3-D Printing for Life Science Applications

Bioprinting: From concept to reality

The human cell represents the smallest functional unit of life. All tissues in the body are composed of multiple cell types, typically arranged in a 3-D architecture that is relevant to the functions they carry out. Since cells were first isolated and grown in the laboratory environment, biologists and engineers have pursued the utilization of these tiny building blocks in the reconstruction and regeneration of functional tissue. Whether used in a controlled laboratory setting to model specific diseases and test the effects of drugs, or delivered into the body as therapeutics for the treatment of disease, the common goal is to establish or re-establish in vivo-like function.

The field of tissue engineering has deployed several fabrication strategies aimed at bringing cells and structure together to generate tissue. Biomaterial scaffolding—which provides structural support and can be formed into biologically relevant shapes—has been combined with cells to generate hybrid 3-D structures for use as tissue surrogates in vitro and in vivo. Protocols have been developed that enable removal of living cells from native tissues, leaving only a natural scaffolding of extracellular matrix, which can then be re-seeded with cells to reconstruct or partially reconstruct 3-D tissues. Another approach to soft tissue reconstruction has been the development of cell-laden hydrogels, which are often cast into a specific shape and placed into a permissive environment in vitro or in vivo that allows maturation and establishment of tissue-specific characteristics. In recent years, with the advancement of 3-D printing technologies for the on-demand fabrication of complex polymer-based objects, efforts have been underway to adapt 3-D printing technologies and engineer bioprinting instruments that can leverage similar 3-D replication concepts and accommodate the incorporation of living cells.

First-generation 3-D prototyping techniques relied on subtractive processes—the removal of material from a solid block using filing, milling, drilling, cutting and grinding methods. Advanced 3-D prototyping technologies utilize additive processes in which the desired part is built up—or “printed” layer-by-layer. Objects of virtually any shape can now be fabricated from a wide range of non-biological materials using additive technologies.

The power and utility of 3-D printing in the non-biological materials area has sparked the imaginations of biologists and engineers alike and fueled R&D activities aimed at producing intricate biological 3-D structures. Consequently, precise, automated, layer-by-layer fabrication of tissue (bioprinting) is now possible using only living cells as building blocks. This is resulting in simultaneous achievement of unique features such as true 3-D, tissue-like cellular densities and reproduction of native tissue architecture through the spatially directed placement of distinct cell types.

Bioprinting hardware requires unique features that ensure success at the interface of engineering and biology.

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