Architecturally Correct Tissue

Every tissue in the body is composed of multiple cell types that are positioned relative to each other with a high degree of specificity. Most normal tissues have a pattern or repeating pattern that is created by the natural compartmentalization of different cell types within the tissue. Many tissue patterns can be appreciated by cutting thin sections of the tissue and subjecting them to staining procedures that highlight tissue features.

The following examples highlight the lobulated structure of the liver, the laminar or layered architecture of the blood vessel wall, or the islands-and-sea pattern of glandular tissues such as prostate, breast, or thyroid.

liver_blood_breast tissue
Histologic micrographs of native human tissue (Left to right: Liver, blood vessel, and breast tissue).

When cells are isolated from tissues and maintained outside of the body, they are typically purified to eliminate other cell types. Subsequently the cells are cultured as monolayers of cells on sterile plasticware that is specially treated to foster cell adhesion in a 2D architecture. The benefits of having multiple cell types present and in a 3D architecture are lost; this is often accompanied by loss of tissue-specific function. By restoring the 3D architecture of the tissue and building the tissue with multiple cell types, bioprinting enables re-establishment of in vivo-like form and function.

The true functionality of any tissue is dependent on the presence of specific cell types and the milieu that is created by those cells as they secrete proteins that provide the tissue with structure and soluble proteins that act locally and systemically to support homeostasis of a living organism. In fact, the majority of disease processes are characterized by obvious disruptions in tissue architecture that reflect cell-specific damage or loss. For example, long-term exposure to alcohol can lead to cirrhosis, or the accumulation of scar tissue, in the liver, which produces obvious changes in the tissue. Acute exposure to high doses of drugs that are toxic to the liver, like acetaminophen, can lead to death of liver cells and necrosis, which also presents a clear change in the pattern associated with liver tissue.

liver_cirrhotic

An example of native human liver fibrosis or cirrhosis.

liver_necrotic

An example of drug-induced necrosis in native human liver tissue