Hydrogels in action: artificial intestines
Discovery News reported last week on an artificial intestine intended to treat short bowel syndrome in children. I thought this was pretty snazzy and looked up the original publication on PubMed.
Tissue engineering, while an exciting field with sexy goals, is fraught with challenges, starting with the scaffold. What scaffold materials can be used that can be implanted in a patient without adverse affects and encourage functional tissue development? What characteristics should the scaffolds have? Hydrogels are useful scaffolds because their physical and mechanical properties resemble soft tissue. A hydrogel also allow water and small molecules to diffuse throughout its structure, allowing nutrients to reach growing tissues. Cells can be encapsulated either within the hydrogel at the time of polymerization, or added to the surface after polymerization; the choice depends on a variety of factors including the application and the type of cells.
The researchers who have developed this artificial intestine employed the principle that replicating the cells’ environment as closely as possible will provide the most functional engineered tissue. One of the challenges in replicating small intestinal structure was to be able to create villi, or fingerlike protrusions from the surface of the intestine. The presence of villi increases the small intestine’s surface area and allows a greater amount of nutrients to be absorbed. The villi are small structures-on the order of millimeters in a human-and conventional molds would either not be able to make the villi small enough or allow the hydrogel to emerge intact from the mold. The researchers solved the problem by making two molds. The first is made of PDMS, a hard polymer with the villi projections. A mold of calcium alginate was cast on the PDMS. The sodium alginate mold is filled with the hydrogel. Once the hydrogel is polymerized, the calcium alginate is dissolved, leaving just the hydrogel with the projections for villi. The villi formed were 400-500 microns (millionths of meters) in height, or 0.4-0.5 millimeters.
Using collagen as their hydrogel of choice, the researchers were able to grow Caco-2 (colon cancer cells) on the hydrogel. The cells were able to grow on the scaffold, and the cells that grew on the projections resembled villi.
Although this model of a human intestine is pretty awesome, I wouldn’t consider artificial intestines to be “near reality”. The Discovery News article states their next step is to grow a larger intestine model (the published data was on a very small scale), and then to implant the intestine in mice. Will the engineered intestine function absorb enough nutrients to sustain a living being? Is it possible to vascularize the newly developed tissue? Will cells from the patient be able to grow as well in the hydrogel as the Caco-2 cells? There are a lot of steps between these experiments and a working intestine for humans.
J.H. Sung et. al. “Microscale 3-D Hydrogel Scaffold for Biomimetic Gastrointestinal (GI) Model” Lab Chip, 2011, 11, 389