Building Organs, Like Houses, Depends on the Foundation

Imagine a world where people aren't suffering and dieing while waiting for an organ that they have to spend the rest of the life protecting from rejection. This is a world that tissue engineers and researchers are determined to make a reality. It seems that the extracellular matrix (ECM), once thought as no more than a 3D structural foundation, might be the key.

One of the main obstacles to growing a transplantable organ is having the proper cell grow, in the proper location, with the proper alignment with its neighbors. The ECM (pictured right) is a nanostructure where morphogenesis, differentiation, proliferation, adhesion and migration of cells are determined. The cells adhere to the ECM and the ECM's topography, mechanical properties, and immobilized growth factors can all deliver important cues to the cell. The natural ECM is made of collagen and elastins, but scientist hope to recreate them by using nanofibers. These nanofibers would be woven to create the 3D structure of the organ, but the important aspect of these fibers would be what was done to them.

The first aspect of the nanofibers to be altered would be their topography. It seems that the surface of the fiber can have an important role in cell differentiation and morphogenesis. Different tissues, be they cardiac or liver, require different types of scaffold with different nanotopography (see below). Scientists have grown a 2 dimensional cardiac muscle using this technique that resulted in cardiac muscle that could produce an aligned contraction. This technique has not been able to be Incorporated into a 3D scaffold as of yet but controlling the alignment of cells is an important step to organ development.

The next aspect of the fibers to be modified allows the ECM to release instructive cues to the cells. The delivery of certain molecules, like cytokines or growth factors, are vital to the viability and functionality of tissue whether they be in the body or an in vitro 3D scaffold. One possible way to give the cells the cues they need is by the use of gold nanowires. These wires can be functionalized with certain biomolecules and maneuvered around the 3D scaffold using electric fields. Once in the proper location this wire would release its contents and the cells in that location would get the desired cues needed to differentiate into the needed cells at that location.

This research shows that the ECM scaffold of an artificially grown organ is a lot more important than just giving the organ it's overall shape. It determines what cells grow were and whether those cells will even be able to function as a tissue. It seems that organs, like buildings, depend a lot on their foundation.

Article: http://www.nature.com/nnano/journal/v6/n1/full/nnano.2010.246.html