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.     

聚乳酸/聚乙二醇/羟基磷灰石多孔骨支架的3D打印制备及其生物相容性

聚乳酸(PLA)是一种应用广泛的生物高分子材料,但在应用过程中存在韧性、亲水性、生物活性差等缺点。用聚乙二醇(PEG)和羟基磷灰石(HA)对PLA进行改性。通过熔融共混制备不同质量比的PLA/PEG/HA复合3D打印线材,并通过分析PLA/PEG/HA线材的力学性能、结晶性能、热性能、流变性能等,筛选更适合熔融沉积成型(FDM)的3D打印成型线材,进而利用3D打印制备精度高的力学性能试样及生物相容性好、细胞可增殖和分化的生物多孔支架。结果表明:PEG的添加提高了PLA的韧性,降低了PLA的熔点。HA的添加则提高PLA/PEG/HA复合材料的弹性模量和冷结晶温度,同时HA也可以改善复合材料的加工性能。SEM与荧光标记结果表明多孔支架与细胞具有良好的生物相容性。生物支架对体外细胞的成功培养,为进一步发掘生物多孔支架在动物体内、生物医学及定制化应用方面提供了潜在可能。     

羟基磷灰石聚乳酸多孔复合材料的制备与表征

羟基磷灰石陶瓷(HA)与人体具有良好的生物相容性,能够与骨结合,可用于骨代替材料,但其机械性能欠佳,还有待提高。聚乳酸(PLA)具有良好的生物相容性和降解性能。现将二者复合制备了HA/PLA复合物,采用超声分散法制备不同比例的HA/PLA多孔复合材料,并对该材料进行了相关的表征。结果表明HA/PLA比例在70:100时获得孔隙率及综合性能较好的多孔材料。     

生物医用聚乳酸材料的改性研究进展

聚乳酸(PLA)是一种具有良好生物相容性的生物医用可降解材料,介绍了近几年来,为提高PLA性能对其进行化学改性、物理改性的研究进展,并展望了PLA改性的研究方向。     

PLA-PEG-PLA/PLA组织工程支架在模拟体液中的降解和生物矿化性能

系统研究了含有聚乳酸-聚乙二醇-聚乳酸嵌段共聚物(PLA-PEG-PLA)的聚乳酸组织工程支架在模拟体液(SBF)中的降解和生物矿化性能。通过研究可以得到如下结论:随着含有PLA-PEG-PLA共聚物的聚乳酸组织工程支架在模拟体液中浸泡时间的增长,模拟体液的pH值有下降趋势;支架材料的质量有升有降,是降解和矿化作用共同影响的结果。X射线衍射图谱和FT-IR漫反射图谱研究表明,浸在SBF中的支架表面有磷灰石沉积物出现,并且PLA-PEG-PLA共聚物降解速度比PLA快。     

超临界CO2反复循环萃取法制备PLA/TCP多孔组织工程支架材料

相对于传统的超临界CO2（SC—CO2）一次性升压法，采用SC—CO2反复循环萃取法制备了聚乳酸（PLA）／磷酸三钙（TCP）复合多孔支架材料，以提高材料的孔洞连通率。本文研究了材料的开孔率，不同PLA和TCP配比材料的孔洞形态以及材料的力学性能。结果表明，反复循环萃取法制备的材料比传统的一次性升压法制备的材料的开孔率可以提高10%左右，孔径在200-300μm之间，孔壁上有丝网型等几种适合细胞种植的特殊微隙形态；TCP在PLA支架中的分散性很好；材料压缩模量和压缩强度分别可达71.8和7．1MPa，比单纯的PLA材料明显增加。     

用超临界CO2法制备聚乳酸三维多孔支架材料

在超临界CO2(SC—CO2)条件下制备了生物相容性良好的聚乳酸(PLA)多孔材料，研究了PLA的分子量、SC—CO2的压力、温度和处理时间对多孔材料的结构形态、孔隙率和玻璃化温度的影响。结果表明：支架材料的孔洞分布、结构形态和孔隙率不仅与聚乳酸的分子量有关，而且与处理样品的压力、温度和时间关系密切；经超临界CO2处理后材料的玻璃化温度(Tg)有所升高，与传统的方法所制得的材料相比较，多孔材料不仅杂质少，孔径孔率分布均匀，孔洞表面粗糙，而且在大孔之间几乎布满了直径为10—20μm的微孔，该结构提供了营养物质和新陈代谢的通道，且细胞和生长因子也能通过。     

