serum and 50 microg ml(-1) ascorbic acid. The cultures were analyzed for calcification and for mRNA expression for ECM proteins after 1, 2, 4 and 6 weeks. Calcium content was significantly higher in cells on Tiv, less on Zim and least on glass disks. With the addition of 3 mm beta-glycerophosphate (beta-GP), the cell layer was more calcified on Zim than on Tiv and all substrates had three times more calcium than cultures without beta-GP. All subsequent experiments were performed without beta-GP. Phalloidin immunofluorescence microscopy of the actin-based cytoskeleton at 2 weeks demonstrated nodules composed of multilayered, cobblestone-appearing osteoblasts overlying calcified matrix which was stained with calcein. On Tiv, calcified nodules were connected in a trabecular-like pattern while on Zim, calcification was dispersed throughout the cell layer. Northern blots for alkaline phosphatase, bone sialoprotein, osteocalcin and alpha1(I) procollagen mRNAs were performed at different time points. The amount and pattern of calcification as well as the expression of ECM-mRNAs differed on each implant material. The results indicate that Tiv stimulates the production of more ECM proteins and mineralized matrix than Zim or glass in this osteoblast-like cell/implant culture.     

Synergistic effect of titanium alloy and collagen type I on cell adhesion, proliferation and differentiation of osteoblast-like cells

A number of studies have demonstrated the pivotal role of collagen in modulating cell growth and differentiation. In bone, where the extracellular matrix is composed of approximately 85% type I collagen, cellular interaction with matrix components has been shown to be important in the regulation of the osteoblast phenotype. Preservation or enhancement of normal osteoblast function and appositional bone formation after implant placement represents a strategy that can be useful for the purpose of improving osseointegration. In order to further improve biocompatibility, we combined two known favorable compounds, namely the titanium alloy, Ti6A14V, with type I collagen. We assessed the in vitro behavior of primary osteoblasts grown on both fibrillar collagen-coated and tropocollagen-coated Ti6A14V in comparison with uncoated titanium alloy, using an improved adsorption procedure. As parameters of biocompatibility, a variety of processes, including cell attachment, spreading, cytoskeletal organization, focal contact formation, proliferation and expression of a differentiated phenotype, were investigated. Our results demonstrated for the first time that in comparison to uncoated titanium alloy, collagen-coated alloy enhanced spreading and resulted in a more rapid formation of focal adhesions and their associated stress fibers. Growing on collagen-coated Ti6A14V, osteoblasts had a higher proliferative capacity and the intracellular expression of osteopontin was upregulated compared to uncoated titanium alloy. Type I collagen-coated titanium alloy exhibits favorable effects on the initial adhesion and growth activities of osteoblasts, which is encouraging for its potential use as bone graft material. Moreover, collagen type I may serve as an excellent biocompatible carrier for osteotropic factors such as cell adhesion molecules (e.g. fibronectin) or bone-specific growth factors.     

重组骨脱细胞细外基复合Wistar大鼠成骨细胞体外培养的形态学观察

目的新型重组骨脱细胞细胞外基质(REAECM)的制备及其细胞相容性的初步检测,为骨组织工程寻找一种新型的细胞外支架提供实验依据。方法应用体外细胞培养技术,对鼠成骨细胞和REAECM体外进行联合培养1-4周,通过相差显微镜、光镜、电镜观察细胞在材料中的生长情况。结果成骨细胞可以在REAECM上发生良好的黏附、增殖,并且可以长入REAECM的孔隙内。结论REAECM可作为构建组织工程骨的一种较好的支架材料,具有网状孔隙结构;在体外和成骨细胞复合培养时表现出良好的细胞相容性,可以作为一种天然的骨组织替代材料。     

A functional polyester carrying free hydroxyl groups promotes the mineralization of osteoblast and human mesenchymal stem cell extracellular matrix

Functional groups can control biointerfaces and provide a simple way to make therapeutic materials. We recently reported the design and synthesis of poly(sebacoyl diglyceride) (PSeD) carrying a free hydroxyl group in its repeating unit. This paper examines the use of this polymer to promote biomineralization for application in bone tissue engineering. PSeD promoted more mineralization of extracellular matrix secreted by human mesenchymal stem cells and rat osteoblasts than poly(lactic-co-glycolic acid) (PLGA), which is currently widely used in bone tissue engineering. PSeD showed in vitro osteocompatibility and in vivo biocompatibility that matched or surpassed that of PLGA, as well as supported the attachment, proliferation and differentiation of rat osteoblasts and human mesenchymal stem cells. This demonstrates the potential of PSeD for use in bone regeneration.     

