Calore Andrea Roberto, Srinivas Varun, Groenendijk Linda, Serafim Andrada, Stancu Izabela Cristina, Wilbers Arnold, Leoné Nils, Sanchez Ane Albillos, Auhl Dietmar, Mota Carlos, Bernaerts Katrien, Harings Jules A W, Moroni Lorenzo
MERLN Institute for Technology-Inspired Regenerative Medicine, Complex Tissue Regeneration department, Maastricht University, Maastricht, the Netherlands; Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Geleen, the Netherlands.
Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Geleen, the Netherlands.
Acta Biomater. 2023 Jan 15;156:158-176. doi: 10.1016/j.actbio.2022.07.017. Epub 2022 Jul 19.
Manufacturing of three-dimensional scaffolds with multiple levels of porosity are an advantage in tissue regeneration approaches to influence cell behavior. Three-dimensional scaffolds with surface roughness and intra-filament open porosity were successfully fabricated by additive manufacturing combined with chemical foaming and porogen leaching without the need of toxic solvents. The decomposition of sodium citrate, a chemical blowing agent, generated pores within the scaffold filaments, which were interconnected and opened to the external environment by leaching of a water-soluble sacrificial phase, as confirmed by micro-CT and buoyancy measurements. The additional porosity did not result in lower elastic modulus, but in higher strain at maximum load, i.e. scaffold ductility. Human mesenchymal stromal cells cultured for 24 h adhered in greater numbers on these scaffolds when compared to plain additive-manufactured ones, irrespectively of the scaffold pre-treatment method. Additionally, they showed a more spread and random morphology, which is known to influence cell fate. Cells cultured for a longer period exhibited enhanced metabolic activity while secreting higher osteogenic markers after 7 days in culture. STATEMENT OF SIGNIFICANCE: Inspired by the function of hierarchical cellular structures in natural materials, this work elucidates the development of scaffolds with multiscale porosity by combining in-situ foaming and additive manufacturing, and successive porogen leaching. The resulting scaffolds displayed enhanced mechanical toughness and multiscale pore network interconnectivity, combined with early differentiation of adult mesenchymal stromal cells into the osteogenic lineage.
制造具有多级孔隙率的三维支架在影响细胞行为的组织再生方法中具有优势。通过增材制造结合化学发泡和致孔剂浸出，成功制造出具有表面粗糙度和丝内开放孔隙率的三维支架，无需使用有毒溶剂。化学发泡剂柠檬酸钠的分解在支架丝内产生孔隙，这些孔隙通过水溶性牺牲相的浸出相互连通并通向外部环境，这已通过显微CT和浮力测量得到证实。额外的孔隙率并未导致较低的弹性模量，而是在最大载荷下产生了更高的应变，即支架延展性。与普通增材制造的支架相比，无论支架预处理方法如何，培养24小时的人间充质基质细胞在这些支架上的附着数量更多。此外，它们表现出更铺展和随机的形态，已知这种形态会影响细胞命运。培养较长时间的细胞在培养7天后表现出增强的代谢活性，同时分泌更高水平的成骨标志物。重要性声明：受天然材料中分层细胞结构功能的启发，这项工作阐明了通过原位发泡、增材制造和连续致孔剂浸出来开发具有多尺度孔隙率的支架。所得支架显示出增强的机械韧性和多尺度孔隙网络互连性，同时成年间充质基质细胞早期分化为成骨谱系。