几种聚乳酸／生物活性陶瓷复合材料生物活性的比较

采用溶解共混法制备含30％硅灰石的聚乳酸／硅灰石新型生物医用复合物膜．将其放入37．5℃模拟体液中,分别在1,3和6d取出样品,从沉积物形成速度以及沉积物的量考察复合物的生物活性,并与目前研究应用较多的聚乳酸／羟基磷灰石、聚乳酸／磷酸三钙以及聚乳酸／珍珠层粉进行比较。扫描电镜和红外光谱分析表明,聚乳酸／硅灰石、聚乳酸／羟基磷灰石和聚乳酸／磷酸三钙复合物膜的生物活性明显优于聚乳酸／珍珠层粉,这三种复合物膜表面在浸泡一天时表面出现类骨羟基磷灰石沉积物,6d时表面完全被沉积物覆盖。聚乳酸／硅灰石复合物材料具有较好的生物活性,适于应用在骨修复以及骨组织工程领域。     

多孔磷酸钙骨水泥组织工程支架的高分子灌注增强

利用棒状谷氨酸钠晶体作为造孔粒子,采用可溶盐造孔法,制备了三维连通的大孔径多孔磷酸钙骨水泥支架,分别将明胶(Gelatin) 、聚乳酸2羟基乙酸共聚物(PLGA) 、聚乳酸(PLA) 、聚己内酯(PCL) 、聚羟基丁酸戊酸酯(PHBV)灌注到多孔磷酸钙骨水泥(CPC)支架的孔隙中以改善支架材料的力学性能。结果表明,5 种高分子材料与水的接触角大小顺序为PHBV > PCL > PLA > PL GA > Gelatin , 复合支架材料的强度随高分子材料与水接触角的减小而增大;除PHBV外,其余4种均有明显的增强效果,其中Gelatin/CPC复合支架增强效果最好,强度达到2. 25 MPa±0. 02 MPa ,是CPC支架强度的25倍。经过增强的大孔径多孔磷酸钙骨水泥复合支架可用作骨组织工程支架材料。      

不同材料包裹的肝素缓释微囊生物相容性评价

制备了三种包覆材料不同的肝素微胶囊，研究了它们的缓释速度。然后把三种肝素微量与聚乳酸制成复合材料，研究其生物相容性，结果表明，胶囊中壳聚糖的加入使微量的释放速度变慢。三种微囊与PLA的复合材料经皮肤刺激试验、皮内刺激试验、热原试验、全身急性毒性试验和细胞培养试验，结果表明，所制备的复合材料在生物学评价试验中均星阴性反应，材料无明显毒性，材料中不存在潜在致敏性物质，所合热原含量符合生物体的要求。肝素缓释微胶囊／PLA复合材料符合三维多孔材料的要求，又具有优良的生物相容性。     

生物活性玻璃/PLA-PEG-PLA/聚乳酸组织工程支架在SBF溶液中的降解和矿化

通过测定pH值、质量损失率、SEM、XRD和FTIR,系统研究了生物活性玻璃/聚乳酸-聚乙二醇-聚乳酸嵌段共聚物（PLA-PEG-PLA）/聚乳酸组织工程支架在模拟体液（SBF）中的降解和生物矿化性能。研究结果表明：随着支架在SBF溶液中浸泡时间的延长,SBF的pH值和支架的质量呈下降趋势;生物活性玻璃的存在使pH值升高,而PLA-PEG-PLA嵌段共聚物的存在使pH值降低。XRD、FTIR图谱和SEM图像表明：在SBF中浸泡一定时间后,有无定型或结晶不完善的磷灰石在生物活性玻璃/PLA-PEG-PLA/聚乳酸组织工程支架表面沉积形成,并且PLA-PEG-PLA共聚物降解速度比聚乳酸快;在SBF中浸泡7天后,PLA-PEG-PLA共聚物的含量已经很难通过FTIR检测出来。     

