磷灰石-硅灰石/β-磷酸三钙复合多孔支架材料的制备和表征

以磷灰石-硅灰石玻璃陶瓷(AW)粉和β-磷酸三钙(β-TCP)粉为原料. 以硬脂酸为致孔剂. 经模压成型、1170℃烧结制备磷灰石-硅灰石/β-磷酸三钙复合多孔支架材料(AW/βTCP). 采用X射线衍射(XRD)、扫描电镜(SEM)、能谱(EDS)、诱导耦合等离子体原子发射光谱(ICP-AES)等方法分析支架的晶相组成、显微结构、物理性能、生物活性和降解性. 将大鼠骨髓间充质干细胞(rMSCs)与支架体外复合培养评价支架的生物相容性. 结果表明: 所制备的AW/β-TCP支架材料的抗压强度达14.3MPa. 孔隙率达66.9%. 孔径为100～700μm. 具有良好的生物相容性、生物活性和降解性. 可作为骨组织工程支架的候选材料.     

羟基丁酸与羟基辛酸共聚体骨组织工程支架的初步研究

采用粒子滤出/冷冻干燥复合法制备羟基丁酸与羟基辛酸共聚体[P(HB-HO)]多孔支架,并进行扫描电镜观察、孔隙率和力学性能检测以及体外降解和细胞相容性实验.结果表明,P(HB-HO)多孔支架孔隙分布均匀,连通性好,孔隙率为50%～90%时,抗压强度在1.7～6.2MPa之间,十二周体外降解率约为20%;与P(HB-H0)复合培养的小鼠成骨样细胞MC3T3-E1黏附率高,生长状态良好.证明P(HB-HO)具有良好的理化性能和细胞相容性,有望成为一种具有临床应用价值的骨组织工程支架材料.     

介孔生物玻璃/丝素蛋白复合多孔海绵的结构及止血性能研究

采用冷冻干燥法制备了介孔生物玻璃(M58S)/丝素蛋白(SF)复合多孔海绵,采用透射电镜(TEM)和场发射扫描电镜(FESEM)等观察M58S和复合多孔海绵的形貌和结构特征,通过体外凝血实验、大鼠肝脏止血模型和体外细胞毒性实验评价复合多孔海绵的止血性能和细胞毒性。TEM显示M58S内部具有规则的纳米级介孔孔道,排列高度有序,比表面积达400m~2/g,平均孔径为7.3nm;FESEM显示复合海绵呈现多孔沟壑状结构,孔隙率80%;APTT和PT测试结果表明该复合多孔海绵主要通过作用于血液的内源性凝血系统途径促进凝血;小鼠肝脏止血模型显示当M58S含量15%时,复合多孔海绵的止血效果较好且优于明胶海绵,有望用作体外快速止血材料。     

壳聚糖-明胶/APTES改性生物活性玻璃复合支架的制备工艺

为改善生物活性玻璃与高分子之间的相容性,利用 APTES改性生物活性玻璃(SBG),通过冷冻干燥法制备出用于骨和软骨组织工程的壳聚糖-明胶/APTES改性生物活性玻璃(CS 2Gel/ SBG)仿生型复合多孔支架,并对其孔隙率、力学性能和显微形貌进行了表征;探讨了各组分不同含量、交联剂和冷冻温度对CS-Gel/SBG复合支架孔隙率、力学性能和显微观结构的影响。研究表明,当SBG和CS-Gel的含量分别为70和40 g·L-1,用EDC和NHS交联,-50℃急冻2h后,又在-15℃ 下冷冻10h,最后真空冷冻干燥,制备出孔隙分布均匀、孔隙率达到90 %以上、三维连通的复合多孔支架。     

珍珠层粉/壳聚糖多孔支架的制备及分析测试

用负压真空冷冻干燥机在-20℃条件下冷冻干燥48h制备珍珠层粉/壳聚糖复合多孔支架。用扫描电子显微镜(SEM)观察支架表面形貌,通过X射线衍射分析(XRD)、傅里叶红外光谱(FTIR)等手段对材料进行表征测试,检测其降解性能,并将兔骨髓间充质干细胞与支架共培养检测材料细胞毒性。结果表明复合支架具有稳固的三维多孔结构,孔隙率最大至91.64%,孔径在100~300μm范围,降解性能适宜,且冷冻干燥制备方法对珍珠层粉的结构无明显破坏,并具有良好的生物相容性,有利于细胞的生长。     

