Osteogenic Differentiation of Human Mesenchymal Stem cells in a 3D Woven Scaffold

Scientific Reports, Jul 2018

Fiber-based scaffolds produced by textile manufacturing technology offer versatile materials for tissue engineering applications since a wide range of crucial scaffold parameters, including porosity, pore size and interconnectivity, can be accurately controlled using 3D weaving. In this study, we developed a weavable, bioactive biodegradable composite fiber from poly (lactic acid) (PLA) and hydroxyapatite powder by melt spinning. Subsequently, scaffolds of these fibers were fabricated by 3D weaving. The differentiation of human mesenchymal stem cells (hMSCs) in vitro was studied on the 3D scaffolds and compared with differentiation on 2D substrates having the same material composition. Our data showed that the 3D woven scaffolds have a major impact on hMSCs proliferation and activation. The 3D architecture supports the differentiation of the hMSCs into osteoblast cells and enhances the production of mineralized bone matrix. The present study further confirms that a 3D scaffold promotes hMSCs differentiation into the osteoblast–lineage and bone mineralization.

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Osteogenic Differentiation of Human Mesenchymal Stem cells in a 3D Woven Scaffold

Abstract Fiber-based scaffolds produced by textile manufacturing technology offer versatile materials for tissue engineering applications since a wide range of crucial scaffold parameters, including porosity, pore size and interconnectivity, can be accurately controlled using 3D weaving. In this study, we developed a weavable, bioactive biodegradable composite fiber from poly (lactic acid) (PLA) and hydroxyapatite powder by melt spinning. Subsequently, scaffolds of these fibers were fabricated by 3D weaving. The differentiation of human mesenchymal stem cells (hMSCs) in vitro was studied on the 3D scaffolds and compared with differentiation on 2D substrates having the same material composition. Our data showed that the 3D woven scaffolds have a major impact on hMSCs proliferation and activation. The 3D architecture supports the differentiation of the hMSCs into osteoblast cells and enhances the production of mineralized bone matrix. The present study further confirms that a 3D scaffold promotes hMSCs differentiation into the osteoblast–lineage and bone mineralization. Introduction The major challenge in tissue engineering is to design an ideal scaffold that mimics the three-dimensional (3D) architecture and intrinsic properties of natural tissues or organs. Despite significant efforts in the field, the design requirements for various tissue engineering scaffolds have still not been defined precisely. The pore sizes, together with the porosity, are known to play crucial roles in regulating the morphology and behavior of different cell types1,2,3. The pore sizes required by various cell types differ, and usually pore sizes of several 100 µm are necessary for efficient cell growth, migration and nutrient flow. However, large pore sizes decrease the surface area, limit cell adhesion and prevent the formation of cellular bridges across the structure4. Large pores also diminish the mechanical properties of the scaffold due to increased void volume, which is another critical parameter in scaffold design5. For scaffolds intended to be used for bone regeneration it has been reported that a pore size in the range of 150–400 µm is optimal to promote bone formation and vascularization within the scaffold2,3,6. However, it should be noted that the optimal pore size range is also influenced by the material of the scaffold, its size, as well as vascularization of the surrounding tissues6. Several methods and materials have been applied in combination with multidisciplinary approaches to find the optimal design for the biofabrication of 3D porous scaffold systems for tissue engineering applications7,8. Among these processing techniques are methods such as solvent casting, and particulate leaching, gas foaming, emulsion freeze-drying, thermally induced phase separation and rapid prototyping. 3D printing has aroused interest since it is a direct computerized “layer by layer” method to manufacture scaffolds with designed shape and porosity. A major challenge for these techniques is to simultaneously optimize the mechanical properties with an adequate porosity and they still present low reproducibility in combination with high costs9,10. For these reasons, far too little attention has been paid to micro-fiber and textile technologies. The human body has various natural fiber structures, mainly collagens within the connective tissue. Muscles, tendons and nerves are also fibrous in nature and therefore cells are used to fibrous structures11. Electrospinning, a biofabrication technique capable of producing fibers in the submicro- and nanoscale range, has been widely studied and used in the design of TE scaffolds4,12. However, the small fiber diameter in the submicro-and nanoscale range results in low porosity and small pore size, which greatly limits cell infiltration and cell migration through the thickness of the scaffold. When implanted into the body, such electrospun scaffolds will likely loosen over time, which requires re-surgery. In this regard, micro-fibers processed with textile manufacturing technology such as knitting, braiding, weaving or nonwoven can be considered as a potential solution for the biofabrication of complex scaffolds for tissue engineering applications. Such technologies indeed present superior control over the design, manufacturing precision and reproducibility13. In addition, the scaffold can further be influenced on a hierarchical level by altering the chemical and/or mechanical properties of the fibers14,15. Using such an approach, Moutos et al. reported in 2007 a breakthrough in the scaffold design for the functional tissue engineering of cartilage. They used textile technology to design a biomimetic 3D woven composite scaffold that exhibits and maintains properties similar to those of cartilage14. Since then a number of successful studies have been reported using textile technologies to develop scaffolds for different biological tissues12,13,16,17,18,19,20,21,22,23,24,25. Clearly, the use (...truncated)


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Maria Persson, Petri P. Lehenkari, Lena Berglin, Sanna Turunen, Mikko A. J. Finnilä, Juha Risteli, Mikael Skrifvars, Juha Tuukkanen. Osteogenic Differentiation of Human Mesenchymal Stem cells in a 3D Woven Scaffold, Scientific Reports, 2018, Issue: 8, DOI: 10.1038/s41598-018-28699-x