Electrospun PCL/PLA/HA based nanofibers as scaffold for osteoblast-like cells

Polycaprolactone (PCL), poly (lactic acid) (PLA) and hydroxyapatite (HA) are frequently used as materials for tissue engineering. In this study, PCL/PLA/HA nanofiber mats with different weight ratio were prepared using electrospinning. Their structure and morphology were studied by FTIR and FESEM. FTIR results demonstrated that the HA particles were successfully incorporated into the PCL/PLA nanofibers. The FESEM images showed that the surface of fibers became coarser with the introduction of HA nanoparticles into PCL/PLA system. Furthermore, the addition of HA led to the decreasing of fiber diameter. The average diameters of PCL/PLA/HA nanofiber were in the range of 300-600 nm, while that of PCL/PLA was 776 +/- 15.4 nm. The effect of nanofiber composition on the osteoblast-like MC3T3-E1 cell adhesion and proliferation were investigated as the preliminary biological evaluation of the scaffold. The MC3T3-E1 cell could be attached actively on all the scaffolds. The MTT assay revealed that PCL/PLA/HA scaffold shows significantly higher cell proliferation than PCL/PLA scaffolds. After 15 days of culture, mineral particles on the surface of the cells was appeared on PCL/PLA/HA nanofibers while normal cell spreading morphology on PCL/PLA nanofibers. These results manifested that electrospun PCL/PLA/HA scaffolds could enhance bone regeneration, showing their marvelous prospect as scaffolds for bone tissue engineering.     

Providing osteogenesis conditions to mesenchymal stem cells using bioactive nanocomposite bone scaffolds

Development of bone scaffolds with excellent osteogenic potential is highly important for stem cell-based bone engineering. Here we developed novel scaffolds made of poly(lactic acid) (PLA) biopolymer with bioactive glass nanocomponent. In vitro bone bioactivity and osteogenic potential of the nanocomposite scaffolds were determined using bone marrow mesenchymal stem cells. Glass nanocomponent was evenly embedded within the PLA matrix while preserving the scaffold pore structure. Simulated body fluid (SBF) test revealed rapid induction of bone mineral-like apatite over the surface of the nanocomposite scaffold, which was not readily observed in the PLA. Cells adhered well onto the nanocomposite scaffold and multiplied during culture period. Nanocomposite scaffold significantly stimulated alkaline phosphatase (ALP) activity and the expression of bone-associated genes (collagen I, ALP, osteopontin and osteocalcin) with respect to PLA. Western blot analysis confirmed the osteogenic protein level was also higher on the nanocomposite scaffold. Results suggest that the nanocomposite scaffolds provide favorable conditions for osteogenesis of MSCs and thus find potential uses in bone tissue engineering.     

Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue engineering scaffolds fabricated by microcellular injection molding

Polylactic acid (PLA) and thermoplastic polyurethane (TPU) are two kinds of biocompatible and biodegradable polymers that can be used in biomedical applications. PLA has rigid mechanical properties while TPU possesses flexible mechanical properties. Blended TPU/PLA tissue engineering scaffolds at different ratios for tunable properties were fabricated via twin screw extrusion and microcellular injection molding techniques for the first time. Multiple test methods were used to characterize these materials. Fourier transform infrared spectroscopy (FTIR) confirmed the existence of the two components in the blends; differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirmed the immiscibility between the TPU and PLA. Scanning electron microscopy (SEM) images verified that, at the composition ratios studied, PLA was dispersed as spheres or islands inside the TPU matrix and that this phase morphology further influenced the scaffold's microstructure and surface roughness. The blends exhibited a large range of mechanical properties that covered several human tissue requirements. 3T3 fibroblast cell culture showed that the scaffolds supported cell proliferation and migration properly. Most importantly, this study demonstrated the feasibility of mass producing biocompatible PLA/TPU scaffolds with tunable microstructures, surface roughnesses, and mechanical properties that have the potential to be used as artificial scaffolds in multiple tissue engineering applications.     

β-磷酸三钙/聚乳酸组织工程支架在模拟体液中的降解和矿化性能

利用扫描电镜、X射线衍射仪、红外漫反射仪,以及对β-磷酸三钙/聚乳酸组织工程支架在模拟体液(SBF)中失重率和模拟体液pH值的变化的测试,系统研究了聚乳酸组织工程支架在模拟体液中的降解和矿化性能。结果发现,随着β-磷酸三钙/聚乳酸组织工程支架在模拟体液中浸泡时间的增长,模拟体液的pH值有下降趋势;支架材料的质量是降解和矿化作用共同影响的结果。X射线衍射图谱和红外光谱(FT-IR)漫反射图谱研究表明,浸在SBF中的支架表面有磷灰石沉积物出现,且沉积物与β-磷酸三钙的晶型相似。     

Fabrication of mineralized electrospun PLGA and PLGA/gelatin nanofibers and their potential in bone tissue engineering