多孔Nano-dHA/PLA/BCP复合支架的制备及性能研究

为改善常规的多孔聚乳酸/双相钙磷陶瓷(PLA/BCP)支架表面亲水性不佳及降解时呈酸性等不足,采用马弗炉烧结制备的BCP多孔支架浸入纳米缺钙羟基磷灰石/聚乳酸(nano-dHA/PLA)混悬液后,真空干燥得到多孔纳米缺钙羟基磷灰石/聚乳酸/双相钙磷陶瓷(nano-dHA/PLA/BCP)复合支架,利用万能测试机测试支架抗压强度,阿基米德法测定支架孔隙率,扫描电子显微镜(SEM)观察支架表面形貌,并对其保水率和体外降解过程中pH值的变化情况等进行了研究. 结果表明：多孔nano dHA/PLA/BCP复合支架表面粗糙,保水率和强度均有较大提高,在磷酸盐缓冲液（PBS）浸泡过程中pH值下降较慢,在模拟体液（SBF）中浸泡1个月后发现有较多的类骨磷灰石形成.     

负载PEO-b-PLL/DNA-TGF beta1粒子的PLGA/纤维蛋白凝胶复合支架的制备及其体外干细胞诱导分化性能

采用粒径分布在450～600μm的无规明胶颗粒为致孔剂制备乳酸-乙醇酸共聚物(PLGA)海绵体,以纤维蛋白凝胶为负载聚氧化乙烯-b-聚赖氨酸(PEO-b-PLL)/DNA粒子和骨髓间充质干细胞(BMSCs)的传递介质,通过负压将其导入PLGA多孔支架,在凝血酶和Ca2+作用下原位凝胶,构建了一种负载PEO-b-PLL/DNA粒子的PLGA/纤维蛋白凝胶/BMSCs复合支架。系统地表征了复合支架的形貌及微结构。考察了PLGA海绵体和纤维蛋白水凝胶的体外降解性能以及PEO-b-PLL/DNA粒子的体外释放行为。重点研究了BMSCs在复合支架中的形态、活性和向软骨细胞分化等生物学性能。研究结果表明:PLGA海绵体具有高孔隙率、高孔连通性;纤维蛋白凝胶均匀填充在PLGA海绵体孔隙中,而PEO-b-PLL/DNA粒子分布在纤维蛋白凝胶三维结构中;体外降解实验显示,8周后PLGA分子量为初始分子量的50%以下,而伴随着纤维蛋白凝胶的快速降解,PEO-b-PLL/DNA粒子被快速释放到溶液中;体外细胞培养结果显示,BMSCs在复合支架体系中具有良好的形态、活性和分泌软骨细胞外基质的能力。     

具有良好贯通性的颗粒造孔支架的制备及表征

支架孔隙贯通性的研究一直是多孔生物陶瓷的研究重点之一.采用石蜡球作为造孔剂, 在常规的颗粒造孔法制备多孔陶瓷支架的基础上,通过二甲苯处理以便在石蜡球间形成桥联结构, 以扩大颗粒间的接触面积,从而提高多孔陶瓷支架的孔隙贯通性. 借助扫描电镜(SEM)观察陶瓷支架的多孔结构,评价二甲苯处理石蜡球对陶瓷支架孔隙贯通性的改善效果; 采用密度法测定了陶瓷支架的孔隙率并计算其收缩率,并用成骨细胞评价陶瓷支架的细胞相容性. 结果表明,通过二甲苯的处理, 不仅改善了陶瓷支架孔隙的贯通性,而且提高了其孔隙率, 但孔隙率对陶瓷支架的收缩率无明显影响.细胞培养实验显示成骨细胞可进入多孔陶瓷支架内部, 并在材料表面正常生长,贯通性好的多孔陶瓷支架可为成骨细胞生长提供更充分的空间.     

聚(3-羟基丁酸酯-3-羟基戊酸酯)/聚碳酸亚丙酯复合支架的构建与表征

分别采用反应性和非反应性熔融共混方法结合粒子沥滤技术以及碱处理技术构建不同质量比的聚(3-羟基丁酸酯-3-羟基戊酸酯)(PHBV)/聚碳酸亚丙酯(PPC)复合支架,通过表征支架的表面形态、孔隙率大小和体外降解性能,发现反应性共混法可显著改善支架的相容性和界面粘接。非反应性熔融共混法构建的支架孔隙率高于反应性共混法构建的复合支架。随着PPC含量的升高,复合支架的孔隙率升高。当PHBV/PPC质量比达50/50时,支架在PBS缓冲液中降解最快,反应性共混法构建的支架亲水性高于非反应性共混法,碱处理技术可显著改善复合支架的亲水性。这对功能重建的体内研究和临床实践具有潜在的理论价值和应用前景。     

