功能聚乳酸改性羟基磷灰石有机无机复合材料的制备

随着科技的进步,医学水平在不断提高,医用材料越来越受到广泛的重视,其中利用人工骨替代材料来修复、替代骨缺损成为医学骨科领域的研究重点。首先在羟基磷灰石表面引入活性醛基,通过活性醛基将聚乳酸基聚合物接枝到羟基磷灰石表面,改善羟基磷灰石与聚合物复合时,分布不均,相界面结合不牢的缺点,再将经过聚乳酸基聚合物改性的羟基磷灰石与聚乳酸-羟基乙酸共聚物通过超重力技术强力混合,制备骨修复材料。复合材料的吸水率为2.9%,拉伸强度为52.62 MPa,弯曲强度为87.348 MPa。     

纳米羟基磷灰石/聚酰胺复合材料的制备及在骨修复中的应用研究

为总结近几年来有关纳米羟基磷灰石/聚酰胺复合物的制备方法以及在骨修复研究上的应用.以纳米羟基磷灰石/聚酰胺为关键词,从各类期刊数据库中检索有关纳米羟基磷灰石/聚合物的制备方法和应用的文献,总共查阅得到文献80篇.结果显示:纳米羟基磷灰石/聚酰胺复合物的制备方法主要有三种,均能制备出生物相容性良好的高韧性复合物,并且纳米羟基磷灰石/聚酰胺复合物在骨修复技术上得到了广泛应用.论述了纳米羟基磷灰石/聚酰胺复合材料的制备方法,以及该复合材料的生物相容性研究和在骨修复临床中的应用进展.     

纳米羟基磷灰石/聚酰胺复合材料的制备及骨修复中的应用研究

为总结近几年来有关纳米羟基磷灰石/聚酰胺复合物的制备方法以及在骨修复研究上的应用。以纳米羟基磷灰石/聚酰胺为关键词,从各类期刊数据库中检索有关纳米羟基磷灰石/聚合物的制备方法和应用的文献,总共查阅得到文献80篇。结果显示:纳米羟基磷灰石/聚酰胺复合物的制备方法主要有三种,均能制备出生物相容性良好的高韧性复合物,并且纳米羟基磷灰石/聚酰胺复合物在骨修复技术上得到了广泛应用。论述了纳米羟基磷灰石/聚酰胺复合材料的制备方法,以及该复合材料的生物相容性研究和在骨修复临床中的应用进展。     

细菌纤维素组织工程支架的仿生矿化研究

骨骼创伤已经成为当今影响人类健康的一大病症。因此,骨修复材料就成为研究的一大热点。骨组织工程支架作为重要的骨修复材料,可以诱导成骨细胞生长并为新骨生长提供条件。传统的骨组织工程支架包括合成高分子(如聚乳酸、聚乙醇酸等)和天然高分子(如胶原、壳聚糖等)。与传统支架材料相比,细菌纤维素(BC)具有良好的生物相容性、精细的纳米空间三维网络结构,有作为组织工程支架的潜能。通过仿生矿化处理,BC纳米纤维表面可以生长出羟基磷灰石(HA)的晶体颗粒,且HA颗粒均匀覆盖在纳米纤维表面。通过热分析得出,仿生矿化处理会使BC的热稳定性得到一定的提升。     

不同制备方法对C（f）／CS-HA复合材料力学性能的影响

以壳聚糖-羟基磷灰石（CS-HA）为基体,碳纤维为增强相,采用原位杂化、原位共混的方法,制备了短碳纤维增强CS-HA生物复合材料．研究了制备方法对复合材料性能的影响．采用万能材料试验机、扫描电子显微镜和X-射线衍射分别对材料的抗折强度和断面的微观形貌等进行了测试和表征．结果表明,用原位杂化方法制备的纳米复合材料的力学性能优于共混制备样品的力学性能,平均高10～20MPa．当HA／CS为0．1时,采用原位复合方法制备的复合材料的弯曲强度达到了62．57MPa．     

