Daniel S. Kohane, M.D., Ph.D.

Venous malformations — tissues made up largely of abnormally shaped veins — are often difficult to treat, especially when located in sensitive areas like the eyes, face, and genitourinary organs. In the worst cases, the lesions are disfiguring and can crush or obstruct surrounding tissues, cause bleeding and clotting, interfere with breathing or vision, or impair circulation.

Katie Ladlie, 25, has been there. Her lesions affect various parts of her body, but most seriously her left leg. As a child, she came to the Vascular Anomalies Center at Boston Children’s Hospital from Missouri for multiple treatments. These helped contain some of her smaller lesions, but not so much her worsening left leg, which became enlarged and painful as blood pooled in the abnormal veins and damaged her knee joint. Eventually, she could no longer walk and was out of options. At age 12, wanting to play sports, she opted to have her leg amputated at her home hospital in Missouri. With the use of a prosthesis, this would allow her to be more active and mobile… Continue reading.

Opioids remain a mainstay of treatment for chronic and surgical pain, despite their side effects and risk for addiction and overdose. While conventional local anesthetics block pain very effectively, they wear off quickly and can affect the heart and brain. Now, a study in rats offers up a possible alternative, involving an otherwise lethal pufferfish toxin.

In tiny amounts, in a slow-release formulation that efficiently penetrates nerves, the toxin provided a safe, highly targeted, long-lived nerve block, researchers report today in Nature Communications. The study was led by Daniel Kohane, MD, PhD, director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital… Continue reading.

At TEDMED 2014, Daniel Kohane, Professor of Anesthesia at Harvard Medical School and a Senior Associate in Pediatric Critical Care at Boston Children’s Hospital, revealed some of the amazing work he’s doing with nanoparticle technology to transform the power, safety, and specificity of drugs. 

Imagine being able to treat your medical condition immediately when you need to, safely, and without input from anybody else. No waiting to see your doctor, no wondering whether that extra dose of medicine will be too much.

Sound like magic? Well, that is exactly what many of us scientists in nanomedicine believe is right around the corner. And we are proposing the use of a “wand” to make it happen.

Here’s how it would work in a patient with chronic pain. Such a patient would likely have pain that would wax and wane throughout the course of the day and during the night. His/her need for relief would also fluctuate, depending on activity and effort level. Currently, oral pain pills would generally be used to treat the condition, which would take effect sooner or later, and might or might not make the patient adequately comfortable. In some cases, the medicines could make the patient too comfortable, or effectively stoned. The wand could make all of this so much better.

The wand would actually be a laser, or another powerful light source. The patient would place the laser over the painful area and press a button, firing near-infrared light into the affected tissue, where the patient’s physician had injected or implanted a reservoir of drugs. That reservoir would have been built with light-sensitive nanostructures (like those in my TEDMED talk) so that it would respond to a specific light fired by the laser by releasing those drugs. So, using the wand would cause pain medications to be released at the site where the pain is – and only there; no getting stoned with this treatment. And by varying the intensity and duration of the light beam, the patient would be able to determine exactly how much pain relief is delivered, and for how long.

This approach need not be limited to pain; it could be used for a wide range of diseases, in many parts of the body. And the wand need not use light. Scientists have shown that similar effects can be achieved with oscillating magnetic fields, ultrasound, electricity, and many other energy sources. In fact, people are now looking at drug-releasing devices that would not even require the wand component – there would be indwelling sensors on the device that could sense when a drug needed to be released. Alternatively, the devices could have computerized programming that would enable complex patterns of drug release suitable for a particular disease. That process would remove the burden from the patient of having to self-administer injectable drugs several times a day.

As nanoscience gets increasingly sophisticated, it opens up possibilities for medicines that are specific, targeted, with fewer side effects, and easier to deploy. While the potential is not truly magical, they are certainly parts of this field that previous generations of physicians, scientists, and patients would have thought impossible.

Scientists have developed a technique for constructing silicon nanowire tissue scaffolds that contain nanoscale electrodes capable of monitoring intra- and extracellular function within living biological tissues grown through them. The porous three-dimensional (3D) biocompatible scaffolds can be generated as a mesh or planar construct and manipulated into just about any shape required before seeding with living cells. Embedded in the framework are silicon nanowire field-effect transistor (FET) detectors that can monitor and detect changes in physicochemical parameters within tissues grown through the scaffold. Initial experiments demonstrated utility of the platform to monitor electrical responses in tissues grown from cardiac and neural cells, and also to monitor pH changes in synthetic blood vessels constructed from smooth muscle cells.

The Harvard University and Massachusetts Institute of Technology researchers claim the technology marks the first time that electronics and tissue engineering have been combined at the scale of the structures within the extracellular matrix surrounding cells, and without affecting cell viability or function. And while they say the technology could have numerous applications for sensing in tissues in vitro and potentially in vivo, one of the most obvious initial uses will be as a tool for studying how drug candidates affect different types of tissues grown in physiologically relevant three dimensions. Harvard’s Daniel S. Kohane, M.D., Charles M. Lieber, Ph.D., Bozhi Tian, Ph.D., and colleagues report their work in Nature Materials, in a paper titled “Macroporous nanowire nanoelectronic scaffolds for synthetic tissues.”

