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The primary objective of tissue engineering is to understand the principles of tissue growth and to apply this to produce functional replacement tissue. Such tissue can be used to restore, maintain, or improve damaged tissues or whole organs. By 2005, engineered artificial skin and cartilage tissues had been approved by the FDA, however had limited use in human patients.
Tissue engineering is a subset of regenerative medicine, a field which deals with the process of replacing, engineering, or regenerating biological units to (re-)establish normal function using the body's self-healing capabilities. Tissue engineering focuses on cures, rather than treatments, for diseases related to biological tissues.
The field is multidisciplinary in nature, requiring collaborations between cell and molecular biology, clinicians, materials scientists, mathematicians, and more. For example, mathematical models are used to form a holistic understanding of complex biological processes in evolving tissues. The combination of biomimetic materials science and stem cell biology with mathematical models is used to determine which tissue engineering strategies are most likely to be successful. Such an integration of mathematical models with experimentation in an iterative framework where each informs the other offers a way to better understand tissue regeneration.
Cells are the building blocks of tissues. Groups of cells make their own support structures, called extra-cellular matrices, or scaffolds. Scaffolds mechanically support cells and act as a relay station for various signaling molecules in the body. When a signal is received, it initiates a chain of responses that affect the cell. By better understanding how cells respond to signals, interact with their environments, and organize themselves into tissue and organisms, researchers are able to manipulate these processes to mend damaged tissues or create new ones.
In tissue engineering, a scaffold is built from a variety of sources, ranging from proteins to plastics. Cells are introduced to the scaffold with or without a mix of growth factors, depending on the application. In the right environment, an engineered tissue develops. In this process, the combination of cells, scaffolds, and growth factors produce a self-assembling tissue.
Another method is to use an existing scaffold from the collagen in cells of a donor organ. As of 2013, this method has been used to bioengineer heart, liver, lung, and kidney tissues. By using scaffolding from human tissue discarded during surgery, researchers are exploring ways to use a patient's own cells to make customized organs that will not be rejected by the patient's immune system.
Some synthetic biology approaches to tissue engineering include manipulations to genes that code for signaling proteins and other proteins that control the self-organization programs in multicellular organisms during development and regeneration for the purpose of generating self- assembling structures.
A method for construction of self-assembling structures would use the sequence, 1) form a pattern, 2) change gene expression, 3) trigger morphogenesis. Researchers from University of Edinburgh described their construction of a net-like structure by two cell types which formed a pattern, resulting in differential gene expression between the two cell types. The holes in the “net” were formed when a morphogenic effector was used to drive cell death in one cell type.
The SynNotch system developed by Dr. Wendell Lim's lab at UC San Francisco and patented to Cell Design Labs, is also being used for the generation of self-organizing tissue. Lim’s lab used synNotch to program two groups of cells to self-organize into a two-layered sphere. One group of cells expressed a signaling protein on their surfaces and the second group were engineered with a custom synNotch receptor programmed to detect the protein on the surface of the other cells. Neither of the cell types formed structures on their own but when grown together, the first cells activated the other cells to produce cadherin proteins, making them sticky and cluster together. The sticky cells formed a core and the other cells formed the outer layer. In the paper published in Science in 2018, Lim’s group demonstrated self-assembly of multiple tissue patterns and the ability of their spheroids to self-repair when damaged.
