纳米羟基磷灰石/聚合物多孔复合支架材料

为提高骨组织工程支架材料的力学性能,改善其生物活性,综合天然与合成高分子的优点,采用溶液共混相分离法制备出聚己内酯(PCL)-壳聚糖(CS)多孔支架材料, 并进一步采用离心注浆法填充具有生物活性的纳米羟基磷灰石(HA)-聚乙烯醇(PVA)复合浆料, 制备了n-HA-PVA/PCL-CS复合多孔支架材料, 改善了PCL-CS支架材料力学性能。采用扫描电子显微镜、红外光谱、元素分析、孔隙率和抗压强度试验对材料进行了表征。结果表明, PCL-CS支架材料的内部具有蜂窝状的相互贯通的孔隙结构,孔隙率可以达到60%～80%。CS含量越大,孔隙率越大,而抗压强度越小。填充后的n-HA-PVA/PCL-CS复合多孔支架材料,孔隙率有所下降,但仍大于60%,而其弹性模量可提高至25.71 MPa。      

浸没凝胶相分离法制备聚己内酯多孔支架

为了制备结构和性能满足骨组织工程支架要求的聚己内酯(PCL)多孔支架材料,采用浸没凝胶相分离法,以冰醋酸和丙酮为混合溶剂,水为凝固剂,壳聚糖(CS)颗粒为添加剂制得一系列PCL多孔支架。探讨了溶剂组成、PCL浓度、CS添加量对PCL多孔支架结构和性能的影响。结果表明:添加CS颗粒有利于形成多孔三维支架,随着CS含量的增加,孔隙率略微下降,抗压强度提高。随着PCL质量分数的增加,孔隙率明显下降,但抗压强度增大。当溶剂组成中丙酮含量为50 wt%~60 wt%,PCL质量分数不高于10 wt%时,通过改变CS用量,可制得孔隙率和力学性能满足骨组织工程要求的相互贯通的三维多孔支架材料。     

壳聚糖/聚己内酯复合膜的微观形态与结构特征

以性能优异的生物可降解高分子聚己内酯（PCL）与壳聚糖（CS）进行冰醋酸酸溶复合,并采用流延法制备CS∶PCL质量比分别为0∶100、5∶95、10∶90、15∶85、20∶80、100∶0的CS/PCL复合膜,通过XRD、FTIR、1HNMR、SEM及AFM对复合膜进行了微观形态与结构表征。结果表明:PCL与CS具有良好的相容性,二者分子间形成了较强的氢键,且伴有PCL端位羧基与CS侧链羟基反应生成了新的化学键,使CS/PCL复合膜结构稳定。CS/PCL复合膜的复合比对其结构特征及微观形态影响较大。CS/PCL（10∶90）复合膜的结晶度为29.97%,孔隙率达到85.61%,呈现表面防渗漏、内部多孔且连通的微观结构,初步确定10∶90为二者的最佳复合比。不同复合比的CS/PCL复合膜的微观形态与结构分析为其开发、应用提供了重要的理论依据。      

壳聚糖/羟基磷灰石表面修饰聚己内酯多孔骨支架的制备及性能

采用选择性激光烧结技术构建多孔聚己内酯(PCL)骨支架,用原位合成的方法制得壳聚糖/羟基磷灰石(CS/HA)悬浮液,并采用真空浸泡、低速离心和冷冻凝胶的方法使CS/HA黏附在PCL支架的表面,以改善骨支架的生物相容性和细胞增殖活性。通过X射线衍射(XRD)和扫描电子显微镜(SEM)观测复合支架的物相和形貌,测量支架的压缩强度和杨氏模量,测量支架表面的水接触角,并通过体外细胞实验研究复合支架的生物学性能。实验结果表明,原位合成的方法制得了羟基磷灰石(HA);CS/HA凝胶与PCL骨支架表面黏附良好;CS/HA改善了PCL支架表面的亲水性,提升了骨支架的生物相容性和细胞增殖活性。     