Ultrastructural characterization of the implant/bone interface of immediately loaded dental implants

Primary stability and an optimized load transfer are assumed to account for an undisturbed osseointegration process of implants. Immediate loaded newly designed titanium dental implants inserted in the mandible of minipigs were used for the characterization of the interfacial area between the implant surface and the surrounding bone tissue during the early healing phase. Histological and electron microscopical studies were performed from implant containing bone specimens. Two different load regimens were applied to investigate the load related tissue reaction. Histological and electron microscopical analysis revealed a direct bone apposition on the implant surfaces, as well as the attachment of cells and matrix proteins in the early loading phase. A striking finding of the ultrastructural immunocytochemical investigations was the synthesis and deposition of bone related proteins (osteonectin, fibronectin, fibronectin receptor) by osteoblasts from day one of bone/biomaterial interaction. Calcium-phosphate needle-like crystallites were newly synthesized in a time-related manner directly at the titanium surface. No difference in the ultrastructural appearance of the interface was found between the two loading groups. Our experimental data suggest that loading of specially designed implants can be performed immediately after insertion without disturbing the biological osseointegration process.     

纳米羟基磷灰石复合基因转染生长因子修复牙槽骨缺损

背景：研究发现成骨细胞可促进牙槽骨的形成,而血小板衍生生长因子A因子转染成骨细胞对于牙槽骨形成的作用尚不清楚。 目的：将基因转染的血小板衍生生长因子A重组质粒与纳米羟基磷灰石复合移植到骨缺损处,观察其对骨缺损修复的影响。 方法：将24只新西兰大白兔随机分成实验组与对照组,制作双侧下颌下缘10 mm×6 mm×4 mm骨质缺损,实验组植入血小板衍生生长因子A转染成骨细胞与纳米羟基磷灰石的复合材料,对照组单纯植入纳米羟基磷灰石。术后4,8,12周取材行大体标本、锥形束CT、组织学观察及扫描电镜观察。 结果与结论：术后不同时间点,实验组缺损处新骨生成,成骨细胞、骨小梁、骨陷窝及新生血管修复情况,以及材料与牙槽骨连接处的骨结合均明显优于对照组(P < 0.05)。表明血小板衍生生长因子A转染成骨细胞与纳米羟基磷灰石复合生成的新型材料,有较好的生物相容性,可加速骨组织再生,促进骨组织缺损修复。     

The potential role of human osteoblasts for periprosthetic osteolysis following exposure to wear particles

Aseptic loosening in total hip replacement is mainly caused by wear particles inducing inflammation and osteolysis. Wear can be a consequence of micromotions at the interface between implant and bone cement. Due to complex cellular interactions, different mediators (e.g. cytokines, proteinases) are released, which can promote osteolytic processes in the periprosthetic tissue followed by loosening of the implant. Furthermore, a reduced matrix synthesis and an induced apoptosis rate can be observed. The purpose of this study was to evaluate to what extent human primary osteoblasts exposed to wear particles are involved in the osteolysis. The viability, the secretion of collagen and collagenases and the variety of released cytokines after particle exposure was examined. Therefore, human osteoblasts were incubated with particles experimentally generated in the interface between hip stems with rough and smooth surface finishings as well as different material compositions (Ti-6Al-7Nb, Co-28Cr-6Mo and 316L) and bone cement mantle made of Palacos R containing zirconium oxide particles. Commercially pure titanium particles, titanium oxide, polymethylmethacrylate and particulate zirconium oxide were used as references. The results revealed distinct effects on the cytokine release of human osteoblasts towards particulate debris. Thereby, human osteoblasts released increased levels of interleukine (IL)-6 and IL-8 after treatment with metallic wear particles. The expression of VEGF was slightly induced by all particle entities at lower concentrations. Apoptotic rates were enhanced for osteoblasts exposed to all the tested particles. Furthermore, the de novo synthesis of type 1 collagen was reduced and the expression of the matrix metalloproteinase (MMP)-1 was considerably increased. However, wear particles of Co-28Cr-6Mo stems seemed to be more aggressive, whereas particles derived from stainless steel stems caused less adverse cellular reaction. Among the reference particles, which caused less altered reactions in the metabolism of osteoblasts in general, ZrO2 can be assumed as the material with the smallest cell biological effects.     

Osteocalcin enhances bone remodeling around hydroxyapatite/collagen composites

The effect of osteocalcin (OC), an extracellular bone matrix protein, on bone healing around hydroxyapatite/collagen composites was investigated. Cylindrical nanocrystalline hydroxyapatite implants of 2.5-mm diameter containing 2.5% biomimetically mineralized collagen type I were inserted press-fit into the tibial head of adult Wistar rats. To one implant group, 10 mug/g OC was added. Six specimens per group were analyzed at 2, 7, 14, 28, and 56 days. After 14 days, newly formed woven bone had reached the implant surface of the OC implants whereas a broad fibrous interface could still be observed around controls. Woven bone was formed directly around both implant groups after 28 days and had been replaced partially by lamellar bone around the OC implants only. No significant differences in total bone contact were seen between both groups after 56 days. The higher number of phagocytosing cells and osteoclasts characterized immunohistochemically with ED1, cathepsin D, and tartate-resistant alkaline phosphatase around the OC implants at the early stages of bone healing suggests an earlier onset of bone remodeling. The earlier and increased expression of bone-specific matrix proteins and multifunctional adhesion proteins (osteopontin, bone sialoprotein, CD44) at the interface around the OC implants indicates that OC may accelerate bone formation and regeneration. This study supports the observations from in vitro studies that OC activates both osteoclasts and osteoblasts during early bone formation.