On Modeling Bio-Scaffolds:Structural and Fluid Transport Characterization Based on 3-D Imaging Data

Bio-scaffolds which are most commonly open celled porous structures are increasingly used for tissue engineering and regenerative medicine. A number of studies have shown that the bulk properties of such irregular structures are poorly modeled using idealized unit cell approaches. The paper therefore uses novel image based meshing techniques to explore both fluid flow and bulk structural properties of a bone scaffold, as accurate modeling of bio-scaffolds with non-uniform cellular structures is very important for the development of optimal scaffolds for tissue engineering application. In this study, a porous hydroxyapatite/tricalcium phosphate (HA/TCP) bone scaffold has been scanned in a Micro-CT scanner, and converted into a volumetric mesh using image processing software developed by the authors. The resulting mesh was then exported to commercial FEA and CFD solvers for analysis. Initial FEA and CFD studies have shown promising results and have highlighted the importance of accurate modeling to understand how microstructures influence the mechanical property of the scaffold, and to analyze flow regimes through the sample. The work highlights the potential use of image based meshing for the ad hoc characterization of scaffolds as well as for assisting in the design of scaffolds with tailored strength, stiffness, and transport properties.     

Preparation of PLGA-collagen hybrid scaffolds with controlled pore structures for cartilage tissue engineering

Scaffolds used for cartilage tissue engineering should have high mechanical strength and well-controlled pore structure to provide suitable microenvironments for functional tissue regeneration. In this study, hybrid scaffolds which had open and interconnected pore structure and high mechanical property were prepared by hybridization of PLGA mesh and collagen using ice particulates as porogen templates. Embossing ice particulates template was used to form open pore structures on the scaffold surfaces. Free ice particulates were used to generate interconnected bulk pores in the scaffolds. Hybridization with PLGA mesh provided the scaffolds with high mechanical property. Bovine articular chondrocytes were cultured in the hybrid scaffolds. The unique pore structures facilitated the homogeneous distribution of chondrocytes and cartilaginous matrices throughout the scaffolds. Subcutaneous implantation demonstrated cartilage-like tissue regeneration. The hybrid scaffolds should have a high potential for cartilage tissue engineering.     

骨组织工程聚左旋乳酸多孔框架快速成形研究

为制备用于骨组织工程的细胞载体框架结构 ,对快速成形技术制备聚左旋乳酸多孔框架结构的若干基础问题进行了研究。提出了聚左旋乳酸快速成形的精密挤出成形工艺 ,研究了此工艺制备多孔框架结构的设备与工艺过程 ,分析了制备的多孔框架结构应用于组织工程人工骨的可行性。制备的多孔框架结构具有合适的分子量、孔隙结构、孔隙率、机械强度和生物降解性能 ,可以用作骨组织工程的组织再生框架结构     

3D打印制备HA/PCL复合材料组织工程支架的研究

应用熔融沉积成型技术（FDM）制备羟基磷灰石（HA）/聚己内酯（PCL）组织工程支架,探讨其内部结构和力学性能。以羟基磷灰石和聚己内酯为原料,采用熔融共混技术分别制备HA质量分数为20%的nano-HA/PCL和micro-HA/PCL复合材料,使用自主研发的熔体微分FDM 3D打印机制备HA/PCL复合材料组织工程支架。通过显微镜观察发现,所制备的nano-HA/PCL和micro-HA/PCL组织工程支架具有均匀分布且相互连通的近似矩形的孔隙。nano-HA/PCL和micro-HA/PCL组织工程支架的断面图分析结果表明,nano-HA/PCL组织工程支架中HA粒子分布均匀,而micro-HA/PCL组织工程支架中HA粒子发生了团聚,导致nano-HA/PCL组织工程支架的拉伸强度和弯曲强度均高于micro-HA/PCL组织工程支架。因此,利用熔体微分FDM 3D打印机打印生物活性nano-HA/PCL复合材料组织工程支架在骨组织工程中具有潜在的应用前景。     

组织工程三维多孔支架制备方法

随着老龄化社会的到来,组织工程的研究已成为现代生物医用工程技术中最为活跃的研究领域之一。三维多孔的组织工程支架作为骨组织工程学的关键环节,已成为近年来研究的热点。本文就近年来国内外三维多孔组织工程支架制备方法进行综述,希望能为今后的研究提供参考．     

Dexamethasone-Loaded PLGA Microspheres Incorporated PLLA/PLGA/PCL Composite Scaffold for Bone Tissue Engineering

The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.     