The team led by Charles M Lieber, professor of chemistry at Harvard and Daniel Kohane, professor of anaesthesia at the Harvard Medical School, developed a system for creating nano-scale “scaffolds”, which could be seeded with cells that later grew into ‘cyborg’ tissue.

“With this technology, for the first time, we can work at the same scale as the unit of biological system without interrupting it,” said Lieber.

“Ultimately, this is about merging tissue with electronics in a way that it becomes difficult to determine where the tissue ends and the electronics begin,” Lieber said.

“In the body, the autonomic nervous system keeps track of pH, chemistry, oxygen and other factors, and triggers responses as needed,” Kohane explained, according to a Harvard statement.

Using the autonomic nervous system as inspiration, researchers worked in Lieber’s lab at Harvard to build mesh-like networks of nanoscale silicon wires, about 30-80 nanometres in diameter, shaped like flat planes or in a reticular conformation.

“We need to be able to mimic the kind of intrinsic feedback loops the body has evolved in order to maintain fine control at the cellular and tissue level,” said Kohane.

Harvard scientists have created a type of “cyborg” tissue for the first time by embedding a three-dimensional network of functional, biocompatible, nanoscale wires into engineered human tissues.

As described in a paper published Aug. 26 in the journal Nature Materials, a research team led by Charles M. Lieber, the Mark Hyman Jr. Professor of Chemistry at Harvard, and Daniel Kohane, a Harvard Medical School professor in the Department of Anesthesia at Children’s Hospital Boston, developed a system for creating nanoscale “scaffolds” that can be seeded with cells that grow into tissue.

New tissue scaffold could be used for drug development and implantable therapeutic devices.

To control the three-dimensional shape of engineered tissue, researchers grow cells on tiny, sponge-like scaffolds. These devices can be implanted into patients or used in the lab to study tissue responses to potential drugs.

A team of researchers from MIT, Harvard University and Boston Children’s Hospital has now added a new element to tissue scaffolds: electronic sensors. These sensors, made of silicon nanowires, could be used to monitor electrical activity in the tissue surrounding the scaffold, control drug release or screen drug candidates for their effects on the beating of heart tissue.

The research, published online Aug. 26 in Nature Materials, could also pave the way for development of tissue-engineered hearts, says Robert Langer, the David H. Koch Institute Professor at MIT and a senior author of the paper.

“We are very excited about this study,” Langer says. “It brings us one step closer to someday creating a tissue-engineered heart, and it shows how novel nanomaterials can play a role in this field.”

Lead authors of the paper are Bozhi Tian, a former postdoc at MIT and Children’s Hospital; Jia Liu, a Harvard graduate student; and Tal Dvir, a former MIT postdoc. Other senior authors are Daniel Kohane, director of the Laboratory for Biomaterials and Drug Delivery at Children’s Hospital, and Charles Lieber, a Harvard professor of chemistry.

EYES can reveal an awful lot about somebody. Look into someone’s eyes and you can tell if he is happy or sad, truthful or insincere, sober or drunk. By peering deeper still, ophthalmologists are even able to gauge a person’s health, spotting far more than just conditions that affect the eye itself: hypertension and brain tumours can also be diagnosed by examining the retina. Eyes are in many respects windows on the body, even if they are not quite windows on the soul.

And now contact lenses, normally used to bring the outside world into focus, are making it possible to peer back in through these windows. The idea of “smart” contact lenses that can superimpose information on the wearer’s field of view has been around for a while, but contact lenses are also being developed that use embedded sensors and electronics to monitor disease and dispense drugs. Such devices may eventually be able to measure the level of cholesterol or alcohol in your blood and flash up an appropriate warning…

…Another smart contact lens is, however, designed to be worn continuously. Although still under development, this lens is aimed at treating diseases rather than monitoring them. It has been developed by Daniel Kohane, a professor of anaesthesiology and director of the Laboratory for Biomaterials and Drug Delivery at the Children’s Hospital in Boston. His smart lenses are designed to release drugs slowly into the eye over a long period.

Compared with the simplicity of eye drops this may seem a bit over the top, but there are very good reasons to develop this sort of technology, says Dr Kohane. “Eye drops are not very efficient—only a small fraction actually gets into the eye,” he says. “But the bigger problem is compliance.” A common problem with ophthalmic diseases is that patients fail to apply their eye drops as prescribed. “Things that should work don’t work, and that leads to an escalation of the disease and the therapy.”

Whether it’s a headache or a sore knee, a toothache or a strep throat, people are used to taking their medicine in pill form. But to scientists, such drugs can be hard to swallow because the pill is a blunt tool: As it wends its way through the body, such medication may wreak side effects or fail to make it to its intended destination efficiently.

Now, with implantable pumps, tiny particles of drug, and novel materials that can release medication at a controlled rate, researchers are experimenting with new channels to deliver drugs directly to areas of the body where they can be most effective…

…Dr. Daniel Kohane, director of the laboratory for drug delivery and biomaterials in the anesthesiology department at Children’s Hospital Boston, has been working with scientists at Massachusetts Eye and Ear Infirmary to develop technology that could replace a complicated drop regimen with a contact lens.

To explain how it works, Kohane uses food metaphors, comparing the drug-eluting contact lens to a pita pocket with drug stowed inside.

“The pita bread is the contact lens material, and inside we slide a doughnut of polymer with a drug in it,’’ Kohane said.

A drug could be continuously delivered to the eye through the contact lens, with a closely controlled dosage.