伊班膦酸钠对成骨细胞分泌骨保护素的调节

背景：在正畸治疗期间,如何提高成骨速度对缩短正畸时间有很大的帮助。骨保护素能间接抑制破骨细胞成熟,加速牙周骨组织形成。 目的：观察分析局部注射伊班膦酸钠对正畸保持阶段牙周组织的影响。 方法：选取8周龄雄性SD大鼠55只,随机分为实验组、对照组、空白组。空白组直接麻醉处死。实验组和对照组均以50 g力牵引上颌右侧第一磨牙近中移动,加力21 d,然后分别于保持前1 d局部注射伊班膦酸钠和生理盐水后进入保持期,分别于保持开始后1,3,7,14,21 d,每组取5只大鼠麻醉后处死。组织经苏木精-伊红染色,免疫组织化学染色后观察。 结果与结论：苏木精-伊红染色观察见实验组破骨细胞少于对照组,相同时间的实验组与对照组比较,实验组骨保护素表达量高于对照组;实验组与对照组中,第1天与第3天骨保护素的表达量无显著性差异(P > 0.05),第7,14,21天骨保护素的表达量差异有显著性(P < 0.05)。在表达强度上,实验组骨保护素的表达呈逐渐增强的趋势,实验组与对照组骨保护素的表达均强于空白组(P < 0.05)。局部注射伊班膦酸钠能使成骨细胞分泌骨保护素增多,间接抑制破骨细胞生成,从而加速骨组织修复形成。     

局部应用唑来膦酸与纳米银对即刻种植骨结合影响的比较

背景:有研究表明局部应用唑来膦酸和局部应用纳米银都可促进骨形成,但两者效果的差异尚未见研究报道。目的:观察局部应用唑来膦酸和局部应用纳米银对兔拔牙窝即刻种植钛螺纹钉骨结合的影响差异。方法:将24只新西兰大白兔随机分为唑来膦酸和纳米银组,每组12只,在拔除兔上下颌4个切牙后,分别在2组的拔牙窝内填唑来膦酸-纳米羟基磷灰石复合物和纳米银-纳米羟基磷灰石混合物,并均同期植入钛螺纹钉。术后4,8,12周取兔上、下颌骨离体标本,通过一般形态观察、扭矩测试、骨密度检测及组织形态学观察。实验于2015年12月经河北医科大学第三医院医学伦理委员会批准(批准号:Z2015-021-1)。结果与结论:①扭矩力学实验测试结果显示,两组钛钉扭矩峰值的平均值随着时间延长而增加(扭矩峰值平均值数值),均在12周时达到最大(扭矩峰值平均值数值),术后4,8,12周,唑来膦酸组钛螺纹钉扭矩峰值平均值均略高于同期纳米银组,唑来膦酸组钛螺纹钉稳定性略优于纳米银组,但差异无显著性意义(P>0.05);②一般形态和组织学观察发现,术后4,8,12周唑来膦酸组种植体周围骨硬度和结构均明显优于同期纳米银组;③骨密度分析结果显示,术后4,8,12周,唑来膦酸组钛螺纹钉周围骨组织灰度值略高于同期纳米银组,但差异无显著性意义(P>0.05);④结果证实,从植入材料对影响种植体周围骨替代材料成骨的效果来看,用唑来膦酸纳米羟基磷灰石复合物进行即刻种植骨结合的效果略优于纳米银与纳米羟基磷灰石混合植骨。     

双膦酸盐药物长期应用对显微损伤和骨力学性能的影响

双膦酸盐类药物作为治疗骨质疏松的一线药物,可以通过降低骨转换来增加骨密度,防止骨折的发生,在临床已经有较长期应用。最近研究表明,双膦酸盐类药物在抑制骨重建的同时,会影响显微损伤的修复,导致显微损伤的积聚和骨质量的下降,进而降低骨的韧性,削弱骨的力学性能。已有临床报告指出,骨质疏松病人使用双膦酸盐后有可能发生非创伤性骨折。本文综述了双膦酸盐类药物对骨显微损伤和骨力学性能的影响。     

