聚醚醚酮表面多孔羟基化改性对MC3T3-E1细胞黏附、增殖的影响

目的对聚醚醚酮(polyetheretherketone,PEEK)薄片表面进行多孔化和羟基化改性,观察PEEK表面形貌和生物活性的变化,并探讨该改性方法对前成骨MC3T3-E1细胞黏附、增殖的影响。方法超声波环境下浓硫酸处理PEEK表面,在其表面形成大量微孔结构;经湿化学法将PEEK表面的酮类基团还原成羟基基团,改善其表面化学活性,提升PEEK薄片的生物相容性。利用扫描电子显微镜(SEM)、傅里叶变换红外光谱仪(FTIR)及静态水接触角检测改性前后材料表面形貌、化学基团及亲水性的变化。未处理PEEK、多孔化PEEK、羟基化PEEK、多孔羟基化PEEK与MC3T3-E1细胞共培养,评价表面改性后PEEK薄片对细胞黏附、增殖的影响。结果 SEM结果显示浓硫酸处理后的PEEK薄片表面形成密集的空隙大小均匀的微孔结构,FT-IR结果证实羟基化改性成功地在PEEK表面还原出了大量羟基基团。同时,表面多孔化和羟基化改性均可有效提升PEEK材料表面的亲水性能。在体外细胞实验中,不同改性的PEEK材料与MC3T3-E1细胞共培养后结果显示,多孔化、羟基化和多孔羟基化改性均可显著促进细胞黏附和伸展,同时随着时间的延长,其促进细胞增殖的功能也逐步增强。结论表面多孔羟基化改性能有效提高PEEK材料表面的生物学活性和亲水性能,进而显著促进细胞的黏附和增殖。     

聚醚醚酮/58S生物活性玻璃骨植入材料的成骨活性

目的探讨聚醚醚酮/58S生物活性玻璃(PEEK/58S)骨植入材料的成骨活性。方法 MG-63成骨细胞在PEEK和PEEK/58S表面培养一段时间后,扫描电镜(SEM)观察MG-63成骨细胞的黏附铺展状态;CCK-8法检测MG-63成骨细胞的增殖活性;碱性磷酸酶(ALP)活性检测评价MG-63成骨细胞的成骨分化能力;实时荧光定量PCR(RT-qPCR)检测成骨分化相关基因ALP、BMP-2、COL-I、OCN、OPN mRNA表达。PEEK和PEEK/58S植入大鼠胫骨近端12周后,组织学染色和生物力学拔出实验评价骨植入材料与周围骨组织之间的骨整合能力。结果与纯PEEK相比,PEEK/58S更有利于MG-63成骨细胞的黏附铺展,能显著改善MG-63成骨细胞的增殖活性和ALP活性(P0.05),显著促进ALP、BMP-2、COL-I、OCN、OPN mRNA的表达(P0.05)。PEEK/58S比纯PEEK表现出更好的骨整合能力。结论 PEEK/58S骨植入材料能显著改善成骨细胞的黏附、铺展、增殖与成骨分化活性,增强其与周围骨组织之间的骨整合能力,有望作为新型骨植入材料用于临床。     

光固定明胶修饰的聚醚醚酮(PEEK)表面促进细胞增殖及成骨性研究

目的聚醚醚酮(PEEK)具有与骨骼相似的弹性模量,但PEEK作为骨修复材料的应用受到其表面生物惰性及缺乏促成骨性的限制。为了解决这个问题,我们通过表面修饰光固定明胶增强PEEK生物活性。方法我科研团队合成的光固定明胶可通过紫外照射粘附于多种材料表面,并可增强材料的生物相容性。进行SEM、静态水接触角、细胞增殖、细胞形态、碱性磷酸酶分化等表征学及细胞学系统研究。结果研究表明光固定明胶可固定于PEEK表面,改变了PEEK等高分子材料的表面性质。在细胞学研究中,光固定明胶改性后相对于普通PEEK,成骨细胞增殖、伸展、基质分泌及分化能力明显增强。结论通过光固定明胶对PEEK表面进行改性,可明显增强其生物活性,是一种有潜力的骨科内植入物及医疗器械材料。     

