海藻酸钙水凝胶/聚乳酸复合材料的制备与性能

通过化学发泡-冷冻干燥-粒子滤出复合法制备聚乳酸(PLLA)大孔支架, 然后在大孔内以海藻酸钠(SA)、碳酸钙、葡萄糖酸内酯(GDL)为原料, 通过原位相转变制备海藻酸钙水凝胶/聚乳酸复合材料(CA/PLLA); 分别利用SEM、压缩强度测试和细胞培养对CA/PLLA支架的形貌、力学性能及生物相容性进行了研究。结果表明: PLLA具有直径小于2 mm、孔道相互连通的孔洞, 且在大孔中能够形成均匀的CA。CA/PLLA复合材料的压缩强度(2.74 MPa)远大于单一的海藻酸钙水凝胶的压缩强度(0.10 MPa)。在CA/PLLA复合支架中, 软骨细胞呈簇状圆形生长状态, 与其在天然软骨陷窝里生长状态一致。这种软硬结合、天然与合成高分子杂化的CA/PLLA复合材料的力学强度和生物相容性同时得到提高, 可进一步作为骨和软骨修复材料研究。     

β-磷酸三钙/聚L-乳酸与大鼠骨膜成骨细胞复合骨修复材料的研究

采用溶液浇铸-模压成型-沥滤方法制备了β-TCP/PLLA多孔支架材料, 将支架材料与大鼠骨膜成骨细胞复合获得新型组织工程骨修复材料. 通过抗压强度及压缩模量的表征研究了支架材料的力学性能; 采用SEM观测、MTT法、碱性磷酸酶活性及骨钙素分泌量检测细胞复合材料的体外成骨特性; 通过裸鼠肌袋种植, 以组织学方法评价细胞复合材料的异位成骨能力. 结果表明: β-TCP/PLLA多孔支架材料孔隙率可调, 孔径为100～00μm, 孔道相互贯通; 材料抗压强度和压缩模量随孔隙率的增大而降低, β-TCP复合PLLA后材料的力学性能高于同孔隙率的纯PLLA多孔材料; 复合支架材料适宜骨膜成骨细胞粘附和生长, 无细胞毒性; 骨膜成骨细胞复合β-TCP/PLLA支架材料的体外成骨特性良好, 且具有体内异位成骨能力.     

碳酸氢氨制孔制备聚乳酸(PLLA)/β磷酸三钙(β-TCP)复合骨修复多孔支架材料

采用混合溶剂(氯仿,丙酮)溶解后的聚乳酸(PLLA)与β磷酸三钙(β-TCP)、制孔剂碳酸氢氨(NH4HCO3)复合,冷冻干燥成型制备聚乳酸/β磷酸三钙多孔复合支架材料.正交实验结果表明,适当比例的混合溶剂在-10℃间体积收缩干燥制备的材料具有良好的成型性能和力学强度,碳酸氢氨(粒径200～400μm)质量比为30%(wt),PLLA/β-TCP质量比为1:1时,制备的支架材料抗压强度5.6MPa,孔隙率66.3%,孔径200～400μm.得到理想的复合骨修复多孔支架材料.     

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。      

介孔纳米羟基磷灰石/左旋聚乳酸复合材料的制备及性能

为考察介孔纳米羟基磷灰石(MHA)/左旋聚乳酸(PLLA)复合材料的性能,以十六烷基三甲基溴化铵(CTAB)为模板合成MHA,采用溶液相分离结合粒子沥滤法制备了不同纳米粒子含量的MHA/PLLA多孔支架复合材料,考察了其抗压缩性能和淬断面微观结构。采用溶液浇注法制备了MHA/PLLA复合膜,并对其拉伸性能和拉伸断面微观结构进行了研究。FTIR、XRD、TEM和氮气吸附测试等结果显示:合成的MHA具有典型的晶体结构、介孔结构和较高的比表面积。力学测试结果显示:在发生10%压缩形变时,填料含量为1%、5%和10%的MHA/PLLA多孔支架复合材料的抗压缩强度随填料含量增加而提高,与相应含量的纳米羟基磷灰石(HA)/PLLA多孔支架复合材料相比,分别提高了约37.0%、67.7%和144.7%。在填料含量为5%和10%时,MHA/PLLA复合膜的拉伸强度较HA/PLLA复合膜分别提高约38.7%和46.1%,拉伸模量分别提高约35.4%和14.5%。而且MHA/PLLA复合膜具有更高的断裂伸长率,填料含量为1%、5%和10%时断裂伸长率分别较HA/PLLA复合膜提高约91.3%、79.7%和96.1%。FESEM结果显示:尤其当填料含量较高时,MHA/PLLA多孔支架复合材料或复合膜中填料粒子分布较HA/PLLA中均匀。结果表明:与HA/PLLA复合材料相比,随着MHA含量增加,MHA/PLLA复合材料具有更好的力学性能,MHA在PLLA基体中分布相对更均匀。     

聚L-乳酸/β-磷酸三钙复合骨支架材料成型工艺优化研究

利用溶剂自扩散-模压成型-粒子沥滤法制备聚L-乳酸(PLLA)/β-磷酸三钙(β-TCP)复合多孔支架材料,采用正交设计对成型工艺进行了优化,对支架进行了形貌观察、力学强度和孔隙率大小测试.结果表明:当PLLA∶β-TCP=1∶2,成型压力5 MPa,致孔剂粒径125～400 μm,用量80%(wt)时,制备的支架材料孔结构三维贯通,抗压强度为4.45 MPa、孔隙率为60.7%,满足骨组织工程支架材料要求.     

