The 3D Challenge

The biggest challenge in tissue engineering is the 3D nature of the enterprise. There is only one tissue which is essentially 2D, skin, which exists in a sheet-like form; and tissue-engineered skin is already commercially-available and approved for use. So why is 3D such a problem? 3D is a problem because it makes growth of the tissue ex vivo, that is, outside the body, much more complicated. If you have a 2D structure everything is exposed, whereas by creating a 3D structure you automatically create the distinction between what is “inside” vs. “outside”.

Studies have shown that simply placing cells on a 3D structure changes which genes are expressed versus just plating them on a 2D plane. Additionally, in order for cells to survive they need to constantly receive nutrients from the outside and get rid of waste products. This is the purpose of blood vessels (vasculature) in the body. In culture in a dish in the lab, or in a newly transplanted synthetic material, however, there are no blood vessels. In these instances nutrient exchange occurs by diffusion. Diffusion is very easy from a 2D surface, but much more complex from a 3D structure. In a 3D structure, cells on the outer surface behave as if they were on a 2D plane, and are uniformly exposed to the outside, whereas cells on the inside rapidly deteriorate in terms of viability and functional capacity the further away from the surface they are. Once blood vessels enter the transplant, however, nutrient exchange becomes uniform throughout, and the distinction between inside and outside increases.

Think, for example, of a loaf of bread. Loaves can be very hard and crusty on the outside, where they are in direct contact with hot air, but the inside of the loaf can still be airy and light because it has been sheltered by the outer crust. The result is a loaf of bread with very different outside versus inside, although all the dough was uniform prior to baking. Similar concepts apply to tissue engineering of bone, where often, in the literature, one can find the production of a hard bony exterior to the scaffold, while the inside is airy and empty, due to different conditions experience by the transplant even though the original components were the same throughout. Unlike bread, however, we want our transplant to be uniformly boney, instead of an empty center. The empty center occurs when cells on the inside don’t have blood vessels and hence they die through lack of nutrient exchange. The goal of my PhD is to increase the rate of blood vessel formation and ingrowth into the scaffold to make a transplant that is uniformly boney. A loaf full of crust.

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