骨组织工程基质材料的现状及展望

通过阐述理想骨组织工程细胞外基质材料的要求,并总结生物类材料、生物陶瓷类材料、聚合物类材料和复合类材料在骨组织工程中用作细胞外基质材料的优缺点,认为理想的骨组织工程细胞外基质材料最好由生物陶瓷类材料、人工合成聚合物类材料或天然聚合物类材料组成,并含有最佳的生长因子缓释系统的多孔三维立体泡沫,这种复合型细胞外基质材料的研制是骨组织工程研究中十分重要而迫切的任务。     

注射型rhBMP-2/PLGA/FS缓释微球载体系统用于兔桡骨骨缺损修复的实验研究

探讨注射型重组人骨形态发生蛋白-2/聚乳酸-羟基乙酸/纤维蛋白胶(rhBMP-2/PLGA/FS)缓释微球载体系统在修复兔桡骨节段性骨缺损中的作用。制作新西兰大白兔桡骨缺损模型,将其分为实验组(rhBMP-2/PLGA/FS),对照组(FS)和空白组(不作处理)。在缺损局部注入各组材料后,通过X射线观察各组动物的骨缺损修复情况;取兔桡骨损伤节段定量分析其骨密度值,评估其成骨质量;利用HE及Masson染色,观察骨组织形态及骨再生情况,评估其修复作用。结果表明:rhBMP-2/PLGA/FS缓释微球载体组在骨缺损修复、成骨质量及成骨能力方面均显著优于对照组和空白组,能够显著促进兔骨缺损修复,是一种较为理想、高效的骨组织工程材料。     

PLGA仿生矿化对骨髓基质干细胞黏附率的影响

目的研究仿生矿化的聚乳酸-羟基乙酸共聚物(PLGA)作为骨组织工程支架材料的可行性。方法将三维多孔PLGA材料在模拟体液中矿化2周,检测材料表面矿化物的形貌及成分。采用优化的梯度离心法获取大鼠骨髓基质干细胞(BMSCs),经传代培养后作为种子细胞与PLGA材料于体外联合培养,同时以未矿化的PLGA材料和煅烧松质骨为对比,初步观察仿生矿化的PLGA支架材料与BMSCs复合培养的情况,计算各材料细胞黏附率。结果矿化后的PLGA材料网孔壁有磷灰石矿化层形成。骨髓基质干细胞和支架材料体外复合培养24h,矿化的PLGA细胞黏附率明显高于未矿化的PLGA(α<0.05),和煅烧松质骨没有明显的差别(α>0.05)。结论仿生矿化可以改善PLGA早期细胞黏附性能,是构建骨组织工程支架材料的较好方法。     

骨组织工程植入物的表面修饰

文题释义：骨组织工程：是应用生物学和工程学的原理,研究开发能够修复、维持和改善骨组织功能的生物替代物的一门研究。替代物包括自体组织、同种异体组织、异种组织和人工合成物质。 表面修饰：通过无机成分、有机成分或改变植入物表面地貌的方法来对骨科植入材料进行表面的生物修饰,从而改善骨植入物的生物性能。 背景：骨组织工程植入物已被广泛应用于骨科治疗,但现有的骨植入物往往还存在着力学性能差、免疫反应、微生物感染、愈合不良等缺点,不同的表面修饰技术可以有效弥补这些不足。 目的：对现有骨组织工程植入物的表面修饰技术做一综述。 方法：由第一作者检索 2000至2019年 PubMed数据库、中国知网、维普中国期刊网等收录的与骨组织工程表面修饰相关的文献,优先选择近期发表或发表在权威杂志上的文章。英文检索词为“bone tissue engineering;bone implant;surface modification;coating”,中文检索词为“骨组织工程;骨植入物;表面改性;涂层”。 结果与结论：通过无机成分、有机成分或改变植入物表面地貌的方法来对骨组织工程植入材料进行表面生物修饰,不同程度地改善了骨植入物的成骨性、骨传导性、抑菌性、生物相容性等。但是要将这种新植入体应用与临床,还需要解决一下问题：如何确定不同表面修饰成分的最佳浓度,最大限度地促进骨愈合和抑制细菌活性,且避免其他不良反应;如何避免随着时间的推移,这些骨组织工程植入物发生表面磨损而产生的颗粒导致的异物反应和免疫反应;如何将各种生长因子、蛋白质、和其他生物分子纳入涂层,而不损害其各自的化学结构和功能;如何以协同和可控的方式引导生长因子和分子的释放。 ORCID: 0000-0001-7045-7776(方旭) 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     

