BOSTON, Mass. (Ivanhoe Newswire) - It's a lab like no other, and some day what's happening inside it could change or even save your life. Right now a big group of doctors and scientists are creating what could be medicine's next big thing or things.
Geckos may make you think of TV ads, but inside a lab the little lizards' feet are the inspiration for this innovation, a nanoscale adhesive
"That can almost serve as like a duct tape or like a band aid but for internal procedures," Jeffrey M. Karp, Ph.D., assistant professor in medicine and health sciences and technology at Harvard Medical School, laboratory for advanced biomaterials and stem-cell-based therapeutics at Brigham & Women's Hospital, told Ivanhoe.
It could be used after a variety of surgeries to prevent leaking or bleeding and to heal hearts after a heart attack. Chemical and bioengineer doctor Jeffrey Karp runs the KarpLab.
"We have chemists, material scientists and immunologists," Dr. Karp said.
While a lot of labs focus on a particular technology or disease, here, they're tackling a ton. Inspired by oil drilling, a needle with a clutch, so it never overshoots its mark. A gel is designed to be injected into an arthritic joint and wait to attack pain.
"And only in the presence of inflammation, when there's lots of enzymes that are secreted this gel will then disassemble and release the payload," Dr. Karp said.
The gel could also be used to prevent brain tumors from re-growing. A nanoparticle cream could help you cope with a nickel allergy. The doctor is one of millions who suffer from it. Just rub it into your skin.
A small sampling of the work this dedicated team is doing right now to make your life better and maybe longer.
Money from the American Heart Association and the Brain Science Foundation helped pay for some of the research at the lab. Doctor Karp tells us the nickel allergy cream could be available to the public within a few years. Some of the other devices and technologies could take a lot longer to hit the market.
ABOUT NANOTECHNOLOGY: Nanotechnology is science at the size of individual atoms and molecules: objects and devices measuring mere billionths of a meter, smaller than a red blood cell. At that size scale, materials have different chemical and physical properties than those of the same materials in bulk, because quantum mechanics is more important. For example, carbon atoms can conduct electricity and are stronger than steel when woven into hollow microscopic threads. Nanoparticles are already widely used in certain commercial consumer products, such as suntan lotions, "age-defying" make-up, and self-cleaning windows that shed dirt when it rains. One company manufactures a nanocrystal wound dressing with built-in antibiotic and anti-inflammatory properties. On the horizon is toothpaste that coats, protects and repairs damaged enamel, as well as self-cleaning shoes that never need polishing. Nanoparticles are also used as additives in building materials to strengthen the walls of any given structure, and to create tough, durable, yet lightweight fabrics.
GECKO TO THE RESCUE: Geckos can scale smooth walls at a whopping three feet per second, and in last decade scientists have begun to understand how these little lizards can defy gravity. It turns out that gecko feet have millions of little projections, called setae, which split into hundreds of projections shaped like spatulas. Each of these tips can attach to smooth surfaces by taking advantage of intermolecular forces, which are individually relatively weak and unstable but can combine to generate enough force to allow a gecko to hang upside-down from one foot.
Professor Jeff Karp, an investigator in the Harvard-MIT Health Sciences and Technology program and his collaborators had made a new polymer called poly(glycerol-co-sebacate acrylate), created a mold for the polymer using the same processes that are used to make computer chips, utilized some tricks to make the polymer biodegradable and nearly invisible to the immune system, and tested these nifty band-aids on pig intestine in the lab and in the peritoneal cavity of live rats. Since the gecko-inspired adhesive does not require repeated re-alignment of the tissue being patched together, it can reduce the time a patient spends in surgery. Additionally, it can be utilized to connect pieces of the colon in patients with Crohn's disease, or to patch lungs without worrying about air leaks, or even to deliver drugs to parts of a heart that might have died after a heart attack. If all goes well, this bio-inspired adhesive will be found in a hospital near you in less than five years. (Source: karplab.net, MIT)
Dr. Jeff Karp, co-director of the Center for Regenerative Therapeutics at the Brigham's Women's Hospital, talks about how his lab is working on a variety of new medical technologies and what that could mean for patients in the future.
So tell us about this lab, it's got your name on it. What do you guys do here?
Dr. Karp: We develop platform technologies to try to solve big, unmet medical needs. To achieve this I have assembled a team of people in my laboratory with very diverse expertise and experience. We have a chemist, we have a material scientist, an Immunologist, a basic biologist, and we also have a cardiovascular surgeon and a gastrointestinal surgeon. We try to work together to solve medical problems.
What kind of things are you working on right now?
Dr. Karp: Sure. So we work on a variety of different technologies, mostly under the areas of medical adhesives, drug delivery devices, diagnostics, medical devices, and we also do a lot of work in the area of cell therapy.
Do most labs diversify that much when they are trying to solve problems? It seems like a lot.
D. Karp: Right. I think a lot of laboratories focus on a particular technology or a particular disease area. Because of the desire to develop platform technologies, which we can apply to multiple medical problems, we've chosen not to focus on any particular technology or any particular medical problem but instead try to develop technologies that can be rapidly translated to the clinic to potentially address a lot of unmet medical needs.
Can you describe platform technologies?
Dr. Karp: A platform technology is a technology that can address multiple challenges from a diverse set of medical problems.
What's it like having so many things going on in a lab at once. Does it make it more difficult or do you think it kind of helps in the process?