丝素蛋白/纳米生物玻璃复合多孔支架的结构与性能

采用冷冻干燥法制备了丝素蛋白(SF)/纳米生物玻璃(NBG)复合多孔支架材料。并用XRD、FT-IR、SEM等对SF/NBG复合支架进行了结构与性能表征。结果表明,SF/NBG复合多孔支架孔连通性较好,孔径为150～300μm,孔隙率为80.6%～90.3%;同时NBG的加入促进了复合多孔支架中SF的构象部分由无规卷曲向β-折叠转变。复合多孔支架抗压强度和抗压模量相比于纯SF多孔支架有较大提高。采用模拟体液浸泡实验研究了复合支架的体外生物活性,并用XRD、FT-IR和FESEM对试样表面进行了表征。结果显示,复合多孔支架经模拟体液浸泡7d后,表面沉积出类骨羟基磷灰石(HA)层,NBG的加入能加快复合多孔支架表面沉积类骨HA的速度。研究结果显示SF/NBG复合多孔支架材料有望作为生物活性良好的骨组织修复材料。     

Porous calcium phosphate ceramics modified with PLGA–bioactive glass

Porous calcium phosphate ceramics (mainly hydroxyapatite) with interconnected macropores (∼1 mm) and micropores (∼5 μm) as well as high porosities (∼80%) were prepared by firing polyurethane foams that were coated with calcium phosphate cement at 1200 °C. In order to improve the mechanical properties such as compressive strength and compressive modulus and maintain the desirable bioactivity (i.e. the ability of apatite layer formation), the open micropores of the struts were infiltrated with poly(lactic-co-glycolic acid) (PLGA) to achieve an interpenetrating bioactive ceramic/biodegradable polymer composite structure. The PLGA filled struts were further coated with a 58S bioactive glass (33 wt.%)–PLGA composite coating. The PLGA–bioactive glass modified porous calcium phosphate ceramics proved to be bioactive and exhibited compressive strengths up to 7.7 MPa and compressive moduli up to 3 GPa, which were comparable to those of natural spongy bones. The obtained complex porous bioactive/biodegradable composites could be used as tissue engineering scaffolds for low-load bearing applications.     

Composite scaffolds of nano calcium deficient hydroxyapatite/multi-(amino acid) copolymer for bone tissue regeneration

In this study, nano calcium deficient hydroxyapatite (n-DA)/multi-(amino acid) copolymer composite scaffolds were prepared by injection molding foaming method using calcium sulphate dihydrate as a foaming agent. The composite scaffolds showed well interconnected macropores with the pore size of ranging from 100 to 600 μm, porosity of 81 % and compressive strength of 12 MPa, and the compressive strength obviously affected by the porosity. The composite scaffolds could be slowly degraded in phosphate buffered solution (PBS), which lost its initial weight of 61 w % after immersion into PBS for 12 weeks, and the porosity significantly affected the degradability of the scaffolds. Moreover, it was found that the composite scaffolds could promote the MG-63 cells growth and proliferation, and enhance its alkaline phosphatase activity. The implantation of the scaffolds into the femoral bone of rabbits confirmed that the composite scaffolds were biocompatibitive, degradable, and osteoconductive in vivo.     

Bioresorbable and bioactive polymer/Bioglass® composites with tailored pore structure for tissue engineering applications

An overview about the development of porous bioresorbable composite materials for applications as scaffolds in tissue engineering is presented. A thermally induced phase separation method was developed to fabricate porous foam-like structures of poly(lactide-co-glycolide) (PLGA) containing bioactive glass particle additions (up to 50 wt.%) and exhibiting well-defined, oriented and interconnected porosity. The in vitro bioactivity and the degradability of the composite foams were investigated in contact with phosphate buffer saline (PBS). Weight loss, water absorption and molecular weight measurements were used to monitor the polymer degradation after incubation periods of up to 7 weeks in PBS. It was found that the presence of bioactive glass retards the polymer degradation rate for the time period investigated. The present results show a way of controlling the in vitro degradation behaviour of PLGA porous composite scaffolds by tailoring the concentration of bioactive glass.     