低功率激光对Beagle犬胫骨种植体周骨愈合的影响

背景：低功率激光照射对种植体周骨愈合及骨结合的影响尚无确切的结论。 目的：探讨低功率氦氖激光局部照射对骨内种植体周骨愈合的影响。 方法：取6只Beagle犬,每只犬两侧胫骨分别植入3枚种植体,植入后分别采用低功率氦氖激光局部照射1周,2周或不照射。分别于第4,8,12周随机处死2只Beagle犬取材。 结果与结论：亚甲基蓝-酸性品红染色显示,给予低功率氦氖激光局部照射的种植体周骨组织愈合优于未照射者。骨形态计量学分析结果显示,随着种植体植入时间的延长,种植体-骨结合率逐渐增高;在相同时间点,种植体-骨结合率以照射2周组最高,照射1周组次之。提示低功率氦氖激光局部照射能显著促进种植体周骨组织愈合及其改建成熟,同时增加种植体骨结合面积。     

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：     

局部应用伊班膦酸钠能加强内植物的早期固定：经X射线、组织学及生物力学结果验证

背景：假体内植物的无菌松动已成为假体置换后最棘手的问题。 目的：观察局部应用伊班膦酸钠对内植物早期固定作用的影响。 方法：44只新西兰大白兔,建立兔双侧胫骨近端置入金属螺钉模型,每只兔左侧局部应用质量浓度为1 mg/L伊班膦酸钠(实验组),右侧局部应用生理盐水(对照组)。 结果与结论：①X射线观察结果：造模后第2,4,8周时,实验组螺钉周围透光间隙较对照组明显变窄,且第4,8周时,实验组螺钉骨界面间新生骨较对照组明显增多。②组织学观察结果：第2周时,实验组界面间纤维膜厚度明显小于对照组(P < 0.001),第4,8周时,实验组界面间新生骨量明显高于对照组(P < 0.001)。③生物力学打出实验测试结果：第4、8周时,实验组最大剪切强度明显大于对照组(P < 0.001)。结果表明局部应用伊班膦酸钠促进早期新骨形成,增强内植物早期固定作用,从而降低中后期内植物松动的可能。     

99Tc-亚甲基二膦酸盐对胶原诱导性关节炎大鼠骨侵蚀的治疗作用

目的：观察99锝-亚甲基二膦酸盐(99technetium-methylenediphosphonate,99Tc-MDP)注射液对胶原诱导性关节炎（collagen-induced arthritis, CIA）大鼠模型骨侵蚀的治疗作用,探讨其治疗骨侵蚀的有效作用成分及可能的作用机制。方法：建立CIA大鼠关节炎模型,分为模型组、帕米膦酸二钠组、MDP组和99Tc-MDP组,关节炎指数评价关节肿胀程度;放射学评分评价骨质破坏情况;HE染色观察关节病理组织形态学变化;ELISA检测血清中核因子κB受体活化因子配体（receptor activator of NF-κB ligand,RANKL）、骨保护素（osteoprotegerin,OPG）和Dickkopf-1（DKK-1）的水平。结果：99Tc-MDP组、MDP组、帕米膦酸二钠组关节炎指数评分、骨质破坏评分均低于模型对照组（P＜0.05）;99Tc-MDP组与帕米膦酸二钠组、MDP组相比,差异有统计学意义（P＜0.05）;99Tc-MDP组、MDP组、帕米膦酸二钠组血清OPG水平高于模型组（P＜0.05）,血清RANKL和DKK-1水平低于模型组（P＜0.05）;99Tc-MDP组血清OPG水平高于帕米膦酸二钠组和MDP组（P＜0.01）,RANKL和DKK-1水平低于帕米膦酸二钠组和MDP组（P＜0.01）,但帕米膦酸二钠组和MDP组间差异无统计学意义（P＞0.05）。结论：99Tc-MDP治疗CIA大鼠骨侵蚀的有效作用成分为99Tc与亚甲基二膦酸盐两者的螯合物,并且是通过促进OPG和抑制RANKL和DKK-1的表达发挥作用的。     