磷酸钙与胶原双相多级仿生骨组织工程支架研究

磷酸钙与胶原是天然骨组织的重要组成成分,介绍了一种仿生设计磷酸钙与胶原双相复合的多级仿生骨组织支架.采用双氧水发泡技术精确定制磷酸钙支架孔结构,结合真空灌注胶原以及仿生矿化技术,构建磷酸钙,胶原双相多级仿生骨组织支架,材料的孔结构及化学组分可实现定制设计.通过对支架材料测试表征,结果显示,这种无机/有机/无机多级仿生支架材有良好的力学性能.材料的体外细胞实验结果证实,这种多级仿生支架材料具有良好的生物相容性.     

Engineered polycaprolactone – magnesium hybrid biodegradable porous scaffold for bone tissue engineering

In this paper, we describe the fabrication of a new biodegradable porous scaffold composed of polycaprolactone(PCL) and magnesium(Mg)micro-particles. The compressive modulus of PCL porous scaffold was increased to at least 150% by incorporating 29% Mg particles with the porosity of 74% using Micro-CT analysis. Surprisingly, the compressive modulus of this scaffold was further increased to at least 236% when the silane-coupled Mg particles were added. In terms of cell viability, the scaffold modified with Mg particles significantly convinced the attachment and growth of osteoblasts as compared with the pure PCL scaffold. In addition, the hybrid scaffold was able to attract the formation of apatite layer over its surface after 7 days of immersion in normal culture medium, whereas it was not observed on the pure PCL scaffold. This in vitro result indicated the enhanced bioactivity of the modified scaffold. Moreover, enhanced bone forming ability was also observed in the rat model after 3 months of implantation. Though bony in-growth was found in all the implanted scaffolds. High volume of new bone formation could be found in the Mg/PCL hybrid scaffolds when compared to the pure PCL scaffold. Both pure PCL and Mg/PCL hybrid scaffolds were degraded after 3 months. However, no tissue inflammation was observed. In conclusion, these promising results suggested that the incorporation of Mg micro-particles into PCL porous scaffold could significantly enhance its mechanical and biological properties. This modified porous bio-scaffold may potentially apply in the surgical management of large bone defect fixation.     

仿生增强制备聚乳酸基骨组织工程复合材料

依据仿生原理制备了纳米羟基磷灰石聚乳酸(nHA-PLA)复合的骨框架材料.此复合材料中的主要成分是纳米羟基磷灰石,纳米相的羟基磷灰石就是天然骨中主要的无机相.在保持高孔隙率(90%)的同时,复合材料的抗压性能达到2.07 MPa,高于单纯的聚乳酸框架材料(为0.89 MPa).分离成骨细胞并在三维框架材料上培养,用扫描电镜进行观察,复合材料具有很好的细胞贴附性能.仿生制备的三维纳米羟基磷灰石聚乳酸复合骨框架材料,无论从结构还是性能上,都是骨组织工程中的优选材料之一.     

组织工程三维多孔支架制备技术的最新进展

理想的组织工程支架是由具有一定降解性能的高分子材料制成的,制备的支架除了要有一定的孔隙率和适于细胞生长的孔径外,还要有较高的机械性能和生物活性.为此介绍了用于组织工程中的可降解高分子材料,并详细阐述了最新的制备组织工程支架的方法:超临界CO2技术,计算机辅助成型技术,以及静电纺丝技术.     

