It is well known that cell shape determines cell function. The technology of altering cell shape by changing the biophysical properties of the biomaterial substrate used for cell manipulation, thereby programming cell morphology and function, has significant value and implications in fields such as biomedicine.
A team of researchers at MIT’s Bit and Atom Center and Stevens Institute of Technology in New Jersey has developed a technique for creating 3D biomaterial substrates using melt-to-write. This technique allows for the growth of cells with uniform size and shape, as well as specific functions, by controlling the specific biomaterial substrate.
Traditional 3D printing technology produces filaments down to 150 micrometers (one millionth of a meter). Cells printed at this scale appear almost like cells on a two-dimensional surface because the cells themselves are much smaller than the printed mesh structure. During 3D printing, a strong electric field is applied between the nozzles during fiber extrusion and printing, allowing for fiber widths down to 10 micrometers. This technology is called fused direct writing. Fused direct writing can generate mesh structures at the same scale as cells, providing a true 3D structure for cell growth. Many cellular functions are influenced by their microenvironment. By adjusting the porous microstructures printed at the same scale as cells, it is possible to control the cell size, shape, and adhesion to the material substrate—that is, to create cells with specific sizes, shapes, and properties.
The team first used melt direct writing technology to obtain biological substrates with various specific structures, then used confocal microscopy to observe cell growth in fibers, and used artificial intelligence methods to analyze and classify the large number of images generated, thereby discovering the correlation between cell type and its variability and the spatial and fiber arrangement characteristics of the microenvironment in which it grows.
Cells form proteins called "focals" at the sites where they attach to structures. Focals act as "messengers" for cells to communicate with the outside world, and these proteins carry measurable features. The team quantified these features on the focals and performed quantitative analysis on them to model and classify cells of different shapes.
This study demonstrates that, given a mesh structure, the shape of cells that grow is directly coupled to its basal structure and fused direct-write structure. Furthermore, this coupling exhibits a high degree of uniformity compared to mesh structures with random structures. This uniform cell growth characteristic is of great significance to biomedicine—it enables a shape-driven method for the precise design and quantification of cells with high repeatability.
The team applied this finding to stem cell growth, demonstrating that specific stem cells grown in the 3D mesh obtained in this study retained their properties for a significantly longer time compared to growth in traditional 2D structures. This experiment provides a reference for the application of this technology in the medical field, enabling the cultivation of human cells with specific functions, thereby providing the necessary materials for transplantation and artificial organs. Further clarifying the coupling characteristics between cell phenotypic changes and the 3D-printed material substrate remains the main obstacle to the industrialization of this research.
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