Make Organs Using Composite Scaffolding

Daniel Eberli, Luiz Freitas Filho, Anthony Atala, James J. Yoo, Composite scaffolds for the engineering of hollow organs and tissues, Methods, Volume 47, Issue 2, Tissue Engineering, February 2009, Pages 109-115, ISSN 1046-2023, DOI: 10.1016/j.ymeth.2008.10.014.

(http://www.sciencedirect.com/science/article/B6WN5-4TRY3DD-4/2/87bc0603fb427e82f4044dd21095b732)

Organ engineering often requires a scaffold on which to place cells that will eventually populate the structure. There are many requirements for a successful scaffold.

The main criterion for scaffolding material is biocompatibility--does this material cause an immune reaction, does it poison the recipient, does it allow cell attachment etc. A second requirement is biodegradability. Usually, the scaffold needs to survive long enough to guide the cells into a physical pattern but afterwards, it needs to dissolve or degrade away because it would otherwise interfere with cell growth. In addition there are also properties specific to the application such as tensile strength or stiffness.

The materials currently available fall into two categories, synthetic or natural. Synthetic scaffolds are usually made from polymers such as polyglycolic acid(PGA) or polylactic acid(PLA). They have the advantage of being stronger and more uniform than natural materials, and since they are synthetic, they can be mass produced. Natural materials are often acellular matricies. One example used in this paper is a bladder membrane that was washed multiple times to get rid of any cells. The remains consist of mostly collagen and other fibers. Acellular matricies have the advantage of biocompatibility, they may contain adhesion domain sequences and biomimetic factors that promote tissue development.

Since organs are composed of many tissues, it makes sense that the scaffolding should be created to accommodate such a structure. For example, in the case of bladder tissue, there is an epithelial layer that prevents collagen from spilling into the lumen and there is a muscle layer to give it rigidity.

The researchers of this paper decided to make a composite material composed of PGA on one side and acellular bladder tissue on the other. The two layers were bonded with collagen stitching. Muscle cells were seeded on one side and epithelial on the other. The same was done with a pure acellular bladder matrix(ABM) and a pure PGA material for comparison.

The scaffolds were implanted into athymic mice to evaluate them in vivo. Results show that all three showed cell growth. However, the PGA only construct shows less distinct layering of cells and the ABM construct shows a thin muscle layer. In contrast, the composite material showed distinct 3 layer architecture and a thick muscle layer. Certainly this seems to suggest that a composite material is superior but it is not yet clear what factor is affecting layering or muscle cell growth. The paper claims the composite forms a "barrier" that allows well defined layer. However, what this means is not clear. Mechanical testing was done to compare the composite with native bladder but not with PGA or ABM. It is possible that the stiffness might have been an important factor.