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。     

可注射海藻酸钙水凝胶的制备研究

海藻酸钙水凝胶因其良好的生物相容性广泛应用于组织工程支架材料的研究。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可注射凝胶,用于软骨组织微创修复材料的研究。测定了单一变量条件下不同海藻酸钠浓度、f值(钙离子与羧基的摩尔比)及n值(葡萄糖酸内酯与钙离子的摩尔比)对海藻酸凝胶力学强度、溶胀率、浸提液pH值等的影响,从而获得各组分最适的配比;另外,通过原位接种软骨细胞,研究了软骨细胞在凝胶中的生长行为。综合海藻酸钙凝胶性能,最终确定海藻酸钠浓度为2.5%、f=0.5及n=0.6为最佳配比;细胞培养结果表明软骨细胞在凝胶中具有较高的活性且维持了其软骨细胞形态,证实了研究制得的海藻酸钙水凝胶是一种优良的可注射软骨组织工程支架材料。     

基于电沉积法制备图案化细胞负载型海藻酸钙水凝胶技术进展

由于海藻酸钙水凝胶具有良好的生物相容性、低毒性、低成本、并且可快速制备等优点,因此可作为生物支架材料。通过构建图案化的具有生物细胞的海藻酸钙水凝胶是生物工程中作为生物支架的重要手段之一。文中在简要介绍电沉积法制备海藻酸钙水凝胶原理的基础之上,着重阐述了近年来基于电沉积法制备图案化海藻酸钙水凝胶所提出的方法,包括电极的图案化、间接电沉积法、电沉积与3D生物打印结合、扫描电极的电沉积法以及双极电化学法,并对制备图案化细胞负载型海藻酸钙水凝胶今后发展中仍需解决的问题进行总结与展望。     

聚丙烯酸/聚乳酸复合多孔pH响应水凝胶的制备及性能

利用电纺制备直径为(2.69±0.63)μm,孔径大小为150 nm×120 nm聚乳酸(PLLA)纳米孔超细纤维。以丙烯酸(AA)为单体,N,N-亚甲基双丙烯酰胺为交联剂,过硫酸钾为引发剂,通过自由基聚合制备聚丙烯酸(PAA)水凝胶。将PLLA纳米孔超细纤维浸泡在上述体系中,通过原位聚合制备PAA/PLLA复合水凝胶,并研究m(AA)∶m(PLLA)对复合水凝胶形貌的影响。致孔剂聚乙二醇(PEG)加入,明显提高纤维孔隙率。与PAA水凝胶相比,PAA/PLLA复合水凝胶pH响应时间大大缩短,且拉伸强度由1.9 MPa增加到5.2 MPa,弹性模量从90.4 MPa增加到108.2 MPa。     

羟基磷灰石对海藻酸钙水凝胶的制备及性能的影响

采用具有良好生物相容性的羟基磷灰石(HA)作为钙源,开发了一种新型的HA-GDL交联体系制备海藻酸钙水凝胶.通过调节海藻酸钠溶液的浓度CSA和钙离子与海藻酸钠中羧基的摩尔比f,分别制备CSA=2%、2.5%、3%,f=0.27、0.36、0.54的一系列水凝胶.以CaCO3-GDL体系作为对照,系统比较了两种体系制得的水凝胶在凝胶化时间、凝胶形貌、力学性能以及溶胀收缩等方面的性能.结果显示,相同凝胶条件下,采用HA-GDL体系制得的海藻酸钙水凝胶具有较快的凝胶化速率,较为均一的凝胶结构,较强的力学性能和较低的溶胀率.将海藻酸钙凝胶与软骨细胞复合进行体外培养,结果显示该体系具有良好的细胞相容性,从而说明该材料体系可能是一种良好的软骨组织工程支架材料.     

基于电诱导沉积方法制备海藻酸钙水凝胶

海藻酸钙水凝胶是一种具有良好生物相容性、生物降解性的生物医用高分子材料,但是传统制备方法不能得到具有生理结构的水凝胶。文中提出了一种基于电诱导沉积原理,使用海藻酸钠和碳酸钙混合溶液制备海藻酸钙水凝胶的方法。在分析电诱导沉积原理基础上,搭建了海藻酸钙水凝胶3D打印系统。建立了海藻酸钙水凝胶截面宽度模型,提出了通过调节打印喷头的移动速度控制凝胶截面宽度的方法。应用该系统打印了圆管形、正六边形及四叶草形的生物支架,并用这些结构的生物支架进行细胞培养实验,获得具有一定生物活性的细胞。     

