A Defense from Your Natural Defenses
By Cindy Moffett
The young science of neuroprosthetics may one day relieve many human miseries. Sensors implanted in the brain, for instance, promise to translate thought into motion for artificial arms, legs, and hands. Since the mid 1980s, experimental successes include implanted electrodes that collect information from neurons and then send it to a computer, making it possible for quadriplegics to move a computer cursor and a robotic arm.
Moving beyond experimental settings, however, means extending the life of sensors. When a sensor is implanted in a living organism, the organism—quite reasonably—sees the sensor as a foreign body. The invader is walled off with a protein coat, and the surrounding damaged tissue is repaired. This repair causes scarring, however, which prevents the sensors from gathering data from nearby neurons. Within months (or even days), the sensors become useless.
Finding a way to keep sensors working drives a range of biomedical research. Assistant Professor Wei He of the College of Engineering thinks that anti-inflammatory drugs might be a key. If tissue does not become chronically inflamed, repair cells will not be instructed to wall off the sensor. She is working to create polymers that will carry an anti-inflammatory drug to keep scar tissue from forming.
“I use the analogy of a shuttle detaching from a spaceship,” He says. “The drug-containing component is the shuttle that floats around the ship, which is the implanted neural sensor. The material is designed to keep the drug confined near the sensor, so the local tissue will be treated. We don’t want the drug-containing component stuck on the sensor, as this will interfere with the device’s sensing capability.”
By controlling the size or the chemical properties of the “shuttle” molecule, He can control how far the drug travels before it acts.
He also hopes to correlate the timing and amount of drug release with tissue response. If the drug were only released when needed—when chronic inflammation occurs—then it would be far more effective at inhibiting scarring, and the tissue wouldn’t be flooded with unneeded drugs. One trigger she’s working with is pH, a measure of acidity or alkalinity. Decreased pH (that is, increased acidity) means inflammation, so the polymer will respond to lower pH by releasing the drug. Although pH-sensing drug release has been widely explored in cancer research, it has not been explored in neuron interfaces.
Other hallmarks of chronic inflammation include the buildup of oxidative substances, such as hydrogen peroxides. Theoretically, one could use these oxidative molecules as triggers for drug release by linking the drug molecules to a carrier through chemical bonds that can be broken by oxidants.
“Essentially, this strategy can be viewed as a more personalized, patient-specific treatment,” says He. “We are taking advantage of the various markers associated with the tissue response to implants and using them to our benefit to control the drug release. The key is to create a safe and trigger-responsive drug deposit around the implant.”
He’s doctorate is in chemistry, but her research has progressed from chemistry to engineering materials to biomedical science. “It is amazing to incorporate biology and engage in such an interdisciplinary field. Materials interfacing with cells is the best of both worlds to me,” she says.
In 2002, she helped develop a family of polymers based on a compound used to enable surface patterning for directed cell growth. The polymers she is currently creating and testing are part of the same materials family, but keyed to drug delivery.
Investigating each polymer is a long process that begins with seeing how well living cells tolerate a material in a dish.
“We feed the materials to the cells. Then we put them in a nice, warm environment, with the temperature of the human body, to grow,” she says.
One day’s microscope results are displayed on a computer screen in her laboratory. Some of the cells look like two joined circles, and others look like four joined circles. “They are growing normally so far, judging by their appearance. We’ll run biological tests to quantify how many cells are alive,” says He. “Tomorrow we’ll repeat the culture and change the feed to other materials and see how well it does.”
Once she determines that a material is not toxic to the living cells, she sees how well it works to carry a drug. “We connect the anti-inflammatory drug to a polymer. Is it still anti-inflammatory when it’s on the material? Will the drug remain bioactive after going through the chemical reaction?”
Theoretically, these tests proceed quickly. Practically, however, there are new issues with each material.
“For example, the number of drug molecules attached may be less than we expected, or the solubility of the final product may be too low to warrant further application,” says He. “It can take weeks, months, even years to find a solution that works.”
Once successful at the cellular level, He will conduct an approved animal trial, most likely with a healthy rat. “If that’s effective, we’ll try to emulate the response in larger animals. At every stage, we’re determining if the response is acceptable and the long-term performance of the implants is improved.”
He recently won a prestigious Faculty Early Career Development (CAREER) award front the National Science Foundation, which funds her work for five years.
“This award lets me recruit the best of the best students to work with me,” she says.
The strongest power behind her research, however, may be her hopes for the future.
“In a perfect world, I hope my work will extend the longevity for neural implants. I hope it will also apply to other implant/host responses,” He says. “There’s been a longstanding problem with glucose sensors for diabetics, for instance. Other implantable sensors that could benefit from this research include those for treatments of epilepsy and other debilitating neurological disorders. Adverse inflammatory responses plague all sorts of indwelling medical implants and devices. A better understanding of the host response will enable us to engineer a more effective solution to manage the response for our benefit.”Tags: Biomechanics • Biomedical Engineering • Materials Science and Engineering • Polymers • Wei He