医用聚醚醚酮材料骨整合改性的研究进展

聚醚醚酮（PEEK）材料具有良好的生物相容性、优异的机械性能、与骨组织相似的力学性能等优点,目前已广泛应用于临床各个领域。由于固有的生物惰性,使种植体与骨组织不相整合,从而限制了其作为骨科植入材料的应用。提高PEEK骨整合性成为目前研究的热点。研究者将具有促进成骨细胞增殖和分化的材料（如生物陶瓷、金属材料、生物因子等）通过物理或化学方式修饰于材料表面,或者采用表面物理修饰（如粗糙度、孔隙率、纳米结构等）提高其骨整合性。随着研究的逐步深入,PEEK的成骨活性得到增强,在临床上有了更大的应用前景。本文主要对上述提到的近些年用于提高PEEK生物活性的方法作一综述,旨在为研究者提供参考,并对未来发展提出展望。     

医用钛合金材料表面改性对骨整合影响的研究进展

医用钛合金材料是临床应用中较为常见的骨科植入物材料之一,作为一种具备良好的生物相容性、耐腐蚀性以及机械强度的生物材料受到了学者的广泛关注。本文专注于PubMed和Web of Science数据库中的相关文献,着重论述4种不同的表面改性设计对医用钛合金材料骨整合性能的影响。在材料学结构设计不断创新和深入研究的背景下,针对医用钛合金材料表面改性设计对骨整合影响的研究发展现状进行综述。     

聚醚醚酮各向异性 3D 打印对股骨替代物力学性能的影响

目的 针对材料挤出成形3D打印聚醚醚酮(polyetheretherketone, PEEK)骨替代物制造工艺存在明显各向异性的问题,以下肢股骨为例,研究不同摆放方式下3D打印PEEK股骨替代物的力学性能。方法 在有限元模型中模拟人体步态周期中5种姿态,改变正交各向异性,计算不同打印摆放方式下股骨应力与变形,并通过力学实验研究3D打印PEEK股骨的安全性与稳定性。结果 竖直摆放优于水平摆放方式,此时3D打印PEEK股骨替代物最大应力为46.56 MPa,低于PEEK材料的屈服强度但变形量大于自然股骨,满足服役过程中力学性能需求,而承载稳定性有待提高。结论 使用材料挤出成形制造承重骨时应优先采用竖直摆放的方式,3D打印技术在用于承重部位骨替代物时应谨慎考虑其各向异性对替代物服役性能的影响。     

多孔钽的理化/生物特性及其骨整合能力研究进展

近年来,以钛合金为主的骨骼材料得到了广泛的应用。临床研究中,植入体的腐蚀磨损和骨整合能力不足是造成其无菌性松动的主要原因,最终可导致手术失败。因此制备综合性能优越的植入体材料是骨组织工程研究的热点。多孔钽拥有良好的理化性质,耐腐蚀和抗磨损性能出色,其良好的生物相容性和多孔结构可以促进新骨的长入和成骨细胞的增殖,从而提高骨整合能力。并且表面改性技术的发展赋予了多孔钽更加优良的性能和功能,扩展了其临床应用。本文将针对多孔钽的理化/生物特性及其骨整合能力的研究进展进行综述。     

钙磷涂层中掺入锌对成骨的影响及其潜在生物学机制

种植体表面涂层改性可提高其骨诱导性,其中单纯钙磷涂层已被广泛研究,但其促骨整合速率慢、抗菌性低,其他金属离子如纳米锌离子的加入可弥补这些缺陷。本文阐述了该改良涂层中纳米锌的掺入形式、对材料理化性能的影响以及抑菌性,同时归纳了钙离子、锌离子和无机磷赋予材料的生物学性能主要集中于三种无机离子对成骨细胞增殖分化、蛋白合成及基质矿化等方面的作用,以全面阐述纳米掺锌钙磷涂层对骨形成的促进作用。     