Fabrication of three dimensional polymeric scaffolds with spherical pores

This paper reports polymeric scaffolds with spherical internal macropores and relatively large external dimension. Paraffin spheres with the diameter of several hundred microns were prepared by a suspension technique. Particulate leaching technique based on this kind of spherical porogens was combined with room-temperature compression molding technique to fabricate biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) porous scaffolds potentially for tissue engineering or in situ tissue induction. The scaffolds exhibited ordered macropores with good pore interconnectivity. The porosity ranged from 80 to 97% adjusted simply by varying porogen content. The foams with porosity around 90% have compressive modulus over 3 MPa and compressive strength over 0.2 MPa. As preliminary cell experiments with 3T3 fibroblasts cultured on the porous scaffolds indicate, the processing procedure of the scaffolds has not brought with problem in cytotoxicity.     

复合明胶涂层对钙磷陶瓷多孔支架的增强作用

采用有机泡沫浸渍工艺制备了高孔隙率的钙磷多孔陶瓷支架, 将多孔陶瓷样品浸于明胶溶液中渗涂得到陶瓷/明胶复合支架; 采用复合明胶涂层的方法对钙磷多孔陶瓷支架进行增强处理, 在不破坏多孔支架孔隙特征的情况下, 成功地在样品的孔壁上复合了明胶涂层。复合明胶涂层提高了样品的压缩强度和压缩模量, 与未涂覆样品相比, 涂敷样品受压时的应变特性发生了明显变化。尤其是渗涂5%明胶溶液的多孔样品, 在保持高孔隙率(82.8%)的条件下其压缩强度和压缩模量分别由原来的1.04MPa 和 0.105GPa增加到5.17MPa和0.325GPa。研究结果表明, 孔壁上复合明胶涂层可以有效地增强多孔陶瓷支架。      

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.     

Porous poly (lactic-co-glycolide) microsphere sintered scaffolds for tissue repair applications

In this paper, a new route to preparing porous poly (lactic-co-glycolide) (PLGA) scaffolds for bone tissue repair applications was developed. Novel porous PLGA scaffolds were fabricated via microsphere sintered technique and gas forming technique. Ammonium bicarbonate was used to regulate porosity of these porous scaffolds. Porosity of the scaffolds, and cell attachment, viability and proliferation on the scaffolds were evaluated. The results indicated that PLGA porous scaffolds were with the porosity from around 30% to 95% by regulating ammonium bicarbonate content from 0 to 10%. We also found that PLGA porous microsphere scaffolds benefited cell attachment and viability. Taken together, the achieved porous scaffolds have controlled porosity and also support mesenchymal stem cell proliferation, which could serve as potential scaffolds for bone repair applications.     

Fabrication and cell affinity of biomimetic structured PLGA/articular cartilage ECM composite scaffold

An ideal scaffold for cartilage tissue engineering should be biomimetic in not only mechanical property and biochemical composition, but also the morphological structure. In this research, we fabricated a composite scaffold with oriented structure to mimic cartilage physiological morphology, where natural nanofibrous articular cartilage extracellular matrix (ACECM) was used to mimic the biochemical composition, and synthetic PLGA was used to enhance the mechanical strength of ACECM. The composite scaffold has well oriented structure and more than 89% of porosity as well as about 107 μm of average pore diameter. The composite scaffold was compared with ACECM and PLGA scaffolds. Cell proliferation test showed that the number of MSCs in ACECM and composite scaffolds was noticeably bigger than that in PLGA scaffold, which was coincident with results of SEM observation and cell viability staining. The water absorption of ACECM and composite scaffolds were 22.1 and 10.2 times respectively, which was much higher than that of PLGA scaffolds (3.8 times). The compressive modulus of composite scaffold in hydrous status was 1.03 MPa, which was near 10 times higher than that of hydrous ACECM scaffold. The aforementioned results suggested that the composite scaffold has the potential for application in cartilage tissue engineering.     

Preparation of poly(3-hydroxybutyrate)/nano-hydroxyapatite composite scaffolds for bone tissue engineering

Poly(3-hydroxybutyrate)/nano-hydroxyapatite (PHB/nHA) composite scaffolds were fabricated via powder mixing, compression moulding, and particle leaching technique. The scaffolds had high porosity with interconnected porous architecture, a favorable structure for cell attachment and new bone tissue ingrowth. A homogeneous dispersion and a uniform distribution of HA nanoparticles in the polymer matrix were obtained. The scaffolds exhibited improved compressive modulus and compressive strength, which were all in the range of compressive modulus and compressive strength of cancellous bone. In addition, the use of toxic organic solvents was eliminated. Thus, the fabricated PHB/nHA composite scaffolds tend to be promising for application in bone tissue engineering.