血管内皮生长因子缓释系统复合成骨诱导的骨髓间质干细胞修复骨缺损

背景：从目前文献报道来看,生长因子缓释系统在骨科方面的应用研究主要集中在软骨修复方面,关于复合组织工程骨修复骨缺损的研究报道较少。 目的：构建复合组织工程骨,观察其修复骨缺损的效果。 方法：①通过血管内皮生长因子、肝素和纤维蛋白胶的不同组合构建复合支架缓释系统,经检测选取最优组种植成骨诱导的骨髓间质干细胞构建复合组织工程骨。②36只SD大鼠制备股骨干骨缺损模型后随机分为3组,分别植入上述复合组织工程骨和复合支架缓释系统,空白对照组不植入任何材料,3组均予内固定。③ELISA方法检测样本释放的血管内皮生长因子浓度以评价复合支架缓释系统的缓释性能;于植入后1,4,12,24周行X射线检查及骨组织碱性磷酸酶染色评价各组动物骨缺损修复水平。 结果与结论：经血管内皮生长因子/肝素/纤维蛋白修饰的纳米晶胶原基骨复合支架缓释系统在体外环境缓释30 d后依然高浓度释放血管内皮生长因子,且缓释曲线平直;动物实验中植入的复合组织工程骨在24周内完全降解,骨缺损修复完成,骨缺损部位碱性磷酸酶活性明显高于复合支架缓释系统组、空白对照组。结果显示该复合支架缓释系统具有优异的缓释性能,在该缓释系统上种植成骨诱导的骨髓间充质干细胞后,能够提高骨缺损修复的速度和质量。     

利福平/聚乳酸-聚羟基乙酸缓释微球的制备及特性

背景：虽然国内外有很多制备利福平/聚乳酸-聚羟基乙酸共聚物(poly lactic acid-glycolic acid copolymer,PLGA)微球的报道,但这些微球粒径多在10 μm左右,不适合与磷酸钙骨水泥复合制备成具有良好降解性的抗结核修复材料。 目的：制备大粒径利福平/PLGA缓释微球,观察其理化特性和体外缓释特性。 方法：以PLGA为载体,将利福平分散于PLGA的有机溶剂中,采用复乳溶剂挥发法制备利福平/ PLGA缓释微球。光镜和扫描电镜下观察微球的形态特征,测定微球平均直径和跨距,高效液相色谱法测定载药量和包封率,以溶出法和高效液相色谱法观察其体外释药特性,并拟合药物体外释放曲线建立曲线方程。 结果与结论：利福平/PLGA微球电镜观察呈圆球形,分散性好,粘连少,粒径分布集中,平均粒径(80.0±9.4) μm。载药量、包封率分别为(33.18±1.36)%,(54.79±1.13)%。体外缓释试验显示突释期内微球释放度为(14.66±0.18)%,前3 d累计释放度(18.09±0.45)%,到42 d体外累积释放度达到(92.17±1.23)%。提示利福平/PLGA微球具有良好的缓释效果,是一种较为理想的抗结核药物的载体材料和释放系统;PLGA是良好的药物缓释载体,可以用来制备载药缓释微球。     

生长因子缓释制剂在神经系统退变性疾病中的应用

利用缓释系统包载生长因子,既能保护生长因子的生物活性,又可以使其缓慢释放。从载体材料与生长因子的简单混合到生长因子缓释微球系统,生长因子缓释技术不断更新并得到广泛应用。就生物可降解生长因子缓释制剂在神经系统退变性疾病中的应用做一综述。     

血管内皮生长因子/纳米晶胶原基骨缓释系统与人骨髓间充质干细胞的体外生物相容性

背景:利用载体或缓释系统负载生长因子,既能保护生长因子的生物活性,又可以使生长因子缓慢释放,从而持续促进细胞生长及组织修复再生,是目前控制释放载体材料应用研究的方向之一。目的:观察血管内皮生长因子/纳米晶胶原基骨缓释系统的体外缓释效果及与种子细胞的生物相容性。方法:人骨髓间充质干细胞经体外诱导培养、扩增后种植于血管内皮生长因子+肝素/纤维连接蛋白+纳米晶胶原基骨支架(实验组)和单纯的纳米晶胶原基骨支架(对照组)行体外培养。测定缓释支架材料上血管内皮生长因子的释放量和持续时间;种植细胞后细胞的黏附率;培养3,7,10,14d时支架材料中细胞数、碱性磷酸酶活性以及细胞在材料上的生长状况。结果与结论:①该缓释支架具有一定的血管内皮生长因子缓释效果,持续时间可达14d。②第3代人骨髓间充质干细胞经成骨诱导培养,可表达成骨细胞表型:碱性磷酸酶细胞化学染色、I型胶原免疫荧光染色均为阳性。③体外实验显示该缓释支架与人骨髓间充质干细胞具有优良的生物相容性:相同时间点实验组的细胞黏附率、支架上细胞数量及细胞碱性磷酸酶活性均明显高于对照组;扫描电镜发现两组材料上均有细胞生长,但实验组的细胞生长状况明显好于对照组。     