碳纤维增强聚醚醚酮复合材料生物摩擦学研究进展

碳纤维增强聚醚醚酮(CF/PEEK)复合材料具有优异的生物相容性、生物力学及生物摩擦学性能,有望成为人工关节替换材料。本文阐述了润滑介质、增强体的表面改性、功能性粒子填充、摩擦副材料及摩擦运动方式等因素对CF/PEEK复合材料生物摩擦磨损性能的影响,指出今后应加强对多因素协同作用下CF/PEEK复合材料磨损机制与润滑机制的研究。     

β-TCP材料改性研究进展及在骨缺损修复中的应用*

大段骨缺损再生修复是临床骨科面临的难题之一,利用组织工程材料修复大段骨缺损是最具前景的治疗方式。β-TCP材料由于具有与自体骨相似的无机成分,良好的生物相容性、可吸收降解以及骨传导等性能被广泛应用于骨科临床治疗。虽然β-TCP材料是一种最具潜力的骨替代材料,但是还存在诸如降解速率与新骨再生速率不匹配、脆性大力学强度不够、骨诱导能力差等缺陷,从而阻碍其临床应用。采用其他材料对β-TCP材料改性提高降解、力学及骨诱导等性能是目前研究热点。本文就β-TCP材料改性研究及在骨缺损再生修复中的应用作一综述。     

Effect of micro-roughening of poly(ether ether ketone) on bone marrow derived stem cell and macrophage responses,and osseointegration

Poly(ether ether ketone) (PEEK) has emerged as a candidate to replace metal implants because of its satisfactory mechanical properties, radiolucency, and lack of metal allergy. However, PEEK lacks osseointegration ability limiting its clinical applications. To overcome this problem, we prepared PEEK with a micro-rough surface using the sandblast method to modulate its osseointegration property; the sandblast method is simple, cost-effective, and is already applied to clinical metal implants. The surface roughness of the sandblasted PEEK was about 2.3 μm, whereas that of mirror-polished PEEK was 0.06 μm. Rat bone marrow-derived mesenchymal stem cells (RMSCs) showed higher proliferation, osteocalcin (OC) expression and bone-like nodule formation on micro-roughened PEEK compared with those cultured on mirror-polished PEEK, suggesting that micro-roughening facilitated RMSCs proliferation and differentiation. The micro-roughened surface slightly mitigated secretion of inflammatory C-C motif chemokine 2 (CCL-2) from lipopolysaccharide (LPS)-stimulated macrophages, but not of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). Finally, to compare osseointegration, specimens were implanted in rat femur bone marrow cavities, and then the pull-out force was measured. The pull-out force of micro-roughened PEEK was about four times higher than that of the mirror-polished PEEK. These results showed that micro-roughening of PEEK using the sandblast method was able to improve osseointegration, partly through elevating proliferation and differentiation of RMSCs.     

Enhanced antibacterial property and osteo-differentiation activity on plasma treated porous polyetheretherketone with hierarchical micro/nano-topography

Implantable polyetheretherketone (PEEK) has great biomedical potential as hard tissue substitute in orthopedic application due to its outstanding mechanical properties and excellent biological stability. However, the poor osseointegration and bacteriostatic ability of implantable PEEK become the major barrier for its wide clinic application. In this study, a hierarchically micro/nano-topographic PEEK with specific functional groups (amino and COOH/COOR) has been fabricated using facile sulfonation combined with argon plasma treatment. The new developed hierarchically micro/nano-topographic PEEK have enhanced hydrophilicity, surface roughness, as well as the high ability of apatite-layer forming. Antibacterial assessment shows that as-treated samples exhibit better antibacterial activity. The cellular responses in osteoblast-like MG-63 cells culturing experiment reveal that the micro/nano-topography accompanied with specific functional groups improves the cell adhesion at the initial stage, further ameliorates proliferation and osteogenic differentiation of MG-63. This study proposes a promising approach to increase osteo-differentiation activity and bacteriostasis of PEEK via synergistic effects involving surface topologic structure and chemical modification, which shows great potential in developing advanced implantable materials.     