非全程应用止血带对关节镜联合胫骨高位截骨术围手术期结果的影响

目的 探讨关节镜联合胫骨高位截骨术中非全程使用止血带对临床效果的影响。方法回顾性分析2018年6月至2022年1月于海南医学院第一附属医院行关节镜联合胫骨高位截骨术患者资料,根据纳入与排除标准,纳入研究72例,分为全程使用止血带组38例,仅在关节镜探查阶段使用止血带组34例,比较两组患者的围手术期指标。结果 两组患者手术时间、住院时间等无显著性差异（P>0.05）;在术后血红蛋白、红细胞压积、引流量、失血量及输血例数等方面无显著性差异（P>0.05）;非全程使用止血带组术后早期疼痛评分较低且术后第3天活动度更好（P<0.05）;非全程使用止血带组大腿疼痛发生率更低（P<0.05）;其他并发症两组患者无显著性差异（P>0.05）。结论 胫骨高位截骨术中仅在关节镜探查阶段使用止血带不会增加术后失血量、手术时间及住院时间;且可以减轻术后早期膝关节及止血带部位疼痛,有利于术后早期膝关节功能锻炼,不会增加并发症发生率。     

种植体表面处理与骨结合效应：3i种植系统的临床应用

背景：种植义齿已逐渐成为牙列缺损或缺失的常规修复方式,目前国内外采用的种植系统众多,在临床应用效果上各有特点。 目的：观察经双重酸蚀或Nano Tite表面处理的3i种植系统对牙列缺损或缺失的修复效果。 方法：95例患者植入双重酸蚀的OSSEOTITE种植体150枚(植入后1~3个月行永久修复),植入Nano Tite种植体7枚(植入后1个月行永久修复)。随访观察24个月,行临床检查及影像学检查对临床效果进行评价。 结果与结论：157枚种植体骨结合良好,种植体根周未见X射线透射区;随访期内,所有种植体均未见松动、脱落,留存率100%,成功率100%,无种植体宿主不良反应。提示经双重酸蚀或Nano Tite表面处理的种植体有利于引导成骨细胞趋化,修复效果满意。     

The effect of oxytocin on osseointegration of titanium implant in ovariectomized rats

Introduction: Oxytocin (OT) was reported to control differentiation of human mesenchymal stem cells and reverse osteoporosis (OP). This study investigated the effect of systematical treatment of OT on implant osseointegration in ovariectomized (OVX) rats. Material and methods: Twenty female rats received bilateral ovariectomy. Twelve weeks later, all animals were randomly assigned to control or experimental group. Each rat received two implants at the distal femoral metaphysis. From the first postoperative day, rats in experiment group received subcutaneous injection of OT (1 mg/kg · d), while animals in control group received vehicle. Twelve weeks after implantation, specimens containing implants were harvested and evaluated by histology, micro-CT, and push-out test. Tibiae were also harvested to evaluate the effect of OT on intact bone tissue of OVX rats. Results: Compared with control, OT treatment increased the relative bone volume surrounding the implant by 2.2 times, the percent implant osseointegration by 0.62 times, and the maximum push-out force by 2.25 times. Increased bone mass was also observed in histological sections of distal femur with implant and intact bone tissue of the proximal tibiae. Conclusion: Systemic administration of OT promoted peri-implant bone healing and osseointegration of titanium implant and recovered the negative effects of OP in undisturbed bone tissue partially.     

A new chemical etching process to improve endosseous implant osseointegration: in vitro evaluation on human osteoblast-like cells

The development of novel mechanical and chemical surface modification treatments to improve the osteointegration properties of osseointegrated dental implants is nowadays a topic of great applicative interest. The aim of the present study was to analyse the role of surface topography and chemistry of four different surface treatments on titanium by an in vitro human osteosarcoma immortalised cell line model (MG63). The surface treatments considered were (a) machined titanium, (b) chemical etched on machined titanium, (c) sandblasted titanium and (d) chemical etching on sandblasted titanium. Chemical and physical surface properties were investigated by Scanning Electron Microscopy, Thin Film-X ray Diffraction and by Laser Profilometry. The in vitro biological response was characterised using the MG63 cell line by elution cytotoxicity tests, cell morphology, adhesion, proliferation activity, alkaline phosphatase activity and total DNA content in order to show a relationship between osteoblast response and surface features. Chemical and physical characterisation showed that the considered treatments differently modify the surface morphology in the micro and sub-micrometric scale. Although some differences in alkaline phosphatase activity were observed in the biological characterisation, depending on the specific material's surface finishing, the results showed that cells were well responsive on all the tested materials and grew and differentiated with similar proliferation rate.     