纳米晶胶原基骨/血管内皮生长因子缓释支架对人骨髓间充质干细胞体外粘附增殖的影响

研制纳米晶胶原基骨(nHAC)/血管内皮生长因子(VEGF)缓释支架,了解VEGF体外缓释效果及对人骨髓间充质干细胞(human mesenchymal stem cells,hMSCs)成骨诱导后粘附、增殖的影响,为骨组织工程寻求一种新型复合支架材料.利用生物学方法将VEGF负载于nHAC,制备具有VEGF缓释效果的复合支架;hMSCs经体外培养、扩增、成骨诱导后种植于VEGF缓释支架上行体外增殖.分为四组:实验组A:nHAC、纤维连接蛋白(fibronectin,FN)、肝索(heparin,HP)和VEGF(nHAC-FN-HP-VEGF);对照组B:nHAC、FN和VEGF(nHAC-FN-VEGF);对照组C,nHAC、HP和VEGF(nHAC-HP-VEGF);对照组D:nHAC和VEGF(nHAC-VEGF).通过检测支架材料上VEGF的释放量和持续时间,及种植细胞后细胞的黏附率、不同时间点(3、7、10、14 d)支架材料中细胞数、碱性磷酸酶活性以及扫描电镜观察细胞在材料上的生长状况,比较分析不同复合支架材料对细胞粘附、增殖的影响.人第三代MSCs 经诱导培养14 d后,碱性磷酸酶细胞化学染色、Ⅰ型胶原免疫荧光染色均为阳性;实验组A的VEGF缓释量最高,持续时间最长(可达14 d),细胞黏附率最高,为61.8%;各组支架中的细胞数量均随培养时间延长而增长,实验组A的细胞数增加较快,与相同时间点其他各组材料中细胞数差异有显著性(P<0.05);各时间点细胞碱性磷酸酶活性表达实验组最高,差异亦有显著性(P<0.05).电镜打描发现4组材料上均有细胞生长,实验组A的细胞增殖、分化状况明显好于其他组.hMSCs经诱导培养后可具有成骨细胞特性,hHAC-FN-HP-VEGF缓释支架具有较好的VEGF缓释效果,能显著提高细胞的粘附和增殖,可作为较理想的新型复合支架应用于骨组织工程.     

可注射型组织工程骨支架材料的研究进展

可注射型组织工程骨支架材料是一种具有一定形态和机械强度的支架材料,可与种子细胞复合,以流体的形式注射到骨组织缺损部位,最终形成新骨,达到结构恢复和功能重建的目的.此材料具有创伤小、可塑性好的特点,可以修复形态不规则的骨缺损,能够很好地复合生长因子,是目前较为理想的骨组织缺损的修复方式.在众多可注射骨组织工程材料中,生物陶瓷材料、高分子材料等被证明有高度的生物相容性和良好的机械性能,已成为骨组织工程材料方面的研究重点.旨在对生物陶瓷材料、高分子材料、生物陶瓷与高分子复合材料的发展与应用作一综述.     

可降解生物材料聚乳酸-羟基乙酸仿生矿化的实验研究

目的：通过对聚乳酸-羟基乙酸共聚物(poly lactide-co-glycolide，PLGA)的仿生矿化，表面改性，以提高其细胞粘附性；探讨影响仿生矿化的因素和条件，为进一步制备组织工程化人工骨提供依据和实验基础。方法：PLGA膜经碱性溶液水解处理后，应用高温显微镜测量材料表面润湿角的变化；碱处理后的PLGA膜和三维多孔PLGA分别在模拟体液(Simulated Body Fluid，SBF)中矿化14d，在1．5倍SBF中矿化9d，应用扫描电镜进行矿化物形貌观察，X射线能谱分析钙磷比值，X射线衍射仪和傅立叶转换红外光谱仪行矿化物物相分析。结果：PLGA经碱性溶液水解处理后表面亲水性明显增强，在SBF及1．5倍SBF中矿化后表面可以形成明显的矿化物；矿化物的形态与矿化液的浓度有关；矿化物主要成分为羟基磷灰石(HA)，含有碳酸根成分，钙磷比为1．53，类似于人骨无机质。结论：PLGA仿生矿化是制备结构及性质类似骨基质人工骨的可行方法。     