分级多孔结构聚乳酸支架的制备与性能研究

以左旋聚乳酸为原料,1,4-二氧六环/水为溶剂,采用热致相分离法制备了具有分级多孔结构的组织工程支架。研究了溶剂配比、粗化时间对支架结构和性能的影响。溶剂比为87/13(1,4-二氧六环/水),PLLA浓度5%,粗化1h时,制备出大孔孔径达300μm,小孔嵌在大孔孔壁上且孔径在10μm以下的高连通分级多孔支架。粗化时间的延长使大孔孔径有所增大。细胞实验表明分级多孔支架有助于细胞长入支架内部,促进细胞的增殖。     

聚L-乳酸/β-磷酸三钙复合骨支架材料成型工艺优化研究

利用溶剂自扩散-模压成型-粒子沥滤法制备聚L-乳酸(PLLA)/β-磷酸三钙(β-TCP)复合多孔支架材料,采用正交设计对成型工艺进行了优化,对支架进行了形貌观察、力学强度和孔隙率大小测试。结果表明:当PLLA:β-TCP=1:2,成型压力5MPa,致孔剂粒径125～400μm,用量80% (wt)时,制备的支架材料孔结构三维贯通,抗压强度为4．45MPa、孔隙率为60．7%,满足骨组织工程支架材料要求。     

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。     

纳米复合支架结构与生物学性能

通过复合成型致孔一体技术制备纳米羟基磷灰石/聚酰胺66 (n-HA/PA66) 硬组织修复支架,采用SEM、XRD、IR和燃烧实验等测试手段对复合支架进行表征。结果表明:n-HA粒子以纳米尺度均匀分布于复合支架材料中;复合材料的两相界面为氢键键合和配位键合;支架的孔隙相互贯通,不仅有平均孔径约450 μ m的大孔,大孔壁上还富含0.5~50 μ m的微孔。动物实验证实,该纳米复合支架具有高的生物活性和好的组织相容性,能与硬组织形成骨性结合,其孔隙范围有利于骨组织、血管、骨细胞的长入,可作为硬组织修复的良好载体。      

In Vitro Characterizations of PLLA/β-TCP Porous Matrix Materials and RMSC-PLLA-β-TCP Composite Scaffolds

To develop a novel degradable poly (L-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) bioactive materials for bone tissueengineering, β-TCP powder was produced by a new wet process. Porous scaffolds were prepared by three steps, i.e. solventcasting, compression molding and leaching stage. Factors influencing the compressive strength and the degradation behaviorof the porous scaffold, e.g. weight fraction of pore forming agent-sodium chloride (NaCl), weight ratio of PLLA: β-TCP,the particle size of β-TCP and the porosity, were discussed in details. Rat marrow stromal cells (RMSC) were incorporatedinto the composite by tissue engineering approach. Biological and osteogenesis potential of the composite scaffold weredetermined with MTT assay, alkaline phosphatase (ALP) activity and bone osteocalcin (OCN) content evaluation. Resultsshow that PLLA/β-TCP bioactive porous scaffold has good mechanical and pore structure with adjustable compressive strengthneeded for surgery. RMSCs seeding on porous PLLA/     

Preparation and characterization of dense nanohydroxyapatite/PLLA composites

Synthetic bone graft substitutes based on PLLA have been largely studied during the past decade. PLLA/hydroxyapatite composites appear as promising materials for large bone defect healing. In this study dense PLLA/nano-hydroxyapatite composites were prepared by hot pressing. Dense samples were investigated rather than porous scaffolds, in order to shed light on possible correlations between intrinsic mechanical properties and nano-hydroxyapatite concentration. Hydroxyapatite deagglomerated by wet attrition milling, and further dispersed into chloroform was used (median diameter = 80 nm). Particle size distribution measurements and transmission electron microscopy show evidence that particle size and dispersion are maintained throughout the successive steps of composite processing. Mechanical properties were tested (uni-axial and diametral compression tests) as a function of nano-hydroxyapatite content. Increasing concentrations of nano-hydroxyapatite (0, 25 and 50 wt.%) increase the Young's modulus and the mechanical strength of the composite; at the same time, the failure mechanism of the material changes from plastic to brittle. Young's modulus over 6 GPa and uniaxial compressive strength over 100 MPa have been achieved. These values expressed in terms of intrinsic tensile and shear strengths indicate that 50 wt.% nano-hydroxyapatite containing samples develop properties comparable to those of cortical bone. PLLA/nano-hydroxyapatite composites are thus promising candidates to develop bioresorbable porous bone substitutes showing superior mechanical performance.     