N-组氨酸壳聚糖/左旋聚乳酸支架的制备及表征

在冷冻诱导相分离制备N-组氨酸壳聚糖支架(NHCS)的基础上进行二次相分离,利用不同取代度的NHCS和不同N-组氨酸壳聚糖/聚乳酸质量比制备一系列N-组氨酸壳聚糖/聚乳酸(NHCS/PLLA)支架。通过红外光谱、广角X射线衍射、热分析和扫描电镜等来表征NHCS/PLLA支架。结果表明,同一种N-组氨酸壳聚糖支架(50kD-NHCS-3),N-组氨酸壳聚糖/聚乳酸质量比减小,支架孔隙率减小,密度增大。支架材料的孔尺寸约在12~25μm,孔隙率均大于92%,抗压强度和弹性模量分别在0.33~0.78 MPa和1.75~5.28 MPa之间,有望适用于软骨组织工程支架。     

基于电诱导沉积原理制备形状可控的海藻酸钙-多聚赖氨酸水凝胶微封装胶囊

海藻酸钙水凝胶是一种具有良好生物相容性、生物降解性的生物医用高分子材料。文中提出了一种基于电诱导沉积原理制备形状可控的海藻酸钙-多聚赖氨酸(PLL)水凝胶微封装胶囊。在涂有光刻胶的FTO导电玻璃表面上利用光刻技术制造多种预设图案的微电极,基于电诱导沉积原理在微电极上制备特定几何结构海藻酸钙水凝胶,通过PLL等试剂的处理最终得到环形与六边形结构的海藻酸钙-PLL水凝胶微封装胶囊,酵母细胞包含在微封装胶囊中进行24 h的培养,获得有一定生物活性的细胞。这种方法可以制备用于组织工程学研究的生物支架,将对细胞装配,生物打印以及药物输送等领域有重要的参考价值。     

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.     

水辅助法制备左旋聚乳酸/聚乙烯醇复合多孔膜及其力学性能

以左旋聚乳酸(PLLA)/聚乙烯醇(PVA)为成膜材料,利用水辅助法制备了PLLA/PVA复合多孔膜。研究了溶剂及其组成、环境湿度和聚合物浓度对形成多孔膜的形貌影响。筛选出可完全溶解PLLA/PVA体系的二甲亚砜(DMSO)/二氯甲烷(DCM)混合溶剂。V(DMSO)/V(DCM)=1/9为溶剂得到孔径大小为(2.45±0.31)μm的规整蜂窝孔,且随着DMSO含量增多,孔径变小,孔分布变得无序。环境湿度从43%增加到91%,孔径大小由(1.43±0.63)μm增加到(4.30±0.63)μm,孔径与环境湿度基本上呈现一阶线性关系。与纯PLLA多孔膜相比,PLLA/PVA复合多孔膜的拉伸强度和断裂伸长率分别从33.32MPa和12.46%增加到40.66MPa和32.57%。PLLA/PVA复合多孔膜有利于细胞的粘附与生长,因而有望作为组织工程支架材料。     

用于软骨和软骨下骨修复的纳米羟基磷灰石/聚乙烯醇/聚酰胺66功能梯度材料的制备和表征

利用反复冷冻-解冻法和相分离法,制备出用于软骨和软骨下骨修复的纳米羟基磷灰石(nHA)/聚乙烯醇(PVA)/聚酰胺(PA66)功能梯度材料。研究表面层PVA的力学性能和摩擦学性能,及软骨下骨nHA/PA66(m(HA)∶m(PA66)=1∶1)支架的力学性能及生物学性能。结果表明PVA拉伸强度为1.938MPa,平均摩擦系数在生理盐水及代血浆润滑条件下分别为0.076和0.085;nHA/PA66复合多孔支架孔隙率为80.93%,孔径为50～500μm,压缩强度和压缩模量分别为0.88和15.21MPa,且具有良好的生物相容性。     

氧化石墨烯增强PVA-PAA复合水凝胶的制备及性能研究

水凝胶具有高含水、低摩擦、良好生物相容性等优良性能,被认为是最具潜力的软骨修复材料,但传统水凝胶因为力学强度低限制了其应用。本实验将氧化石墨烯(GO)作为增强剂,通过冷冻-解冻与退火法相结合制备了高强度的聚乙烯醇-聚丙烯酸-氧化石墨烯(PVA-PAA-GO)复合水凝胶。结果表明:PVA-PAA-GO复合水凝胶具有多孔网状结构和良好的力学强度,随着GO含量的增加,复合水凝胶的力学强度呈先上升后下降的趋势,GO含量为0.05%时,力学强度可达34 MPa,GO含量为0.05%、1%时,PVA-PAA-GO复合水凝胶的损耗因子小于0.1,与天然软骨的动态力学性能相似。     

