Abstract
Tissue engineering is a multi-disciplinary area of research bringing together the fields of engineering and life sciences with the aim of fabricating tissue constructs aiding in the regeneration of damaged tissues and organs. Scaffolds play a key role in tissue engineering, acting as the templates for tissue regeneration and guiding the growth of new tissue. The use of stem cells in tissue engineering and regenerative medicine becomes indispensable, especially for applications involving successful long-term restoration of continuously self-renewing tissues, such as skin. The differentiation of stem cells is controlled by a number of cues, of which the nature of the substrate and its innate stiffness plays a vital role in stem cell fate determination. By tuning the substrate stiffness, the differentiation of stem cells can be directed to the desired lineage. Many studies on the effect of substrate stiffness on stem cell differentiation has been reported, but most of those studies are conducted with two-dimensional (2D) substrates. However, the native in vivo tissue microenvironment is three-dimensional (3D) and life science researchers are moving towards 3D cell cultures. Porous 3D scaffolds are widely used by the researchers for 3D cell culture and the properties of such scaffolds affects the cell attachment, proliferation, and differentiation. To this end, the design of porous scaffolds directly influences the stem cell fate determination. There exists a need to have 3D scaffolds with tunable stiffness for directing the differentiation of stem cells into the desired lineage. Given the limited number of biomaterials with all the desired properties, the design of the scaffolds themselves could be used to tune the matrix stiffness. This paper is an in silico study, investigating the effect of various scaffold parameter, namely fiber width, porosity, number of unit cells per layer, number of layers, and material selection, on the matrix stiffness, thereby offering a guideline for design of porous tissue engineering scaffolds with tunable matrix stiffness for directing stem cell lineage specification.
Highlights
The term ‘tissue engineering’ was officially coined at a National Science Foundation workshop in 1988 to mean “the application of principles and methods of engineering and life sciences toward the fundamental understanding of structure-function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain, or improve tissue function” [1]
The field of tissue engineering aims to regenerate damaged tissues by combining cells from the body with highly-porous scaffold biomaterials, which act as templates for tissue regeneration, to guide the growth of new tissue
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Summary
The term ‘tissue engineering’ was officially coined at a National Science Foundation workshop in 1988 to mean “the application of principles and methods of engineering and life sciences toward the fundamental understanding of structure-function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain, or improve tissue function” [1]. Mechanical properties of the substrate play a very important role in determining the differentiation of stem cells. The scaffold properties, especially the stiffness, determine, to a large extent, the differentiation of stem cells into the neural lineage, muscle lineage, or bone lineage. There were detailed studies on how matrix stiffness governs the stem cell fate determination and the underlying mechanism [8,9,10]. Most of these studies are done on two-dimensional substrates. It is highly likely that, in 3D cultures, stem cell differentiation may be regulated differently, through the mechanical stiffness of the substrate. Given the limited number of biomaterials with all the desired properties, design of the scaffolds themselves could be used to tune the matrix stiffness
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