分级多孔壳聚糖/聚乳酸复合支架的制备及骨修复性能

为了仿生莲藕内部的贯穿大孔结构,以生物相容性好的壳聚糖(CS)作为基质材料,利用冰粒致孔、石蜡模具和冰模具成型3种成型方法制备了分级多孔CS支架材料,然后与力学强度较高的聚乳酸(PLLA)复合,制备网络互穿CS/PLLA复合支架。通过SEM、压缩强度测试和兔股骨髁骨缺损模型对CS/PLLA复合材料的形貌、力学强度和骨修复性能进行了表征。结果表明:利用冰模具制备的CS/PLLA复合支架能可控、批量制备,具有微米-毫米分级多孔结构,大孔孔径约为2mm,内部均匀分布着孔径约为60μm的贯穿微孔,并在微孔内形成密集的PLLA絮状网络结构。干态复合材料的压缩强度和模量分别比纯CS支架的提高了6倍和15倍。体内植入实验结果表明,CS/PLLA复合材料能够促进骨缺损的愈合,并随着新骨的形成,复合材料逐渐被降解吸收。     

Preparation and characterization of nano-hydroxyapatite/polymer composite scaffolds

Polycaprolactone/chitosan (PCL/CS) porous composite scaffolds were prepared by solution phase separation method, and the scaffolds were further enhanced by filling with nano-hydroxyapatite/polyvinyl alcohol (n-HA/PVA) composite slurry to prepare n-HA-PVA/PCL-CS composite porous scaffolds through slurry centrifugal filling technique. The morphology, microstructure, component, porosity and mechanical property of the scaffolds were characterized using scanning electron microscope, X-ray diffraction, Fourier transform infrared spectroscope, elemental analyzer and material test machine. The results show that PCL/CS scaffolds have mutual transfixion porous structure just like honeycombs. The porosity of the scaffolds can achieve 60-80%. As the content of CS increases, the porosity increases while the compressive strength decreases. After filled with HA/PVA composite slurry, the porosity of n-HA/PCL-CS composite scaffolds decreases, but still greater than 60%, while the compression modulus can increase to 25.7 MPa.     

壳聚糖/磷灰石-硅灰石复合多孔支架材料的制备与性能

以磷灰石-硅灰石(AW)生物活性多孔玻璃陶瓷支架材料为基体,采用物理包被法制备了壳聚糖(CS)/AW复合多孔支架材料,通过红外图谱分析、扫描电镜、光学显微镜、强度检测等分析测试方法,研究了复合材料的组成、微观结构、力学和矿化性能。结果发现：复合材料与AW多孔支架材料基体相比,仍具有三维贯通且分布均匀的孔隙结构,孔径尺寸约 100～500μm,孔隙率为80%左右,且力学性能明显增强,平均抗压强度可达3.11 MPa,比多孔AW支架材料基体的平均抗压强度提高了8.3倍。体外模拟体液浸泡实验表明,复合材料具有较高的矿化功能,预示材料具有较好的生物活性。这种复合材料可望作为人体非承重部位的植入骨修复体和组织工程支架使用。     

多孔n-HA/CS/PA66三元复合支架材料的制备及性能

采用常压共混复合法制备了纳米羟基磷灰石/壳聚糖/聚酰胺66(n-HA/CS/PA 66)三元复合材料,并以乙醇为溶剂,聚乙烯吡咯烷酮和氯化钠混合物为致孔剂的粒子沥滤法制备了n-HA/CS/PA 66三元复合多孔支架材料,用燃烧试验、IR、XRD、SEM、孔隙率及力学性能测试等手段对其进行了表征。结果表明,n-HA在复合材料中分布均匀且呈弱结晶状态,复合前后三组分的化学组成未发生显著变化,但三相间两两均发生了相互作用。在制备n-HA/CS/PA 66多孔材料时,加入少量的聚乙烯吡咯烷酮可使该多孔材料孔隙率更高,孔的贯通性更好。     

原位自发泡制备磷酸钙/聚氨酯复合骨修复支架

磷酸钙/聚氨酯(CaP/PU)复合骨修复支架制备过程中随着材料体系粘度逐渐增大, 后期加入的发泡剂难于均匀分散, 影响支架孔隙率及孔结构均匀性。本研究在CaP/PU材料合成过程中将发泡剂水以磷酸氢钙结晶水合物(DCPD)的形式均匀复合在材料中, 在一定条件下释放结晶水与聚氨酯(PU)中的异氰酸根反应生成CO₂, 实现自发泡成型。实验结果显示, 90 ℃条件下自发泡制备的CaP/PU支架孔隙率高、孔结构均匀、贯通性好。将90 ℃发泡成型的CaP/PU多孔支架在110 ℃再熟化处理, 可提高支架的力学性能高达1倍以上。该方法简便易行, 为聚氨酯基多孔支架的制备提供了新思路。     

