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

机译：通过集成3D印刷和超临界CO2发泡脚手架的定向发泡

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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：介绍：软骨修复是一个挑战性的临床问题，因为一旦成人受损，它就不会再生，导致缺陷可能进一步导致骨关节炎。组织工程作为可能解决问题的可能解决方案。其中一个挑战是产生最佳支架，能够再现自然ECM并在植入过程的早期携带组织功能，同时诱导再生。虽然适用于处理生物材料的许多技术，但是作为超临界发泡和添加剂制造的物理方法代表了控制最终构建体的精确组成的清洁方法。这项工作代表了第一次尝试将这两种技术的优点结合在克服一些主要缺点，产生3D各向异性尺寸控制的结构。方法：使用融合沉积建模来使用Ultimaker原始+来生产原料脚手架。首先是从PLA自然工作4043D和2003D创建的纤维，分别从Fileoalfa和TreedfiLy获得。纤维。为每个PLA异构体印刷三个2D结构，尺寸为10mm×10mm×1mm，内窗3.5mm×3.5mm。然后，从每个PLA制造三个3D支架，（4.4mm×4.4mm×4.4mm，0.4mm纤维和0.6mm纤维间距）。然后，从Sitec Sieber工程AGPI的GMP医用高压釜中，每个2D和3D结构都用超临界CO2发泡。通过UCT（微锁定技术Inc.Skyscan 1076，比利时）和扫描电子显微镜（SEM）测定孔隙率，孔径分布，互连和支架膨胀后发泡后发泡后发泡后发泡（SEM）。采用终极拉伸强度机（德国试验机系统）研究了压缩行为。结果：通过调节发泡参数，提供所需的蜂窝架构，在微米范围内具有光纤定向孔隙度（图1），获得最小架构变形和最大互连孔隙率。图1：（左）之前和（右）超临界发泡之前的支架。得到一系列机械性能，从固体到发泡细胞材料，从而用固体壁降低支架的刚度并引入与纤维的取向有关的各向异性特性。最后提出了一种从3D印刷结构到3D发泡结构的扩展模型。讨论和结论：结果表明，克服3D印刷支架的孔隙率极限和泡沫的各向异性控制。通过组合3D添加剂制造和超临界发泡来获得3D结构中的均相宏观和面向微孔隙的各向异性，两种可整合活细胞的无溶剂方法获得。我们目前正在调查将其应用于医疗级PLA和生物材料中作为聚乙醇酸（PGA）和聚己内酯（PCL）。

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