细菌纤维素组织工程支架的仿生矿化研究

骨骼创伤已经成为当今影响人类健康的一大病症。因此,骨修复材料就成为研究的一大热点。骨组织工程支架作为重要的骨修复材料,可以诱导成骨细胞生长并为新骨生长提供条件。传统的骨组织工程支架包括合成高分子(如聚乳酸、聚乙醇酸等)和天然高分子(如胶原、壳聚糖等)。与传统支架材料相比,细菌纤维素(BC)具有良好的生物相容性、精细的纳米空间三维网络结构,有作为组织工程支架的潜能。通过仿生矿化处理,BC纳米纤维表面可以生长出羟基磷灰石(HA)的晶体颗粒,且HA颗粒均匀覆盖在纳米纤维表面。通过热分析得出,仿生矿化处理会使BC的热稳定性得到一定的提升。     

用于软骨下骨修复的镁基支架

骨关节炎（osteoarthritis，OA）作为一种可以导致残疾的退行性疾病，常累及软骨下骨。受损的关节软骨和软骨下骨很难自愈，用于功能修复的组织工程支架是一种有前途的治疗方法。近年来，镁合金因其良好的机械和生物学性能被视为可降解多孔支架有希望的候选者。然而，目前对于适用于软骨下骨缺损修复的镁基支架的结构设计和优化方案还没有定论。归纳了镁合金用于骨软骨支架的研究进展，包括多孔支架的制造方法；添加合金元素和表面改性的优化策略；参数化与非参数化的结构设计；镁基支架的机械、降解和生物学性能及其影响因素。讨论了未来研究的潜在方向。旨在为多孔镁基支架的开发和临床应用提供参考。     

气体发泡PLA/PS共混高聚物制备组织工程支架研究

相互联通的三维可控孔隙结构是组织工程支架材料设计的关键.介绍了一种通过气体物理发泡工艺制备多孔生物支架材料的方法,研究了对不可共混的双相高分子材料聚乳酸与聚苯乙烯进行可控发泡的设计,发泡后经溶蚀工艺处理得到相互联通的孔隙结构.成骨细胞种植实验结果显示,细胞在支架中生长情况良好,经2周培养初步表现出在三维空间蔓延传递生长的特征,表明此方法为制备三维可控多孔类组织工程支架材料提供了一种有效设计途径.     

聚乙烯醇-透明质酸-胶原组织工程支架研究

以聚乙烯醇(PVA)、透明质酸(HA)和胶原蛋白(Col)为组分,构建组织工程三维多孔支架.将聚乙烯醇分别与不同质量的胶原和透明质酸复合,测定复合材料的含水率和膨胀率.扫描电镜观察材料横截面的表面形态.结果是不同分子质量的PVA与不同配比的Col和HA复合,得到的复合支架材料含水率为57.97%～81.26%,膨胀率为150.00%～459.20%.不同配比的复合支架材料具有不同的内部孔洞结构.结果表明,PVA-HA-Col复合支架材料具有较高的含水率和膨胀率,内部孔洞网络丰富,可作为组织工程支架材料.     

Preparation and evaluation of biomimetric nano-hydroxyapatite-based composite scaffolds for bone-tissue engineering

In the present study,novel biomimetic composite scaffolds with a composition similar to that of natural bone were prepared,using nano-hydroxyapatite,collagen,and phosphatidylserine.The scaffolds possess an interconnected porous structure with a porosity of 84%.The pore size ranges from several micrometers up to about 400 m.In-vitro studies in simulated body fluids showed that the morphologies of the products derived from mineralization can be regulated by the extracellular matrix components of the scaffolds;this in turn leads to creation of a large number of hydroxyapatite crystals on the scaffold surface.The regulatory properties of collagen and phosphatidylserine also influenced the cell response to the composite scaffolds.MC3T3-E1 cells attached and spread on the surfaces of the materials and interacted with the substrates;this may be the result of charged groups on the composite materials.Radiological analysis suggested that calluses and bone bridges formed in defects within 12 weeks.These composite scaffolds may therefore be a suitable replacement in bone-tissue engineering.     

Aerodynamically Assisted Tip-Pen Direct Writing

Scaffolds require individual external shape and well-defined internal structure, which is of great importance for tissue engineering. Rapid prototyping (RP) uses layer-manufacturing strategies to create physical objects and has the advantage on scaffold fabrication. A new RP technology called aerodynamically assisted tip-pen direct writing was developed to construct the complex architectures. Compared with the traditional nozzle, the new nozzle has a micro-tip in the center of the micro-hole. The flow is determined by the gap between the micro-hole and micro-tip, which makes it practical for more accurate flow control. A highly accurate three-dimensional (3-D) micro-positioning system was employed with the new nozzle to deposit maltose structures. 3-D architectures had been made by this method, the width of fiber in which is about 120 μm. The results show that this method provides a possibility to construct 3-D scaffolds with tissue-scale features (i.e., 10–100 μm) without bad influence on the biological activities.     