丝素蛋白-聚乙烯醇复合凝胶对骨组织工程支架性能的影响

组织工程骨支架材料及制备对支架性能影响至关重要。同单一聚乙烯醇凝胶相比,丝素蛋白-聚乙烯醇复合凝胶不仅可以增加支架所承受应力而且可以提高支架韧性。研究证明,使用水浴加热方法,将丝素蛋白粉末与聚乙烯醇晶粒按照1∶4混合加热,制成丝素蛋白-聚乙烯醇复合凝胶。再与羟基磷灰石充分混合,基于低温冷冻干燥技术,制备成试验试样。压缩试验测量最大压缩强度为31.2 MPa,弹性模量为11.07 MPa,最大总变形低于单一聚乙烯醇/羟基磷灰石试样,且压缩时不易发生断裂及粉碎,综合力学性能较好。电镜实验观察得到羟基磷灰石/丝素蛋白-聚乙烯醇复合材料试样孔径为15~350μm,微孔分布均匀且连通性较好。水浴加热后的丝素蛋白-聚乙烯醇(1∶4)复合凝胶与羟基磷灰石按照1.5∶1混合时,3D打印复合材料支架成形好,无丝材膨胀,孔隙明显。使用此方法制备的羟基磷灰石/丝素蛋白-聚乙烯醇复合材料,力学性能及孔径大小利于负重部位骨缺损修复及骨细胞的生长。     

三维丝素蛋白/羟基磷灰石支架的生物学性能

综合运用丝素蛋白纤维网的非编织制作方法和仿生矿化法,构建三维多孔丝素蛋白/纳米羟基磷灰石复合支架.通过体外蛋白酶降解和成骨细胞培养,对支架材料的生物学性能进行初探.发现蛋白酶对丝素蛋白降解的作用大小依次为,蛋白酶K＞胰蛋白酶＞α-糜蛋白酶＞Ⅰ型胶原酶.所构建的支架显示出良好的生物相容性并能促进成骨细胞生长和分化.三维多孔丝素蛋白/纳米羟基磷灰石支架可望成为新型有机/无机复合生物材料,为骨组织工程支架的设计提供了新的思路.     

PLA纤维增强HA/CS复合材料的制备与改性研究

采用半透性模具以原位沉析法制备了聚乳酸纤维增强的羟基磷灰石/壳聚糖(f(PLA)-HA/CS)复合板材,研究了纤维掺杂量以及戊二醛交联对复合材料性能的影响。通过红外吸收光谱、X-射线衍射、扫描电子显微镜等表征了材料结构与性能的关系。分析表明,复合物中生成了弱结晶态的羟基磷灰石,聚乳酸纤维与基体形成了较好的界面结合,材料的抗折强度明显增强,强度值随纤维量的增加先增后降,采用戊二醛交联可进一步提高复合物的抗折强度,可生产一类潜在的可完全降解型骨科材料。     

纳米羟基磷灰石/壳聚糖载药微球的制备及性能

以纳米羟基磷灰石和壳聚糖为基质,构建一种新型甲硝唑缓释微球,作为充填材料用于骨修复.利用乙醇为反应溶剂,聚丙烯酸为分散剂,在pH=11的条件下,制备针状纳米羟基磷灰石.采用W/O型反相乳化-交联技术制备羟基磷灰石/壳聚糖载甲硝唑复合微球.通过紫外分光光度法测定甲硝唑含量和体外累积释放度.研究结果表明:制得的羟基磷灰石/壳聚糖载药复合微球粒径主要集中在1～10 μm,壳聚糖对羟基磷灰石和甲硝唑形成了很好的包覆.复合微球平均载药量为38.23%,平均包封率为54.21%,3 d内对甲硝唑的释放达到82%左右.所制备的羟基磷灰石/壳聚糖载药复合微球形态圆整,粒径分布较为均匀,对甲硝唑具有较好的缓释效果.     

羟基磷灰石/丝蛋白复合骨材料的生物相容性

以共沉淀法制备了羟基磷灰石/丝蛋白(HA/SF)复合骨修复材料,并对材料进行了XRD、TEM、SEM、孔径分布和孔隙率等相关的测试和表征。结果表明:该复合材料的无机组分为20~30 nm长、5 nm宽的棒状羟基磷灰石(HA)结晶,这些晶粒沿c轴自组装团聚成簇分散在丝蛋白基质中形成三维多孔结构,其孔径分布在0.3~115μm之间,开口孔隙率达66%。该材料植入动物体内,未出现明显的排异反应,在植入部位有连续的骨性连接和新生骨形成,说明HA/SF复合材料具有良好的生物相容性和骨诱导活性。     

A study on in vitro and in vivo bioactivity of nano hydroxyapatite/polymer biocomposite

When bioactive materials are implanted in vivo, a bone-like apatite layer can be found on their surfaces, which is critical to the establishment of bone-bonding between materials and living tissues. In this study, bone-like apatite formation in vitro and in vivo on surface of nano apatite/polyamide (n-HA/PA66) composite was investigated, and the interface between the implanted composite and surrounding bone tissue of rabbit were also examined. The results revealed that in both simulated body fluids (SBF) and dorsal muscles of rabbit, bone-like apatite could form on the biocomposite surface. When the samples were implanted in cortical bone, they combined directly with the natural bone without fibrous tissue in-between. The results showed that the n-HA/PA66 biocomposite had excellent bioactivity, which might be a good candidate for bone defect replacement.     

