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Directional foaming of scaffolds by integration of 3D printing and supercritical CO2 foaming

机译:通过集成3D打印和超临界CO2发泡进行支架的定向发泡

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Introduction: Cartilage repair is a challenging clinical problem because once damaged in adults, it never regenerates and resulting defects may further lead to osteoarthritisl1'. Tissue Engineering has emerged as a possible solution to the problem. One of the challenges is to produce an optimum scaffold, able to reproduce the natural ECM and to carry tissue functions in the early stage of the implant process, while inducing the regeneration. While many techniques as applied to process biomaterials, physical methods as supercritical foaming and Additive Manufacturing represent a clean way to control the exact composition of the final construct. This work represents a first attempt to combine the advantages of the two techniques while overcoming some of the main drawbacks, producing 3D anisotropic size-controlled structures. Methods: An Ultimaker Original+ was used to produce the raw scaffold by fusion deposition modelling. Fibers were first created from PLA Natureworks 4043D and 2003D acquired respectively from FiloAlfa and TreeDFilament. Fibers. Three 2D structures were printed for each PLA isomer, with a dimension of 10mm × 10mm × 1mm and with inner windows of 3.5mm × 3.5mm. Then, three 3D scaffolds were produced from each PLA, (4.4mm × 4.4mm × 4.4 mm, 0.4mm fibers and 0.6mm fibers spacing). Each 2D and 3D structure was then foamed with supercritical CO2 in a GMP medical autoclave from SITEC SIEBER Engineering AGPI. Porosity, pore size distribution, interconnectivity and scaffold expansion post foaming were determined by uCT (Microcomputed Technologies Inc. Skyscan 1076, Belgium) and Scanning Electron Microscopy (Microscopy XLF30 microscope) (SEM). Compression behaviour was investigated with an Ultimate Tensile Strength machine (Test Machine Systeme, Germany). Results: The minimum architecture deformation and the maximum interconnected porosity were obtained by tuning the foaming parameters, offering the desired cellular architectures, with fibre directional porosity in the micro meter range (Figure 1). Fig. 1: Scaffold before (left) and after (right) supercritical foaming. A range of mechanical properties were obtained, from solid to foamed cellular material, reducing the stiffness of scaffolds with solid walls and introducing anisotropic properties related to the orientation of the fibres. A model of expansion from 3D printed structure to 3D foamed structure is finally proposed. Discussion and Conclusions: The results shows a possibility to overcome the porosity limit of 3D printed scaffold and anisotropy control of foams. A controlled anisotropy, a homogeneous macro- and an oriented micro-porosity in 3D structures are obtained by combining 3D additive manufacturing and supercritical foaming, two solvent-free processes which could integrate living cells. We are currently investigating the possibility to apply it to medical grade PLA and biomaterials as Polyglycolic acid (PGA) and Polycaprolactone (PCL).
机译:简介:软骨修复是一个具有挑战性的临床问题,因为一旦在成人中受损,它就不会再生,并且所产生的缺陷可能进一步导致骨关节炎[1]。组织工程学已经出现,可以解决该问题。挑战之一是如何生产出最佳的支架,该支架能够在植入过程的早期阶段复制天然的ECM并具有组织功能,同时又能诱导再生。尽管许多技术用于处理生物材料,但物理方法(如超临界发泡和增材制造)代表了一种控制最终构造物确切组成的干净方法。这项工作代表了结合这两种技术的优点同时克服一些主要缺点的首次尝试,从而产生了3D各向异性尺寸控制的结构。方法:使用Ultimaker Original +通过融合沉积建模生产原始脚手架。纤维是首先从分别从FiloAlfa和TreeDFilament获得的PLA Natureworks 4043D和2003D创建的。纤维。为每种PLA异构体打印了三个2D结构,尺寸为10mm×10mm×1mm,内部窗口为3.5mm×3.5mm。然后,从每个PLA生产三个3D支架(4.4mm×4.4mm×4.4mm,0.4mm纤维和0.6mm纤维间距)。然后在SITEC SIEBER Engineering AGPI的GMP医用高压釜中,将每个2D和3D结构与超临界CO2一起发泡。发泡后的孔隙率,孔径分布,互连性和支架膨胀通过uCT(Microcomputed Technologies Inc. Skyscan 1076,Belgium)和扫描电子显微镜(Microscopy XLF30显微镜)(SEM)进行测定。用极限拉伸强度机(Test Machine Systeme,德国)研究压缩行为。结果:通过调节起泡参数可获得最小的结构变形和最大的互连孔隙率,从而提供所需的多孔结构,且纤维定向孔隙率在微米范围内(图1)。图1:超临界发泡之前(左侧)和之后(右侧)的脚手架。从固体材料到泡沫多孔材料,获得了一系列机械性能,从而降低了具有实心壁的脚手架的刚度,并引入了与纤维取向有关的各向异性。最后提出了一种从3D打印结构扩展到3D泡沫结构的模型。讨论与结论:结果表明,有可能克服3D打印支架的孔隙率极限和泡沫的各向异性控制。通过将3D增材制造和超临界发泡相结合,获得了可控制的各向异性,3D结构中均匀的宏观和定向的微孔,这两个无溶剂过程可以整合活细胞。我们目前正在研究将其应用于医用级PLA和聚乙醇酸(PGA)和聚己内酯(PCL)等生物材料的可能性。

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