3D Nanocomposite Hydrogel Scaffolds Fabricated by Rapid Prototyping for Bone Tissue Engineering

Colloidal gels made of oppositely charged nanoparticles are a novel class of hydrogels and can exhibit pseudoplastic behavior which will enable them to mold easily into specific shapes. These moldable gels can be used as building blocks to self-assemble into integral scaffolds from bottom to up through electrostatic forces. However, they are too weak to maintain scaffold morphology just depending on interparticle interactions such as Van der Waals attraction and electrostatic forces especially for bone tissue engineering. In this study, oppositely charged gelatin nanoparticles were firstly prepared by two-step desolvation method, followed by the mixture with water to form colloid gels. To solve the problem of weak mechanical performance of colloid gels, gelatin macromolecules were introduced into the prepared gels to form blend gels. The blend gels can be easily processed into three-dimensional （3D） porous scaffolds via motor assisted microsyringe （MAM） system, a nozzle-based rapid prototyping technology, under mild conditions. After fabrication the scaffolds were erosslinked by glutaraldehyde （ GA, 25 % solution in water by weight）, then the crosslinked gelatin macromolecules network could form to improve the mechanical properties of colloid gels. The average particle size and zeta potential of gdatin nanoparticles were measured by Nano- ZS instrument. The morphology and microstructures of scaffolds were characterized by macroscopic images. The mechanical properties of the scaffolds were studied by a universal material testing machine.     

新型前交叉韧带支架材料的构建及其生物相容性的实验研究

探讨以聚羟基丁酸己酯/聚左旋乳酸(PHB/PLLA1∶1)胶原杂化支架作为前交叉韧带组织工程载体材料的可行性。制备"三明治"样结构PHB/PLLA共聚物并测量其孔隙率等指标。以I型胶原对制备的PHB/PLLA支架进行杂化,获得PHB/PLLA胶原杂化支架。扫描电镜观察其表面结构。将兔皮肤成纤维细胞(SF)接种于PHB/PLLA胶原杂化支架,共培养5d后,扫描电镜下观察其在材料上生长情况。PHB/PLLA支架杂化后胶原填充于纤维空隙,分布比较均匀。体外培养的皮肤成纤维细胞成功种植在支架材料上,在材料上粘附、生长良好。说明构建的支架材料具有良好的三维构型和生物相容性,有望为前交叉韧带损伤的修复提供了一种新型的支架材料。     

纳米相陶瓷支架与人成骨细胞生物相容性的体外实验研究

研究了2种新型多孔纳米陶瓷支架材料(hydroxyapatite,HA和tricalcium phosphate,TCP)的生物相容性.从人4月龄胚胎骨膜组织中分离培养出骨膜来源的成骨细胞(periosteal-derived osteoblast,POB),采用人胚骨膜成骨细胞与2种陶瓷支架的体外复合培养,观察细胞在材料上的生长及生理功能表达情况.发现人POB在HA和TCP表面生长繁殖良好,并发挥成骨功能.材料对细胞的增殖还有一定的促进作用(p<0.05).实验表明: 2种新型多孔陶瓷支架材料均有良好的生物相容性.     

高链玉米淀粉对聚己内酯组织工程支架材料结构与性质的影响

采用高链玉米淀粉改性聚己内酯（PCL）,通过溶剂浇铸/粒子沥滤法制备聚己内酯/淀粉（SPCL）组织工程支架;考察了改性后支架材料的化学结构、结晶性、亲水性和细胞相容性.结果表明,适量淀粉的引入能够降低支架材料的结晶性、改善材料的亲水性和细胞相容性,70％PCL/30％淀粉支架材料的细胞粘附率、增殖率和细胞活性为最佳,有望应用在骨组织工程中.