Single-Cell Resolution: New Method for Tissue Fabrication

Recent advances in extremely high-resolution biofabrication (e.g., at the single cell level) have significantly increased the capacity of biofabrication and opened new avenues for tissue engineering. However, a comprehensive review summarizing various biofabrication technologies (besides bioprinting) that could achieve single-cell resolution (besides single-cell manipulation) and nevertheless cover applications in biomedicine is lacking. Scientists from Tsinghua University have provided a perspective to assess progress in the biofabrication of engineered living systems at single-cell resolution.

The research interests of Dr.’s team Ouyang encompass the design, fabrication and application of complex biomaterial and cellular systems, with a central focus on the development of 3D bioprinting and advanced biofabrication technologies for tissue engineering and regenerative medicine. Since cells are the basic units of the living systems, they believe that the engineering living systems with single-cell characteristics are important to recapitulate the microenvironment in the native tissues.

This review, published in International Journal of Extreme Manufacturing, provides an overview of biomanufacturing methods based on the modular assembly of cellular building blocks with single-cell features in different dimensions and provides an informative introduction to the most recent developments.

“Heterogeneity at single-cell resolution is a common phenomenon within natural living systems, so the techniques to manipulate the individual cells to reconstruct the engineered living systems are valuable. But several factors, such as the mechanical strength of the products and the efficiency of the manufacturing, should be well thought out, and it is important to select the right single-cell building blocks for a specific use,” said Dr. Liiang Ouyang, associate professor of Mechanical Engineering at Tsinghua University and senior author of the review.

“In principle, the size of the building blocks would determine the minimum feature of the structure and it takes longer to assemble a large-scale cellular structure with smaller building blocks. To achieve high resolution and fabrication efficiency at the same time, we propose a modular assembly strategy, enabling co-assembly of building blocks of different sizes to form desired heterostructures,” said Dezhi Zhou, a Ph.D. student and the first author of the article.

Each type of tissue/organ has its unique structure to realize its function. For example, pancreatic islets are composed of at least five types of cells, which form special junctions within a dimension of different cells, to maintain blood glucose homeostasis via cell-cell interaction; Skeletal muscle is an anisotropic tissue containing bundled muscle bundles enveloped by the epimysium, and the muscle bundles exhibit normal function by controlling the transition between relaxation and contraction. Alveolus is another example, which consists of multiple layers surrounded by a network of capillaries for gas exchange. Due to the unique multi-layer structure with a thickness of a few micrometers, a large surface area (100–140 m) can be achieved.²) for effective gas exchange. Therefore, it is fundamental to rebuild these topological structures to guarantee the function of the technical living systems.

“Just like playing LEGO, we select the right blocks and put them together to make what we want,” says Zhou. This is extremely helpful in building a complex structure to mimic natural living systems. “But for scientists it is an ongoing challenge to create the right living building blocks and assemble them in a controlled manner,” says Dr. Ouyang.

Based on the ‘dispersion-deposition’ principle, complex living systems can be considered as a collection of several distinct elements, including single cell function building blocks and cell population/biomaterial building blocks. Then the counterparts of each individual element can be generated and placed together to rebuild the desired object. “We believe that the combination of these two building blocks can contribute to the development of complex tissues with both physicochemical and biological characteristics,” says Zhou.

About IJEM:

International Journal of Extreme Manufacturing (IF: 14.7, 1st in Engineering, Manufacturing category in JCR 2023) is a new multidisciplinary, double-anonymous peer-reviewed and diamond open-access journal with no article processing fees that uniquely covers the full spectrum of extreme production covers . The journal is dedicated to publishing original articles and reviews of the highest quality and impact in the areas related to the science and technology of manufacturing functional devices and systems with extreme dimensions (extremely large or small) and/or extreme functionalities ranging from basic science to advanced technologies that support the production of high-quality products with emerging techniques and that break the boundaries of currently known theories, methods, scales, environments and performance.

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