Whether due to disease, injury or other causes, millions of Americans suffer tissue loss or organ failure every year. Those who need replacements are put on organ donor lists. But the supply falls far short of demand.
To supplement the low numbers of donors, scientists during the past two decades have attempted to grow human organs in laboratories. While they have had limited success with skin and other simple tissues, they have encountered many challenges in producing complicated organs, such as the liver, kidney and lung.
Part of the difficulty is that those organs require an intricate network of blood vessels to support their growth. Such vascular systems bring oxygen and nutrients to the tissue and carry away waste. Unlike in the human body, tissues grown in the laboratory do not necessarily generate their own vascular supply, says Jeffrey Borenstein, director of the biomedical engineering center at Draper Laboratory in Boston.
“There’s only so much of a distance that the oxygen and nutrients and waste can travel, so you need to have not just a few large blood vessels, but this incredible network of blood vessels that goes down to the capillary level,” he says.
Most of the work in tissue engineering has focused on the biology of the cells and the material properties of the “scaffold” that the cells thrive on. Just as the walls of a house need a foundation upon which to rise, the cells of tissues require a frame upon which to grow.
“If you just grow the cells in a dish, you’re going to have an amorphous blob of cells that do not have much mechanical integrity or stability, and that do not take a very defined shape,” says Borenstein.
Conventional tissue grids lack sufficient structures to support a sophisticated vascular system. By addressing the engineering of the scaffold itself, Borenstein and his team have taken a novel approach to the vascularization problem.
Using processes and tools commonly employed to manufacture small electronics, known as micro-electromechanical systems, or MEMS, the researchers are micromachining minuscule scaffolds made of biodegradable or bio-absorbable polymers with tiny channels in which vascular cells can attach and multiply. Once the blood vessel network is viable, the scientists can spur the growth of tissues and organs around it.
“Our hypothesis is that you need to create a microenvironment that the cells experience in the body. You need to recreate that in the lab, and microtechnology is the way to do that,” says Borenstein.
At Draper’s MEMS laboratory, scientists typically work with silicon materials to produce tiny sensors for automotives and guided munitions. Borenstein has amended the microfabrication process slightly to engineer the tissue scaffold devices. After creating a master mold of the scaffold on a silicon wafer, scientists cast replicas in thin films of polymer. Five to 35 layers of the polymer are then bonded and stacked to form a flexible, three-dimensional system of transparent tubes and connections. Scientists finally culture cells in the system and begin growing tissue.
“We’re really bringing in novel engineering tools to help solve the problem,” says Borenstein, whose work is sponsored by the Center for Integration of Medicine and Innovative Technology, a consortium of teaching hospitals, engineering schools and research laboratories in Boston. Formed 10 years ago, the organization is overseen by the Army’s Telemedicine and Advanced Technology Research Center at Fort Detrick, Md.
So far, the scientists have grown kidney, liver and lung tissues in the lab. Many of the organs have been implanted into large animals for long-term experiments and studies.
Researchers are seeing improved function over what would be done in a conventional cell culture dish, says Borenstein.
The goal is to grow full organ replacements for human patients. “I still think that’s 15 to 20 years away, but the day will come,” he says. “Really difficult organs like the liver and kidney may take that long, but there will be advances in the meantime,” he says.
In the interim, the technology could help improve organ-assist devices already on the market, such as kidney dialysis machines. These devices filter body fluids through a variety of artificial processes designed to mimic the functions of a particular organ. Borenstein’s research will make it possible for the devices to filter fluids in a more physiological manner. Because the blood vessel network built by the scientists is similar to those found in organs, blood, for example, would flow through the devices in a pattern similar to pathways found in the body.
The technology would be a particular boon to patients with liver failure, because the industry currently lacks a liver-assist device, he says.
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