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/     

基于选择性激光烧结聚己内酯/蛋壳多孔支架的制备和表征

以聚己内酯(PCL)和鸡蛋壳粉末(ES)为原材料,采用选择性激光烧结技术制备纯PCL支架和PCL/ES混合材料支架。通过显微镜观察了支架形貌,测定了各组支架的孔隙率和压缩强度。结果表明ES的加入能使支架的压缩强度有所提高,但同时孔隙率稍有降低,填充速度为1380~1880 mm/min时PCL/ES支架能取得较高的孔隙率(80%)和压缩强度(8.28 MPa),达到松质骨的要求(孔隙率≥70%,压缩强度≥8.2 MPa);差示扫描量热分析和热重分析结果表明ES的加入改善了复合支架的结晶性能和热稳定性;对粉末和支架的X射线衍射和衰减全反射傅里叶变换红外光谱检测证实了ES的成分和选择性激光烧结工艺没有破坏原材料的分子官能团;用MTT比色法测定了支架毒性试验,结果表明PCL/ES复合支架无明显毒性且具有良好的生物相容性。因此,选择性激光烧结制备的PCL/ES支架具有很好的外形可塑性和空隙结构,其良好的力学性能和生物相容性使其有望在骨组织工程支架中得到应用。     

Synthesis and biocompatibility of porous nano-hydroxyapatite/collagen/alginate composite

Porous nano-hydroxyapatite/collagen/alginate (nHAC/Alginate) composite containing nHAC and Ca-crosslinked alginate is synthesized biomimetically. This composite shows a significant improvement in mechanical properties over nHAC material. Mechanical test results show that the compressive modulus and yield strength of this composite are in direct proportion to the percentage of Ca-crosslinked alginate in the composite. Primary biocompatibility experiments in vitro including fibroblasts and osteoblasts co-culture with nHAC/alginate composite indicated the high biocompatibility of this composite. Therefore the composite can be a promising candidate of scaffold material for bone tissue engineering.     

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.     

Novel crosslinked alginate/hyaluronic acid hydrogels for nerve tissue engineering

Artificial tissue engineering scaffolds can potentially provide support and guidance for the regrowth of severed axons following nerve injury. In this study, a hybrid biomaterial composed of alginate and hyaluronic acid (HA) was synthesized and characterized in terms of its suitability for covalent modification, biocompatibility for living Schwann cells and feasibility to construct three dimensional (3D) scaffolds. Carbodiimide mediated amide formation for the purpose of covalent crosslinking of the HA was carried out in the presence of calcium ions that ionically crosslink alginate. Amide formation was found to be dependent on the concentrations of carbodiimide and calcium chloride. The double-crosslinked composite hydrogels display biocompatibility that is comparable to simple HA hydrogels, allowing for Schwann cell survival and growth. No significant difference was found between composite hydrogels made from different ratios of alginate and HA. A 3D BioPlotter^TM rapid prototyping system was used to fabricate 3D scaffolds. The result indicated that combining HA with alginate facilitated the fabrication process and that 3D scaffolds with porous inner structure can be fabricated from the composite hydrogels, but not from HA alone. This information provides a basis for continuing in vitro and in vivo tests of the suitability of alginate/HA hydrogel as a biomaterial to create living cell scaffolds to support nerve regeneration.     

Compressive mechanical properties and deformation behavior of porous polymer blends of poly(ε-caprolactone) and poly(l-lactic acid)

Porous biodegradable polymeric scaffolds are developed by physically blending two different kinds of biodegradable polymers, PCL, and PLLA, for application in tissue engineering. The main objective of the development of this material is to control the mechanical properties, such as, elastic modulus and strength. The results from mechanical testing showed that the compressive mechanical properties of PCL/PLLA scaffold can be varied by changing the blend ratio. It also showed that these properties can be well predicted by the rule of mixture. The primary deformation mechanism of the scaffolds was found to be localized buckling of struts surrounding the pores. Localized ductile failure caused by PCL phase tends to be suppressed with increasing PLLA content. The immiscibility of PCL and PLLA caused the phase-separation morphology that strongly affected the macroscopic mechanical properties and the microscopic deformation behavior.     

Synthesis and characterization of porous κ-carrageenan/calcium phosphate nanocomposite scaffolds

The polysaccharide κ-carrageenan was used in the production of macroporous composites containing nanosized hydroxyapatite, with potential application in bone tissue engineering. Biodegradable composite scaffolds were prepared combining in situ co-precipitation of calcium phosphates with a freeze-drying technique. The effect of the Ca/P molar ratio and total ceramic content on the chemical composition, microstructure and mechanical performance of the scaffolds were investigated by thermal analysis, X-ray diffraction, FTIR, transmission electron microscopy, scanning electron microscopy, He porosimetry and compressive tests. A mixture of amorphous calcium phosphates and/or nanosized calcium-deficient hydroxyapatite was obtained in most of the composites. The formation of hydroxyapatite was induced by higher Ca/P ratios, probably due to competing reticulation of the biopolymer with calcium cations. The composite scaffolds presented interconnected pores (50–400 μm) and porosity around 97% and calcium phosphates were uniformly dispersed in the κ-carrageenan matrix. Both microstructure and compressive mechanical properties of the scaffolds were affected by the ceramic content and, for a Ca/P molar ratio of 1.67, maximum compressive strength was achieved for a ceramic content of ca. 25 wt%. Above this value the structural integrity of the composite was damaged and a dramatic decrease in mechanical strength was verified. Compressive mechanical properties of the composites were improved by increasing Ca/P atom ratio.