Osseointegration of machined,injection moulded and oxygen plasma modified PEEK implants in a sheep model

Machined and injection moulded polyetheretherketone (PEEK) implants with and without an oxygen plasma modification were prepared and implanted in sheep cancellous and cortical bone. After 4, 12 and 26 weeks, osseointegration was evaluated through mechanical push-out tests and histomorphometry. In the cancellous bone, push-out force increased with time, a trend toward higher force was observed for machined compared to moulded, and oxygen plasma modified compared to unmodified. On-going remodelling of the bone was detected in the periphery of the implants at 4 weeks. Minimal or no inflammation was observed with all the implants at all locations and time-points. Bone-implant contact (BIC) was quantified at all-time points and locations for all the four PEEK implant surfaces. The BIC values ranged from 15 to 75% with an average of 29 ± 13% in the cancellous bone and 25–65% with an average of 50 ± 12% in the cortical bone. In the cortical bone the BIC increased significantly from 4 to 26 weeks. This in vivo study has identified that surface topography of PEEK implants influences osseointegration. In addition, oxygen plasma has the potential to increase bone-implant interface stability. This study provides a unique reference for further modifications and in vivo assessment of PEEK implants.     

Polyetheretherketone/nano-fluorohydroxyapatite composite with antimicrobial activity and osseointegration properties

Lack of antibacterial activity and binding ability to natural bone tissue has significantly limited polyetheretherketone (PEEK) for many challenging dental implant applications. Here, we have developed a polyetheretherketone/nano-fluorohydroxyapatite (PEEK/nano-FHA) biocomposite with enhanced antibacterial activity and osseointegration through blending method. Smooth and rough surfaces of PEEK/nano-FHA biocomposites were also prepared. Our results showed that in vitro initial cell adhesion and proliferation on the nano-FHA reinforced PEEK composite were improved. In addition, higher alkaline phosphatase activity and cell mineralization were also detected in cells cultured on PEEK/nano-FHA biocomposites, especially for rough PEEK/nano-FHA surfaces. More importantly, the as-prepared PEEK/nano-FHA biocomposite could effectively prevent the proliferation and biofilm formation of bacterial. For in vivo test, the newly formed bone volume of PEEK/nano-FHA group was higher than that of bare PEEK group based on 3D microcomputed tomography and 2D histomorphometric analysis. These reports demonstrate that the developed PEEK/nano-FHA biocomposite has increased biocompatibility and antibacterial activity in vitro, and promoted osseointegration in vivo, which suggests that it holds potential to be applied as dental implant material in dental tissue engineering applications.     

钛种植体表面改性策略及对骨整合的影响

背景：纯钛因具有优良的生物相容性、机械性能和与骨组织相近的弹性模量等被广泛应用于口腔种植领域。 目的：综述近年来钛金属种植体材料表面物理改性、化学改性和生物化学改性策略的研究进展。 方法：以“titanium,implant,surface modification,osseointegration”为检索词,检索PubMed数据库,以“钛,种植体,表面改性,骨整合”为检索词,检索中国知网数据库,限定时间范围为2007年1月至2013年2月。文献检索语种为英文和中文。纳入内容与钛种植体表面改性方法及其对骨整合影响密切相关的文献,排除重复文献。 结果与结论：计算机初检得到199篇文献,根据纳入排除标准,对其中76篇文献进行分析。钛种植体本身是生物惰性材料,通过表面改性对钛金属表面进行活化处理,使之具有生物功能性,与骨组织形成早期骨整合,是国内外口腔种植材料研究的热点问题。物理改性、化学改性和生物化学改性可缩短钛种植体种植周期,获得早期骨整合和更高的结合强度。今后的发展趋势是将多种改性方法有机结合,从分子水平深入研究钛金属材料表面与机体细胞和组织之间的界面分子作用机制,完善种植体的表面改性技术,实现种植体和骨组织的早期和更加稳定的骨整合。     