Influence of implant surface topography on early osseointegration: a histological study in human jaws

The purpose of this study was to evaluate the influence of the oxidized surface on bone-to-implant contact (BIC%), the bone density in the threaded area (BA%), as well as the bone density outside the threaded area (BD%) in human jaws after 2 months of unloaded healing. Thirteen subjects (mean age 42.61 +/- 6.15 years) received two microimplants (2.5 mm diameter and 6 mm length) each, during conventional mandible or maxilla implant surgery. The microimplants with commercially pure titanium surfaces (machined) and oxidized surfaces served as the control and test surfaces, respectively. After 2 months, the microimplants and the surrounding tissue were removed and prepared for histomorphometric analysis. All microimplants, except two machined and one oxidized microimplant surfaces, were found to be clinically stable after the healing period. Histometric evaluation indicated that the mean BIC% was (21.71 +/- 13.11)% and (39.04 +/- 15.75)% for machined and oxidized microimplant surfaces, respectively. The BD% was higher for the oxidized surface, although there was no difference for maxilla and mandible. The oxidized surface impacted the BA% for the type-IV bone. Data suggest that the oxidized surface presented a higher bone-to-implant contact rate compared with machined surfaces under unloaded conditions, after a healing period of 2 months.     

Influence of extracellular matrix coatings on implant stability and osseointegration: an animal study

Aim of the present study was to test the hypothesis that the application of components of the extracellular matrix such as glycosaminoglycans used as implant surface coatings in combination with collagen, with and without growth factor, can lead to enhanced ossification and thus improve implant stability compared with collagen coatings alone. Twenty miniature pigs received 120 experimental titanium implants in the mandible. Three types of surface coatings were created: (1) collagen type I (coll), (2) collagen type I/chondroitin sulphate (coll/CS), (3) collagen type I/chondroitin sulphate/BMP-4 (coll/CS/BMP). Periimplant bone formation was assessed within a defined recess along the length axis of the implant. Bone-implant contact (BIC) and bone volume density (BVD) were determined, using both histomorphometry and synchrotron radiation micro computed tomography (SRmicroCT). To measure implant stability, resonance frequency analysis was applied after implantation and 1, 3, 7, and 22 weeks after placement. BIC was highest for coll/CS coated implants, followed by coll, p = 0.082. Histomorphometric BVD did not significantly change for any coating. SRmicroCT analysis showed an increased BVD for collagen coated implants, compared with the other two surface coatings. Implant stability showed a decrease for all coatings up to the third week. At 22 weeks, all coatings showed an increase in stability without reaching their initial level. Highest stability was reached for coll coated implants, p = 0.051. It was concluded that collagen and coll/CS implant coatings have advantageous characteristics for peri-implant bone formation, compared with the further integration of BMP-4.     

The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration

Implant osseointegration, defined as bone apposition and functional fixation, is a requisite for clinical success in orthopaedic and dental applications, many of which are restricted by implant loosening. Modification of implants to present bioactive motifs such as the RGD cell-adhesive sequence from fibronectin (FN) represents a promising approach in regenerative medicine. However, these biomimetic strategies have yielded only marginal enhancements in tissue healing in vivo. In this study, clinical-grade titanium implants were grafted with a non-fouling oligo(ethylene glycol)-substituted polymer coating functionalized with controlled densities of ligands of varying specificity for target integrin receptors. Biomaterials presenting the alpha5beta1-integrin-specific FN fragment FNIII 7-10 enhanced osteoblastic differentiation in bone marrow stromal cells compared to unmodified titanium and RGD-presenting surfaces. Importantly, FNIII 7-10-functionalized titanium significantly improved functional implant osseointegration compared to RGD-functionalized and unmodified titanium in vivo. This study demonstrates that bioactive coatings that promote integrin binding specificity regulate marrow-derived progenitor osteoblastic differentiation and enhance healing responses and functional integration of biomedical implants. This work identifies an innovative strategy for the rational design of biomaterials for regenerative medicine.     