骨组织工程用纳米羟基磷灰石/ 壳聚糖多孔支架材料的制备及性能表征

以16.7%(质量分数)的柠檬酸水溶液作溶剂,通过粒子沥滤法制备了 n HA/CS多孔材料,并对其进行了IR、XRD、SEM、孔隙率及力学性能测试。结果表明n HA/CS复合材料中羟基磷灰石呈弱结晶状态,复合前后两组分的化学组成未发生显著变化,但两相间发生了相互作用。多孔材料呈高度多孔结构,孔壁上富含微孔,孔间贯通性高;复合材料/致孔剂质量比为1时,多孔材料的孔隙率为 53%,其抗压强度可达17 MPa左右,可以满足组织工程支架材料的要求。     

Fabrication of hydroxyapatite-poly(<Emphasis Type="Italic">ε</Emphasis>-caprolactone) scaffolds by a combination of the extrusion and bi-axial lamination processes

Hydroxyapatite (HA)/poly(ε-caprolactone) (PCL) composite scaffolds were fabricated using a combination of the extrusion and bi-axial lamination processes. Firstly, HA/PCL composites with various HA contents (0, 50, 60, 70 wt%) were prepared by mixing the HA powders and the molten PCL at 100 °C and then extruded through an orifice with dimensions of 600 × 600 μm to produce HA/PCL composite fibers. Isobutyl methacrylate (IBMA) polymer fiber was also prepared in a similar manner for use as a fugitive material. The 3-D scaffold was then produced by the bi-axial lamination of the HA/PCL and IBMA fibers, followed by solvent leaching to remove the IBMA. It was observed that the HA/PCL composites had a superior elastic modulus and biological properties, as compared to the pure PCL. The fabricated HA/PCL scaffold showed a controlled pore structure (porosity of ∼49% and pore size of ∼512 μm) and excellent welding between the HA/PCL fibers, as well as a high compressive strength of ∼7.8 MPa.     

Fabrication and biocompatibility of nano non-stoichiometric apatite and poly(ε-caprolactone) composite scaffold by using prototyping controlled process

Nano biocomposite scaffolds of non-stoichiometric apatite (ns-AP) and poly(ε-caprolactone) (PCL) were prepared by a prototyping controlled process (PCP). The results show that the composite scaffolds with 40 wt% ns-AP contained open and well interconnected pores with a size of 400–500 μm, and exhibited a maximum porosity of 76%. The ns-AP particles were not completely embedded in PCL matrix while exposed on the composite surface, which might be useful for cell attachment and growth. Proliferation of MG₆₃ cells was significantly better on the composite scaffolds with porosity of 76% than that those with porosity of 53%, indicating that the scaffolds with high porosity facilitated cell growth, and could promote cell proliferation. The composite scaffolds were implanted into rabbit thighbone defects to investigate the in vivo biocompatibility and osteogenesis. Radiological and histological examination confirmed that the new bony tissue had grown easily into the entire composite scaffold. The results suggest that the well-interconnected pores in the scaffolds might encourage cell proliferation, and migration to stimulate cell functions, thus enhancing bone formation in the scaffolds. This study shows that bioactive and biocompatible ns-AP/PCL composite scaffolds have potential applications in bone tissue engineering.     

具有复杂形状的聚ε-己内酯多孔支架的模压制备方法

通过聚ε-己内酯(PCL)支架的制备，尝试了一种制备具有复杂形状的组织工程三雏多孔支架的新方法一改进的模压／粒子浸出法，并对所得外耳状多孔支架的形态、孔结构和孔隙率进行了表征。模压针对聚ε-己内酯熔体和大量盐粒的混合物进行。该方法所得支架孔隙率高达90％以上。可望用于各种不同复杂形状的三雏多孔支架的制备。     

Electrospun bioactive nanocomposite scaffolds of polycaprolactone and nanohydroxyapatite for bone tissue engineering