Dexamethasone-Loaded PLGA Microspheres Incorporated PLLA/PLGA/PCL Composite Scaffold for Bone Tissue Engineering

The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.     

磷酸钙与胶原双相多级仿生骨组织工程支架研究

磷酸钙与胶原是天然骨组织的重要组成成分,介绍了一种仿生设计磷酸钙与胶原双相复合的多级仿生骨组织支架.采用双氧水发泡技术精确定制磷酸钙支架孔结构,结合真空灌注胶原以及仿生矿化技术,构建磷酸钙,胶原双相多级仿生骨组织支架,材料的孔结构及化学组分可实现定制设计.通过对支架材料测试表征,结果显示,这种无机/有机/无机多级仿生支架材有良好的力学性能.材料的体外细胞实验结果证实,这种多级仿生支架材料具有良好的生物相容性.     

Haversian bone-mimicking bioceramic scaffolds enhancing MSC-macrophage osteo-imunomodulation

The interaction between immune cells and bone forming cells plays a vital role in maintaining the homeostasis of the skeletal system, and is regulated by the three-dimensional structure of tissues. Whether the construction of biomaterials can activate or reproduce this spatial “cross-talk” between immune cells and bone forming cells in bone natural formation process is a prerequisite for successful fracture healing and bone regeneration. Herein, a bone marrow mesenchymal stem cells (MSCs)/macrophages-laden Haversian bone-mimicking bioceramic scaffold was successfully prepared through the biomimetic design of biomaterials and 3D printing technology. MSCs and macrophages were respectively distributed in the cancellous bone and Haversian canals of the scaffold to simulate the three-dimensional structure regulation of the cell spatial distribution and multiple intercellular interaction in natural bone tissue, and worked in concert to modulate the scaffold material-mediated osteo-immune microenvironment. The in vitro study revealed that the pro-inflammatory response of macrophages was more significantly inhibited when distributed with MSCs in the scaffolds at a cell ratio of 0.5:1 for co-culture, in comparison with multicellular culture at other ratios and unicellular culture. Meanwhile, MSCs exhibited the relatively high osteogenic potential, most likely via the activation of certain key signaling pathways mediated by macrophages-derived paracrine signaling mediators (OSM, BMP-2, and WNT10b). This work not only establishes a bionic platform for the regulation of multicellular osteo-immune response and regeneration but also offers a promising tissue-engineered biomimetic scaffold with improved immunomodulatory function for promoting bone tissue regeneration.     

Nanofibrous Scaffold Containing Osteoblast-Derived Extracellular Matrix for the Proliferation of Bone Marrow Mesenchymal Stem Cells

Extracellular matrix( ECM) plays a prominent role in establishing and maintaining an appropriate microenvironment for tissue regeneration. The aims of this study were to construct a tissue engineered scaffold by reconstituting osteoblast cell-derived ECM( O-ECM) on the electrospun nanofibrous scaffold,and further to evaluate its subsequent application for promoting the proliferation of bone marrow mesenchymal stem cells( BMSCs). To engineer a biomimetic scaffold, calvarial osteoblasts and electrospun poly-llactic acid( PLLA) nanofibers were prepared and subjected to decellularize for O-ECM deposition. To evaluate and characterize the O-ECM/PLLA scaffold, the morphology was examined and several specific mark proteins of osteoblasts matrix were evaluated.Furthermore,the cell counting kit-8( CCK-8) assay was used to detect the proliferation of the BMSCs cultivated on the O-ECM/PLLA scaffold. The results indicated O-ECM/PLLA scaffold was loaded with Collagen I, Fibronectin, and Laminin, as the composition of the marrow ECM. After decellularization,O-ECM deposition was observed in O-ECM/PLLA scaffold. Moreover,the O-ECM/PLLA scaffold could significantly enhance the proliferation of BMSCs,suggesting better cytocompatibility compared to the other groups tested. Taken together,a biomimetic scaffold based on the joint use of O-ECM and PLLA biomaterials,which represents a promising approach to bone tissue engineering, facilitates the expansion of BMSCs in vitro.     