Surface mineralization is an effective method to produce calcium phosphate apatite coating on the surface of bone tissue scaffold which could create an osteophilic environment similar to the natural extracellular matrix for bone cells. In this study, we prepared mineralized poly(d,l-lactide-co-glycolide) (PLGA) and PLGA/gelatin electrospun nanofibers via depositing calcium phosphate apatite coating on the surface of these nanofibers to fabricate bone tissue engineering scaffolds by concentrated simulated body fluid method, supersaturated calcification solution method and alternate soaking method. The apatite products were characterized by the scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), and X-ray diffractometry (XRD) methods. A large amount of calcium phosphate apatite composed of dicalcium phosphate dihydrate (DCPD), hydroxyapatite (HA) and octacalcium phosphate (OCP) was deposited on the surface of resulting nanofibers in short times via three mineralizing methods. A larger amount of calcium phosphate was deposited on the surface of PLGA/gelatin nanofibers rather than PLGA nanofibers because gelatin acted as nucleation center for the formation of calcium phosphate. The cell culture experiments revealed that the difference of morphology and components of calcium phosphate apatite did not show much influence on the cell adhesion, proliferation and activity.     

Fabrication of fibrous poly(butylene succinate)/wollastonite/apatite composite scaffolds by electrospinning and biomimetic process

In this paper, a novel kind of Poly(butylene succinate) (PBSU) /wollastonite/apatite composite scaffold was fabricated via electrospinning and biomimetic process. Pure PBSU scaffold and composite scaffolds with 12.5 wt% and 25 wt% wollastonite were firstly fabricated by electrospinning. SEM micrographs showed that all the electrospun scaffolds had homogeneous fibrous structures with interconnected pores and randomly oriented ultrafine fibers. The composite scaffolds were then surface modified using a biomimetic process. SEM and XRD results showed that apatite could deposit on the surfaces of the composite fibers after incubation in SBF and a novel fibrous structure with microspheres composed of worm-like apatite on composite fibers was formed. Incubation time and wollastonite content were found to influence the morphology of the scaffolds during the biomimetic process obviously. Both the amount and the size of the microspheres on the composite scaffolds increased with increased incubation time. After a certain incubation time, microspheres formed on the composite fibers with less wollastonite had a relatively larger size. Therefore, the microstructure of the composite scaffolds could be adjusted by controlling the wollastonite content and the incubation time. All of these results suggest that it is an effective approach to fabricate PBSU/wollastonite/apatite fibrous composite scaffolds with different material content and controllable microstructure for bone tissue engineering.     

In vitro degradation of porous poly(lactic acid)/quantum dots scaffolds

In this study, cadmium selenide/zinc sulfide (CdSe/ZnS) quantum dots (QDs) were introduced into poly(lactic acid) (PLA) for fabrication of photoluminescent PLA/QDs scaffolds. TEM images revealed that the QDs were uniformly dispersed in the PLA. Compressive modulus and thermal stability of the PLA/QDs scaffolds are higher than those of the unfilled PLA scaffold. Cytotoxicity test results confirmed the non-cytotoxicity of the PLA/QDs scaffolds. During the process of in vitro degradation, the degradation rate of the PLA was accelerated by the presence of the QDs, and the molecular weight distributions of the PLA/QDs scaffolds were much broader when compared with the unfilled PLA ones. During the first 84 weeks of the degradation process, the photoluminescence (PL) intensity of the PLA/QDs scaffolds decreased with almost the same degradation ratio. The results suggested that the CdSe/ZnS QDs have potential applications for monitoring in vivo degradation of tissue engineering scaffolds.     

Biodegradable poly(lactic acid)/hydroxyl apatite 3D porous scaffolds using high-pressure molding and salt leaching

Scaffolds comprising poly(lactic acid) (PLA) and hydroxyl apatite (HA) were fabricated by combination of the high-pressure compression-molding plus salt-leaching techniques. The optimized HA content was determined in terms of the pore morphology, porosity, storage modulus, degradation behavior, hydrophilicity as well as the cell growth ability of the scaffolds. At HA content of 20 wt%, the scaffolds exhibited an interconnected open pore structure with the high porosity of 82.2 %. More importantly, the storage modulus of PLA/HA scaffolds (87.6 MPa) achieved almost three times higher compared with pure PLA scaffolds, while under low-pressure condition, the increase of modulus caused by HA does not reach 150 %. The obvious contrast indicated that HA and high pressure had a synergistic effect on enhancing mechanical properties of porous scaffolds. It was truly interesting that the hydrophilicity of PLA/HA scaffolds was significantly improved by alkaline hydrolysis treatment, which eventually led to the excellent cellular biocompatibility of the scaffolds, as revealed from the morphology and spreading of the cells cultured in our scaffolds. On the whole, the resultant PLA/HA scaffolds are well-suited candidates for the design of tailor-made matrices in tissue engineering.