Nanocomposite scaffolds based on nanofibrous poly(epsilon-caprolactone) (PCL) and nanohydroxyapatite (nanoHA) with different compositions (wt%) were prepared by electrostatic co-spinning to mimic the nano-features of the natural extracellular matrix (ECM). NanoHA was found to be well dispersed in polymers up to the addition of 20 wt%, after ultrasonication. The composite scaffolds were characterized for structure and morphology using XRD, EDX, SEM, and DSC. The scaffolds have a porous nanofibrous morphology with fibers (majority) having diameters in the range of 450-650 nm, depending on composition, and interconnected pore structures. SEM, EDX, and XRD analyses have confirmed the presence of nanoHA in the fibers. As the nanoHA content in the fibers increases, the surface of fibers becomes rougher. The mechanical (tensile) property measurement of the electrospun composites reveals that as the nanoHA content increases, the ultimate strength increases from 1.68 MPa for pure PCL to 2.17, 2.65, 3.91, and 5.49 MPa for PCL/nanoHA composites with the addition of 5, 10, 15, and 20 wt% nanoHA, respectively. Similarly the tensile modulus also increases gradually from 6.12 MPa to 21.05 MPa with the increase of nanoHA content in the PCL/nanoHA fibers, revealing an increase in stiffness of the fibers due to the presence of HA. DSC analysis reveals that as nanoHA in the composite scaffolds increases, the melting point slightly increases due to the good dispersion and interface bonding between PCL and nanoHA.     

骨修复用聚磷酸钙/壳聚糖复合材料的合成及其细胞相容性

采用自行设计的悬浮液热分散复合法, 用硬脂酸(Sad)作为致孔剂, 通过复合-沉析-浸溶-漂洗-干燥的工艺制备大孔聚磷酸钙/壳聚糖(CPP/CS)复合材料棒材。将复合悬液滴入凝固液中, 经浸泡-漂洗-干燥的工艺制备CPP/CS微孔复合材料颗粒。用红外光谱及扫描电镜对复合材料进行了表征。实验表明, 合成的复合材料中CS的氨基和CPP的P O基生成了氢键, 其形态结构致密均匀, 大孔复合材料棒材的孔径为50~300μm, 孔隙率为71.13%; 微孔复合材料颗粒的孔径为10~100μm, 孔隙率为40.76%。研究了2种工艺不同配比复合材料的细胞相容性, 发现: 大孔复合材料棒材的细胞相容性比微孔复合材料颗粒好, 复合材料中随着CPP含量的增加, 细胞相容性增加, 当复合材料中CPP和CS的质量比为7/3时, 复合材料的细胞相容性较好。CPP与CS复合可以提高其压缩强度, 原料质量配比为CPP/CS＝7/3时, 复合材料的强度最高。      

壳聚糖/聚己内酯-聚乳酸多孔支架制备和表征

为调控骨组织工程支架的力学性能和降解性能,采用相分离方法,以冰醋酸-水为共溶剂配制聚合物溶液,以NaOH溶液为凝固剂,以CS为添加剂制备壳聚糖(CS)/聚己内酯(PCL)-聚乳酸(PLA)三维多孔支架,研究了聚合物质量比对支架结构、形貌、孔隙率、力学性能和降解性能的影响。实验结果表明,CS和基体存在相互作用,CS有利于形成三维相互贯通的微孔结构,但CS的存在会使基体中各组分的熔点降低。随着PCL和PLA用量比例的改变,孔径范围和微孔形貌发生了一系列的变化。当PCL∶PLA为2∶4和3∶3时,所制备的支架孔隙率均大于90%,当进一步增大PCL质量比时,孔隙率迅速下降。抗压测试表明,所制备的支架弹性模量为0.8～8.0 MPa。降解性能分析表明,4周以后,当PCL∶PLA为3∶3时,质量损失率最大,达到5.94%。该分析表明采用相分离法,通过调节PCL和PLA的质量比可制备形貌、孔隙率、降解速率和力学性能满足要求的三维多孔支架材料,有望应用在软骨组织工程上。     