Injectable Premixed Cement of Nanoapatite and Polyamide Composite

A new type of injectable premixed bone cement consisting of nano-hydroxyapatite (n-HA) and polyamide 66(PA66) composite is investigated.This cement can be handled as paste and easily shaped.which can set in air,in physiological saline solution and in blood.The setting time,injectability and compressive strength of the cement largely depend on the ration of liquid to powder (L/P),Moreover,the content of n-HA in composite also affects the compressivce strength and injectability of the cement.The premixed composite cement can remain stable in the package for a long period and harden only after delivery to the defects site.The results suggest that injectable premixed cement has a reasonable setting time,reasonable viscosity for injecting,excellent washout resistance and high mechaical strength,which can be developed for root canal filling,sealing and various bone defects augmentation.     

纳米羟基磷灰石对两种药物的载药性能研究

骨缺损常常伴随着炎症、肿瘤等情况,以各种骨修复材料为载体的药物缓释体系是一种新型的给药方式.以纳米羟基磷灰石(n-HA)为载药体系,用红外光谱和透射电镜表征了n-HA的结构,考察了其对抗生素阿莫西林和抗肿瘤药鬼臼毒素的不同吸附作用,并研究其对抗生素阿莫西林吸附量的影响.实验结果表明,n-HA的红外图谱及粒径与人体骨颇为接近,同时n-HA可以吸附有羟基的阿莫西林,并且吸附性能随着阿莫西林初始浓度的不同而不同,吸附速度快,4 h达到吸附平衡;但是对没有特征基团的鬼臼毒素,n-HA不能吸附.n-HA这种对有某些特征基团分子的特异性吸附作用,对载药骨材料的研究具有非常重要的指导意义.     

Incorporation of Sphingosine 1-Phosphate Loaded Mesoporous Silica Nanoparticles into Poly( L-lactic acid ) Nanofibrous Scaffolds for Bone Tissue Engineering

Controlled release of the functional factors is the key to improve clinical therapeutic efficacy during the tissue repair and regeneration.The three-dimensional(3D)scaffold can provide not only physical properties such as high strength and porosity but also an optimal environment to enhance tissue regeneration.Sphingosine1-phosphate(S1P),an angiogenic factor,was loaded into mesoporous silica nanoparticles(MSNs)and then incorporated into poly(L-lactic acid)(PLLA)nanofibrous scaffold,which was fabricated by thermally induced phase separation(TIPS)method.The prepared scaffolds were examined by attenuated total reflection Fourier transform infrared spectroscopy(ATR-FTIR),scanning electron microscopy(SEM),and transmission electron microscopy(TEM)and compressive mechanical test.The ATR-FTIR result demonstrated the existence of MSNs in the PLLA nanofibrous scaffold.The SEM images showed that PLLA scaffold had regular pore channel,interconnected pores and nanofibrous structure.The addition of MSNs at appropriate content had no visible effect on the structure of scaffold.The compressive modulus of scaffold containing MSNs was higher than that of the scaffold without MSNs.Furthermore,fluorescein isothiocyanate(FITC)was used as model molecule to investigate the release behavior of S1P from MSNsincorporated PLLA(MSNs/PLLA)nanofibrous scaffold.The result showed that the composite scaffold largely reduced the initial burst release and exhibited prolonged release of FITC than MSNs.Thus,these results indicated that S1P-loaded composite nanofibrous scaffold has potential applications for bone tissue engineering.     

Preparation and evaluation of biomimetric nano-hydroxyapatite-based composite scaffolds for bone-tissue engineering

In the present study,novel biomimetic composite scaffolds with a composition similar to that of natural bone were prepared,using nano-hydroxyapatite,collagen,and phosphatidylserine.The scaffolds possess an interconnected porous structure with a porosity of 84%.The pore size ranges from several micrometers up to about 400 m.In-vitro studies in simulated body fluids showed that the morphologies of the products derived from mineralization can be regulated by the extracellular matrix components of the scaffolds;this in turn leads to creation of a large number of hydroxyapatite crystals on the scaffold surface.The regulatory properties of collagen and phosphatidylserine also influenced the cell response to the composite scaffolds.MC3T3-E1 cells attached and spread on the surfaces of the materials and interacted with the substrates;this may be the result of charged groups on the composite materials.Radiological analysis suggested that calluses and bone bridges formed in defects within 12 weeks.These composite scaffolds may therefore be a suitable replacement in bone-tissue engineering.