Sol-gel原位相转变矿化制备纳米羟基磷灰石/壳聚糖复合支架材料

为了模拟天然骨组织的结构和成分, 以羟基磷灰石(HA)为钙磷源, 以壳聚糖(CS)为大分子基质材料, 在酸性环境中形成均相溶液, 通过Sol-gel相转变矿化方法和陈化处理, 原位构建了纳米HA/CS复合多孔支架材料, 研究了共沉积时体系的pH值和陈化时间对支架压缩强度、晶相组成及形貌等的影响。结果表明体系pH为10和11时, 支架的力学强度远高于未矿化壳聚糖支架强度, 但是随着体系pH的升高强度逐渐下降。XRD分析结果表明陈化处理有利于磷酸钙盐向HA转化, 随着陈化时间的延长, 纳米HA沿c轴择优生长。SEM观察显示支架材料具有相互贯穿的多孔结构, 纳米级的短棒状或颗粒状HA晶体颗粒均匀分散在孔壁上, 随着陈化处理以及陈化时间的延长, 形成致密的纳米无机/有机均匀复合体。这种快速深度矿化方法为骨支架材料的制备提供了新思路。      

Fabrication and mechanical properties of PLLA/PCL/HA composites via a biomimetic, dip coating, and hot compression procedure

Currently, the bone-repair biomaterials market is dominated by high modulus metals and their alloys. The problem of stress-shielding, which results from elastic modulus mismatch between these metallic materials and natural bone, has stimulated increasing research into the development of polymer-ceramic composite materials that can more closely match the modulus of bone. In this study, we prepared poly(l-lactic acid)/hydroxyapatite/poly(ε-caprolactone) (PLLA/HA/PCL) composites via a four-step process, which includes surface etching of the fiber, the deposition of the HA coating onto the PLLA fibers through immersion in simulated body fluid (SBF), PCL coating through a dip-coating process, and hot compression molding. The initial HA-coated PLLA fiber had a homogeneous and continuous coating with a gradient structure. The effects of HA: PCL ratio and molding temperature on flexural mechanical properties were studied and both were shown to be important to mechanical properties. Mechanical results showed that at low molding temperatures and up to an HA: PCL volume ratio of 1, the flexural strain decreased while the flexural modulus and strength increased. At higher mold temperatures with a lower viscosity of the PCL a HA: PCL ratio of 1.6 gave similar properties. The process successfully produced composites with flexural moduli near the lower range of bone. Such composites may have clinical use for load bearing bone fixation.     

Needle-like nano hydroxyapatite/poly(l-lactide acid) composite scaffold for bone tissue engineering application

In this paper, a new nano-hydroxyapatite / poly (l-lactide acid) (nHAP/PLLA) composite scaffold comprising needle-like nHAP particles was prepared. In the first step, the identification and morphology of chemically synthesized HAP particles were determined by XRD, EDX, FTIR and SEM analyses. The needle-like nHAP particles with an average size of approximately 30–60 nm in width and 100–400 nm in length were found similar to needle-like bone nano apatites in terms of chemical composition and morphology. In the second step, nHAP and micro-sized HAP (mHAP) particles were used to fabricate HAP filled PLLA (HAP/PLLA) composites scaffolds using solid–liquid phase separation method. The porosity of scaffolds was up to 85%, and their average macropore diameter was in the range of 64–175 µm. FTIR and XRD analyses showed the presence of molecular interactions and chemical linkages between HAP particles and PLLA matrix. The compressive strength of nanocomposite scaffolds could high up to 8.46 MPa while those of pure PLLA and microcomposite scaffolds were 1.79 and 4.61 MPa, respectively. The cell affinity and cytocompatibility of the nanocomposite scaffold were found to be higher than those of pure PLLA and microcomposite scaffolds. Based on the results, the newly developed nHAP/PLLA composite scaffold is comparable with cancellous bone in terms of microstructure and mechanical strength, so it may be a suitable alternative for bone tissue engineering applications.     

骨组织工程用硅胶/掺锶β-磷酸三钙/硫酸钙复合多孔支架的制备与性能研究

以掺锶β-磷酸三钙/硫酸钙为原料,利用搅拌喷雾干燥法制备出掺锶β-磷酸三钙/硫酸钙复合小球,再将硅胶与制备的复合小球复合,通过在模具中堆垛聚集的方法,制备出硅胶/掺锶β-磷酸三钙/硫酸钙复合生物支架。采用XRD,SEM,FT-IR等方法分析制得复合多孔支架的成分、形貌以及结构特征,并研究复合生物支架的降解性、孔隙率、力学性能和细胞毒性等。结果表明:该复合多孔生物支架具有一定的不规则孔洞结构,小球与小球之间的孔隙约为0.2~1mm,而每个小球上也有大量的微孔,孔径在50~200μm之间,且平均孔隙率达到62%,基本能满足骨组织工程支架对孔隙率的要求;该复合多孔支架无细胞毒性,其降解周期约为80天,抗压强度约为0.1MPa,因此该支架在非承重骨组织修复方面具有良好的应用前景。     

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.