壳聚糖/纤维素生物质发泡复合材料多孔结构的表征

以壳聚糖微粒为增强体,离子液体为纤维素溶剂,采用冷冻干燥法成功制备了壳聚糖/纤维素生物质发泡复合材料。利用SEM、XRD和TGA表征多孔复合材料微观结构、结晶性能以及热稳定性,测试了其孔隙率和吸水性能。实验结果表明:壳聚糖/纤维素多孔复合材料具有三维相互贯通的微孔结构,壳聚糖粉体有助于孔洞结构的形成,TGA结果显示纤维素多孔材料的热稳定性能得以提高。XRD结果显示纤维素经离子液体溶解再生后晶型结构由纤维素I转化为纤维素II。纤维素含量较低(≤4wt%)时,随1wt%壳聚糖粉体的加入,孔隙率明显提高。壳聚糖/纤维素多孔复合材料的力学性能随纤维素含量的增加而不断提高,而吸水性能有所下降。壳聚糖与纤维素质量比为1∶3时,壳聚糖/纤维素多孔复合材料孔隙率为72.7%,吸水率和相对保湿率分别为28.0g/g和17.6g/g,断裂强度和断裂伸长率分别为0.32 MPa和25.4%,能够作为一种优良的吸附材料用于制备高性能的医用敷料。     

Immobilisation of heparin on bacterial cellulose-chitosan nano-fibres surfaces via the cross-linking technique

In recent years, bacterial cellulose (BC) has been fabricated in tubular shape as scaffold for vascular tissue engineering. However, in order to improve the blood compatibility and regenerative ability of BC, BC nano-fibres should be cross-linked with some materials which can prevent the formation of blood clot. In this work, a novel BC-chitosan (CS)/heparin (Hep) composite was prepared. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FTIR) were used to analyse the obtained samples. It is observed by SEM and TEM that the obtained composites remain the three-dimensional (3D) network and porous structure. The results of XRD reveal that the curve of BC-CS/Hep composite assumes the characteristic absorption peaks of BC, CS and Hep. The FTIR results also confirm the presence of CS and Hep on the surface of BC nano-fibres. In conclusion, BC-CS/Hep composites were obtained by the co-synthesis technique and the cross-linking method, respectively. Furthermore, the MC3T3-E1 cells were seeded on the obtained samples to test the cell compatibility. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide results indicated that the BC-CS/Hep composites were suitable for cell proliferation and ingrowth.     

磷酸钙相组成对类骨单位复合骨支架的影响

从组成上看, 自然骨是一种无机与有机的复合材料; 从结构上看, 致密骨的基本结构单位为内壁血管化的骨单位。本研究基于组成与结构仿生的原理制备组织工程化支架, 模拟具有复杂结构的密质骨的基本单位——骨单位。为此, 通过静电纺丝和双螺杆挤出相结合的两步制造法, 制备一种具有双层结构的聚己内酯/磷酸钙(PCL/CaP)复合骨支架, 其内层是由电纺纳米纤维组成的空心管, 可贴附内皮细胞层形成与哈佛氏管相类似的结构; 其外层是具有高孔隙率的螺旋状PCL/CaP微丝, 可复合前成骨细胞以模拟骨单位结构中的外层骨样组织。为进一步探索材料组成对于支架生物功能的影响, 分别设计了外层为PCL, PCL/双相磷酸钙(PCL/BCP)和PCL/β-磷酸三钙(PCL/β-TCP)的复合支架, 比较了材料组分变化对外层微丝结构及前成骨细胞(MC3T3-E1)活性的影响。相比于PCL和PCL/β-TCP, PCL/BCP微丝更能显著增强细胞的生长和钙的沉积, 并成功获得可精确调控不同细胞的空间分布的双层复合支架, 实现对复杂结构骨单位的模拟构建, 显示出很好的应用前景。     

Fabrication and properties of porous scaffold of zein/PCL biocomposite for bone tissue engineering

The aim of this study was to fabricate porous scaffolds of zein/poly(ε-caprolactone) (PCL) biocomposite by solvent casting–particulate leaching method using sodium chloride particles as the porogen. Porous biocomposite scaffolds with porosity around 70% and well-interconnected network were obtained. The incorporation of zein into PCL led to the improvement of hydrophilicity as indicated by the results of water contact angle measurement. After immersion in phosphate buffered saline (PBS) in vitro for 28 days, it was observed that the degradation rate of the zein/PCL biocomposite scaffold was faster than the PCL scaffold and that the rate could be tailored by adjusting the amount of zein in the composite. The results demonstrate the potential of the zein/PCL biocomposite scaffolds to be used in tissue engineering strategies to regenerate bone defects.