In vivo molecular evidence of delayed titanium implant osseointegration in compromised bone

Optimization of implant osseointegration in patients with reduced bone healing potential is a challenge remaining in implant dentistry. Identification of the genes that are modulated during implant osseointegration in normal versus osteopenic bone is needed to successfully address these pertinent clinical needs. The present study aimed to assess the initial and early molecular events following titanium implant installation in normal and compromised bone in a rat tibia model. Peri-implant tissue from a well-defined tissue regeneration compartment was analyzed at 2 and 7 days post-surgery for the expression of select markers of inflammation, angiogenesis, bone resorption and bone formation. Impaired bone was induced by hindlimb unloading and validated using μCT. The essential step of angiogenesis preceding bone regeneration was evidenced for the peri-implant setting in healthy bone. Compromised bone significantly affected the angiogenesis-osteogenesis coupling in the initial phase (2?days post-surgery), with altered expressions of Vegfa and Epas1 coinciding with downregulated expressions of Col1a1, Bmp2, Bmp4, Alpl and Bglap. At 7 days post-implantation, differences between normal and compromised peri-implant bone were no longer observed. This in vivo molecular evidence of delayed implant osseointegration in compromised bone reassert modern strategies in implant development, such as surface modifications and bioengineered approaches, to improve implant osseointegration in compromised conditions.     

质子泵抑制剂FR167356对骨质疏松模型兔种植体骨整合的影响

背景：破骨细胞质膜上的空泡型质子泵是骨组织溶解必不可少的关键酶,空泡型质子泵抑制剂对体外培养的破骨细胞有明显的抑制作用。 目的：观察质子泵抑制剂FR167356对骨质疏松家兔种植体周围骨整合的影响。 方法：将24只5月龄雌性家兔随机分成单纯卵巢切除组、质子泵抑制剂组及假手术组,每组8只,前2组家兔切除双侧卵巢,假手术组只切除卵巢周围等量的脂肪组织。卵巢摘除12周后,在所有家兔的双侧胫骨近心端各置入1枚纯钛种植体(长8 mm,直径3.3 mm)。质子泵抑制剂组在种植体周围肌注FR167356,其他2组肌注等量的生理盐水。在种植后4,12周进行X射线片、组织形态学观察及拔出力学实验。 结果与结论：X射线片检查结果显示种植后第4周时,单纯卵巢切除组种植体的高阻射影像、种植体螺纹间隙的低密度影像、骨组织的界限明显比其他2组清楚;12周时,与单纯卵巢切除组相比,假手术组和质子泵抑制剂组种植体螺纹间隙的密度与周围骨组织更接近,种植体与周围骨组织的界限消失的更明显,2组无明显差异。组织学观察结果发现,4周时假手术组和质子泵抑制剂组种植体周围骨质多孔,平行于种植体表面的骨小梁排列紧密,小梁间连接较多,2组无明显差异;12周时假手术组和质子泵抑制剂组种植体周围骨组织量比4周时明显增加,骨小梁增粗且粗细均匀,连接紧密且间隙减小,单纯卵巢切除组没有观察到这种现象。在力学实验中,第4,12周,单纯卵巢切除组的最大拔出力值明显低于其他2组。提示局部应用质子泵抑制剂FR167356对骨质疏松家兔种植体骨整合有显著的促进作用。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

No deleterious effect of low dose methotrexate on titanium implant osseointegration in a rabbit model

OBJECTIVE:

To evaluate the effect of low dose methotrexate alone or in combination with glucocorticoid treatment on titanium implant osseointegration.

METHODS:

Groups of 6–8 adult New Zealand White rabbits were treated for 18 weeks with saline (control), methotrexate, glucocorticoid, or methotrexate plus glucocorticoid. The animals received a titanium implant in the tibia at week 6. Lumbar spine and tibia bone mineral densities were analyzed before and after treatment. Histomorphometric analysis of bone cortical thickness, total bone area around the implant, and % of bone to implant contact was performed.

RESULTS:

After 18 weeks, the change in the bone mineral density in the lumbar spines and tibias in the methotrexate group was comparable to the control group (0.035 vs. 0.055 g/cm² and 0.021 vs. 0.041 g/cm², respectively). In contrast, both the glucocorticoid group and glucocorticoid plus methotrexate group had significant reductions at both sites. Histomorphometric analysis of the tibia in the control and methotrexate groups revealed no significant changes in cortical thickness (133 vs. 126 µm), total bone area around the implant (33 vs. 30%), or bone to implant contact (40 vs. 38%). In contrast, glucocorticoid group had significant reductions compared to controls in tibia cortical thickness (99 vs. 133 µm), total bone area around the implant (24 vs. 33%), and bone to implant contact (27 vs. 40%). Similar reductions were observed in the glucocorticoid plus methotrexate group.

CONCLUSIONS:

Our results demonstrate that low dose methotrexate treatment does not affect titanium implant osseointegration, suggesting that this therapy is safe for surgical procedures requiring a titanium implant.