Increased osteoblast functions among nanophase titania/poly(lactide-co-glycolide) composites of the highest nanometer surface roughness

Currently, the scientific challenges for bone tissue engineering lie in the development of suitable scaffold materials that can improve bone cell adhesion, proliferation, and differentiation. The design of nanophase titania/poly(lactide-co-glycolide) (PLGA) composites offers an exciting approach to combine the advantages of a degradable polymer with nanosize ceramic particles to optimize the physical and biological properties necessary for bone regeneration. Moreover, because of the presence of nanosized ceramics, such composites can be formulated to match the surface roughness of bone. For these reasons, the objective of the present in vitro study was to investigate osteoblast (bone-forming cell) adhesion and long-term functions on nanophase titania/PLGA composites that mimic the surface roughness of bone. Various sonication powers were applied in this study to manipulate titania dispersions in PLGA and consequently control their surface roughness. Most importantly, results correlated better osteoblast adhesion and long-term functions (such as collagen, alkaline phosphatase activity, and calcium-containing mineral deposition) among nanophase titania/PLGA composites that had surface roughness values closer to natural bone. In this manner, this present study demonstrated that the nanophase titania/PLGA composites sonicated to have nanometer surface roughness values can improve osteoblast functions necessary for enhanced bone tissue engineering applications.     

Porous poly(DL-lactic-co-glycolic acid)/calcium phosphate cement composite for reconstruction of bone defects

Calcium phosphate (Ca-P) cements are injectable, self-setting ceramic pastes generally known for their favorable bone response. Ingrowth of bone and subsequent degradation rates can be enhanced by the inclusion of macropores. Initial porosity can be induced by CO(2) foaming during setting of the cement, whereas secondary porosity can develop after hydrolysis of incorporated poly(DL-lactic- co-glycolic acid) (PLGA) microparticles. In this study, we focused on the biological response to porous PLGA/Ca-P cement composites. Pre-set composite discs of four formulations (4 wt% or 15 wt% PLGA microparticles and low or high CO(2) induced porosity) were implanted subcutaneously and in cranial defects in rats for 12 weeks. Histological analysis of the explanted composites revealed that bone and fibrous tissue ingrowth was facilitated by addition of PLGA microparticles (number average diameter of 66 +/- 25 microm). No adverse tissue reaction was observed in any of the composites. Significant increases in composite density due to bone ingrowth in cranial implants were found in all formulations. The results suggest that the PLGA pores are suitable for bone ingrowth and may be sufficient to enable complete tissue ingrowth without initial CO(2) induced porosity. Finally, bone-like mineralization in subcutaneous implants suggests that, under appropriate conditions and architecture, porous PLGA/Ca-P cement composites can exhibit osteoinductive properties. These PLGA/Ca-P composites are a promising scaffolding material for bone regeneration and bone tissue engineering.     

Restoration of segmental bone defects in rabbit radius by biodegradable capsules containing recombinant human bone morphogenetic protein-2

Recombinant human bone morphogenetic protein-2 (rhBMP-2) was encapsulated in biodegradable poly(DL-lactide-co-glycolide) (PLGA) capsules to regenerate bone by controlling the release rate of rhBMP-2. The rhBMP-2/PLGA capsules containing 12 microg of rhBMP-2 were implanted in seven 15-mm segmental defects of rabbits radii to examine the healing capacity of the rhBMP-2/PLGA capsules. For the control group, four segmental defects were left empty and two were implanted with ghost PLGA capsules. Healing of the defects was followed for 24 weeks and periodically evaluated by radiographs and histological examination. Mechanical testing was applied to three regenerated bone samples at 24 weeks postoperatively when the mature cortex was observed. Mechanical properties of regenerated bone were not significantly different from normal intact bone statistically. Histologically, the rhBMP-2/PLGA capsules disappeared completely during the process of bone regeneration. These results increased possibilities for clinical application of rhBMP-2/PLGA capsules.     