Cytocompatibility,osseointegration, and bioactivity of three-dimensional porous and nanostructured network on polyetheretherketone

Porous biomaterials with the proper three-dimensional (3D) surface network can enhance biological functionalities especially in tissue engineering, but it has been difficult to accomplish this on an important biopolymer, polyetheretherketone (PEEK), due to its inherent chemical inertness. In this study, a 3D porous and nanostructured network with bio-functional groups is produced on PEEK by sulfonation and subsequent water immersion. Two kinds of sulfonation-treated PEEK (SPEEK) samples, SPEEK-W (water immersion and rinsing after sulfonation) and SPEEK-WA (SPEEK-W with further acetone rinsing) are prepared. The surface characteristics, in vitro cellular behavior, in vivo osseointegration, and apatite-forming ability are systematically investigated by X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, cell adhesion and cell proliferation assay, real-time RT-PCR analysis, micro-CT evaluation, push-out tests, and immersion tests. SPEEK-WA induces pre-osteoblast functions including initial cell adhesion, proliferation, and osteogenic differentiation in vitro as well as substantially enhanced osseointegration and bone-implant bonding strength in vivo and apatite-forming ability. Although SPEEK-W has a similar surface morphology and chemical composition as SPEEK-WA, its cytocompatibility is inferior due to residual sulfuric acid. Our results reveal that the pre-osteoblast functions, bone growth, and apatite formation on the SPEEK surfaces are affected by many factors, including positive effects introduced by the 3D porous structure and SO₃H groups as well as negative ones due to the low pH environment. Surface functionalization broadens the use of PEEK in orthopedic implants.     

颅骨修补材料研究现状及3D打印技术应用前景

BACKGROUND: Skull repair materials cannot only restore the normal shape of the skull, but also play an important role in brain functional recovery. OBJECTIVE: To summarize the research status of polyetheretherketone (PEEK), titanium alloy and tissue engineering technique in cranioplasty and the prospect of three-dimensional (3D) printing technology. METHODS: Literatures related to skull repair materials were retrieved in databases of CNKI and PubMed published from 1995 to 2016, using the keywords of “bone regeneration material in calvarial, 3d printing bone scaffold” in Chinese and English, respectively.  RESULTS AND CONCLUSION: Although titanium and PEEK have been used in clinic, titanium holds conductivity, thermal conductivity, while PEEK that may be displaced or lost is not involved in osseointegration. Tissue engineering technology participates in the skull tissue reconstruction, achieving satisfactory repair outcomes, but the problems of scaffold selection and preparation, seed cell obtainment, and growth factor release need to be overcomed. 3D printing technology can print personalized shape, fit the defect precisely, but the raw materials should have good biocompatibility and biomechanical property. Combination of tissue engineering technology with 3D printing technology shows a broad prospect in cranioplasty.     

MRI and dental implantology: Two which do not exclude each other

Currently, histological techniques are used to analyse implant-tissue-interactions. However, these methods are destructive and time-consuming. Furthermore, they require a large number of animals as longitudinal observations in one individual are not possible. The evaluation by non-destructive imaging techniques provides the opportunity to study the osseous integration with a reduced number of animals and a decreased biological variability.The present study examined the suitability of magnetic resonance imaging (MRI) to assess peri-implant bone formation exemplarily for a dental implant in a minipig model. Due to its compatibility to MR imaging polyetheretherketone (PEEK) coated with a thin layer of titanium was applied as implant material. Osseointegration was analysed within different peri-implant regions quantifying bone volume density and soft tissue content, which were assessed by MRI and histology, likewise.It could be proven that the examined regions showed differences in bone formation; the region adjacent to the implant apex turned out to be the most dynamic. Both methods led to comparable results with no significant differences regarding to the assessed parameters.Moreover, it was demonstrated that titanium coated PEEK showed a sufficient osseointegration and MRI provides a promising application in monitoring bone formation.