Comparative study of osteogenic potential of a composite scaffold incorporating either endogenous bone morphogenetic protein-2 or exogenous phytomolecule icaritin: an in vitro efficacy study

A local delivery system with sustained and efficient release of therapeutic agents from an appropriate carrier is desirable for orthopedic applications. Novel composite scaffolds made of poly (lactic-co-glycolic acid) with tricalcium phosphate (PLGA/TCP) were fabricated by an advanced low-temperature rapid prototyping technique, which incorporated either endogenous bone morphogenetic protein-2 (BMP-2) (PLGA/TCP/BMP-2) or phytomolecule icaritin (ICT) (PLGA/TCP/ICT) at low, middle and high doses. PLGA/TCP served as control. In vitro degradation, osteogenesis and release tests showed statistical differences among PLGA/TCP/ICT, PLGA/TCP and PLGA/TCP/BMP-2 groups, where PLGA/TCP/ICT had the desired slow release of bioactive icaritin in a dose-dependent manner, whereas there was almost no BMP-2 release from the PLGA/TCP/BMP-2 scaffolds. PLGA/TCP/ICT significantly increased more ALP activity, upregulated mRNA expression of osteogenic genes and enhanced calcium deposition and mineralization in rabbit bone marrow stem cells cultured on scaffolds compared with the other two groups. These results indicate the desired degradation rate, osteogenic capability and release property in PLGA/TCP/ICT composite scaffold, as icaritin preserved its bioactivity and structure after incorporation, while PLGA/TCP/BMP-2 did not show an initially expected osteogenic potential, owing to loss of the original bioactivity of BMP-2 during its incorporation and fabrication procedure. The results suggest that PLGA/TCP composite scaffolds incorporating osteogenic ICT might be a promising approach for bone tissue bioengineering and regeneration.     

Preparation and properties of poly(lactide-co-glycolide) (PLGA)/ nano-hydroxyapatite (NHA) scaffolds by thermally induced phase separation and rabbit MSCs culture on scaffolds

Biodegradable polymer/bioceramic composites scaffold can overcome the limitation of conventional ceramic bone substitutes such as brittleness and difficulty in shaping. To better mimic the mineral component and the microstructure of natural bone, novel nano-hydroxyapatite (NHA)/polymer composite scaffolds with high porosity and well-controlled pore architectures as well as high exposure of the bioactive ceramics to the scaffold surface is developed for efficient bone tissue engineering. In this article, regular and highly interconnected porous poly(lactide-co-glycolide) (PLGA)/NHA scaffolds are fabricated by thermally induced phase separation technique. The effects of solvent composition, polymer concentration, coarsening temperature, and coarsening time as well as NHA content on the micro-morphology, mechanical properties of the PLGA/NHA scaffolds are investigated. The results show that pore size of the PLGA/NHA scaffolds decrease with the increase of PLGA concentration and NHA content. The introduction of NHA greatly increase the mechanical properties and water absorption ability which greatly increase with the increase of NHA content. Mesenchymal stem cells are seeded and cultured in three-dimensional (3D) PLGA/NHA scaffolds to fabricate in vitro tissue engineering bone, which is investigated by adhesion rate, cell morphology, cell numbers, and alkaline phosphatase assay. The results display that the PLGA/NHA scaffolds exhibit significantly higher cell growth, alkaline phosphatase activity than PLGA scaffolds, especially the PLGA/NHA scaffolds with 10 wt.% NHA. The results suggest that the newly developed PLGA/NHA composite scaffolds may serve as an excellent 3D substrate for cell attachment and migration in bone tissue engineering.     

Orthotopic bone formation by implantation of apatite-coated poly(lactide-co-glycolide)/hydroxyapatite composite particulates and bone morphogenetic protein-2

Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. In the present study, we tested the suitability of apatite-coated poly(D,L-lactide-co-glycolide)/nanohydroxyapatite (PLGA/HA) particulates as carriers for the controlled release of BMP-2. The release of BMP-2 from apatite-coated PLGA/HA particulates was sustained for at least 4 weeks in vitro. A delivery system of apatite-coated PLGA/HA particulates suspended in fibrin gel further slowed the BMP-2 release rate. In vivo implantation of either Fibrin gel + BMP-2 or Fibrin gel + apatite-coated PLGA/HA particulates showed enhanced new bone formation in critical-sized calvarial defects of rats 8 weeks after implantation, compared to implantation of fibrin gel only. Importantly, new bone formation was much higher in the defects treated with BMP-2 delivery using apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + PLGA/HA + BMP-2 group) than in the defects treated either with apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + BMP-2 group) or with BMP-2 delivery using fibrin gel alone (Fibrin gel + BMP-2 group). BMP-2 and osteoinductive HA had an additive effect on orthotopic bone formation. In conclusion, the apatite-coated PLGA/HA particulates showed good results as carriers for BMP-2. The BMP-2 delivery system showed high osteogenic capability in a rat calvarial bone defect model. The local and sustained delivery system for BMP-2 developed in this study may be useful as a carrier for BMP-2 and would enhance bone regeneration efficacy for the treatment of large bone defects.     

CaSiO₃ microstructure modulating the in vitro and in vivo bioactivity of poly(lactide-co-glycolide) microspheres

Poly(lactide-co-glycolide) (PLGA) microspheres have been used for regenerative medicine due to their ability for drug delivery and generally good biocompatibility, but they lack adequate bioactivity for bone repair application. CaSiO? (CS) has been proposed as a new class of material suitable for bone tissue repair due to its excellent bioactivity. In this study, we set out to incorporate CS into PLGA microspheres to investigate how the phase structure (amorphous and crystal) of CS influences the in vitro and in vivo bioactivity of the composite microspheres, with a view to the application for bone regeneration. X-ray diffraction (XRD), N? adsorption-desorption analysis, and scanning electron microscopy (SEM) were used to analyze the phase structure, surface area/pore volume, and microstructure of amorphous CS (aCS) and crystal CS (cCS), as well as their composite microspheres. The in vitro bioactivity of aCS and cCS-PLGA microspheres was evaluated by investigating their apatite-mineralization ability in simulated body fluids (SBF) and the viability of human bone mesenchymal stem cells (BMSCs). The in vivo bioactivity was investigated by measuring their de novo bone-formation ability. The results showed that the incorporation of both aCS and cCS enhanced the in vitro and in vivo bioactivity of PLGA microspheres. cCS/PLGA microspheres improved better in vitro BMSC viability and de novo bone-formation ability in vivo, compared to aCS/PLGA microspheres. Our study indicates that controlling the phase structure of CS is a promising method to modulate the bioactivity of polymer microsphere system for potential bone tissue regeneration.     

携载rhBMP-2微球的新型复合人工骨的制备及生物相容性研究

目的制备一种具有良好生物相容性、降解性和成骨活性、可注射的自凝固新型骨修复材料。方法采用复乳溶剂挥发方法制备携载rhBMP-2的聚乳酸与聚乙醇酸共聚物（PLGA）微球，并将其与rhBMP-2／磷酸钙骨水泥（CPC）复合，制备出rhBMP-2／PLGA微球／CPC复合人工骨。探讨材料特性包括形貌和体外rhBMP-2释放速度，采用体外细胞培养的方法测定复合材料的细胞黏附能力及其浸提液对于人骨髓基质干细胞（MSCs）增殖和成骨分化的影响。结果与单纯rhBMP-2／CPC材料相比较，复合材料rhBMP-2体外释药明显提高。材料与MSCs可良好黏附并使其增殖。体外培养时材料不同时间的浸提液对MSCs细胞的增殖具有促进作用，对于细胞成骨分化的影响与单纯CPC无明显差别。结论rhBMP-2／PLGA微球／磷酸钙骨水泥新型复合人工骨具有良好的生物相容性和活性因子缓释功能，是一种有良好应用前景的骨修复材料。     

Carbon Nanotube–Poly(lactide-co-glycolide) Composite Scaffolds for Bone Tissue Engineering Applications

Despite their indisputable clinical value, current tissue engineering strategies face major challenges in recapitulating the natural nano-structural and morphological features of native bone. The aim of this study is to take a step forward by developing a porous scaffold with appropriate mechanical strength and controllable surface roughness for bone repair. This was accomplished by homogenous dispersion of carbon nanotubes (CNTs) in a poly(lactide-co-glycolide) (PLGA) solution followed by a solvent casting/particulate leaching scaffold fabrication. Our results demonstrated that CNT/PLGA composite scaffolds possessed a significantly higher mechanical strength as compared to PLGA scaffolds. The incorporation of CNTs led to an enhanced surface roughness and resulted in an increase in the attachment and proliferation of MC3T3-E1 osteoblasts. Most interestingly, the in vitro osteogenesis studies demonstrated a significantly higher rate of differentiation on CNT/PLGA scaffolds compared to the control PLGA group. These results all together demonstrate the potential of CNT/PLGA scaffolds for bone tissue engineering as they possess the combined effects of mechanical strength and osteogenicity.