Dr. Karp: I think having a multi-disciplinary lab with people from all sorts of different backgrounds and with different expertise really can help. It's amazing because people with different expertise are able to come together and I think innovation really happens at the interface of disciplines. So by populating the lab with people from different backgrounds, I think that fuels the innovation in the lab and increases our chances of developing technologies that can be rapidly translated to the clinic.
We are very passionate about developing technologies not just for the sake of developing the technologies, but actually trying to bridge the technology with an unmet medical need. By doing so, we try to get these technologies towards clinical translation as quickly as possible. So what we really like to do is align with a clinician who is treating the ailment that we're trying to solve and the idea there is that the clinician can provide critical feedback and design criteria that can help us to develop technology that will have the appropriate parameters so we can quickly translate that to the clinic.
Is that how you determine the problems you want to solve?
Dr. Karp: Right. In biomedical research it's fairly easy to develop new technologies and it's also fairly easy to identify problems, but I think the biggest challenge is trying to bridge the right technology with the right problem. Where we really focus most of our efforts is trying to connect the technology to the problem and if we can do that, there's a well-defined model that we can test these technologies in. It enhances our chance to rapidly translate these technologies to the clinic.
What's the next big thing that we might be seeing?
Dr. Karp: So we develop a variety of technologies. One technology in particular is in the area of drug delivery. I think one of the greatest challenges in drug delivery is the ability to target drugs to specific locations in the body. The standard way of administering a drug is in the form of a pill. Now the challenge with that is the drug that's in that pill will encounter many barriers. The goal is to get the concentration of the drug at the target site into the therapeutic range where it can actually be effective, but the drug must bypass the harsh conditions of the stomach, for example, and be delivered in the intestine and then in the intestine the drug will then go immediately to the liver where a lot of drugs will be metabolized. So you actually have to bypass the activities of the liver in order to get that drug in the right concentration within the bloodstream and a lot of drugs have actually failed or been taken off the market because of systemic toxicity. Because of all of these barriers, the concentration of the drug needs to be quite higher and the quantity of the drug needs to be quite high in the pill. So drugs like Bionx or Bextra which reached multibillion dollar markets had to be removed from the market because of systemic toxicity. Our approach is to develop a localized controlled drug delivery system where we've created a hydro gel. This is a very soft material where we can attract high concentrations of potentially any drug and this can be locally injected into the joint. The novel aspect of this technology is that the gel will remain stable during periods of remission and only in the presence of inflammation when there's lots of enzymes that are secreted, this gel will then disassemble and release the payload.
So it pretty much times itself.
Dr. Karp: Right. We've developed this hydro gel technology so that it will only release drugs in response to inflammation. We've tested this on synovial fluid from human arthritic patients which shows that this does indeed disassemble in the presence of the enzymes within the synovial fluid. We've also injected this into animal models and showed that it can remain stable for several months in normal tissue. We're also in the process of gearing up to test this in more preclinical models and hopefully will be able to enter clinical trials in the next few years.
Is this specifically for arthritic patients?
Dr. Karp: Right. In addition to arthritis, we've also been exploring the potential of this technology in a wide variety of other applications. In particular, we think that it has desirable properties that may make it suitable for a treatment of tumors and have been investigating whether we can use this to prevent recurrence of brain tumors. We have a grant from The Brain Science Foundation to see if we can inject this gel into brain tissue following the resection of a tumor and the goal is to try to prevent the tumor recurrence. In particular we're focused on glioblastoma, which is one of the most deadly forms of cancer.
What kind of medication would be in there? Something to prevent the tumor from regrowing?
Dr. Karp: Right. We found some novel ways to make anticancer drugs more toxic, but the gels that we're using are able to protect those drugs until cancer cells arrive and start secreting enzymes. The idea is that we potentially could inject this gel throughout the brain and only when the tumor cells activate and start becoming invasive will the gel disassemble and locally release the chemotherapeutic to kill those cancer cells so that we can prolong the life of the patient and hopefully prevent recurrence.
Are those the two main things that this gel can be used for?
Dr. Karp: We're also investigating other potential uses of this gel. We think in addition to inflammatory arthritis, this gel may also be very interesting in treatment of osteoarthritis. The gel may provide lubricant properties that may slow down the progression of the degenerative disease of osteoarthritis.
Can you tell us about the Nano scale adhesive?
Dr. Karp: There's a big unmet medical need to develop better adhesives that can either replace sutures or augment sutures. So we've been developing tape based medical adhesives that can almost serve as like a duck-tape or a band-aide but for internal procedures. We make these from materials that we synthesize in the laboratory that are fully degradable. They are also very elastic so we can stretch these 400 or 500 percent over many cycles. We're developing these adhesives that can be applied potentially to the gut following gastric bypass procedure, which is a treatment for obesity where a segment of the intestine is severed and then reconnected. The challenge there is that if the sutures are too tight this can cause necrosis and leak a fluid, or if the sutures are too loose this can actually leak fluid as well which can be fairly catastrophic. The idea is that we may be able to replace sutures or augment sutures in this application to prevent these leaks from occurring. We're also interested to apply this to the lungs following lung resection procedures where about 50 percent of patients have extended hospital stay because of error leaks. We are also in the process of developing through a grant from The American Heart Association an adhesive patch that can affix to the heart and because these materials are elastic, they can expand and contract as the heart beats. Following myocardial infarction or heart attack, there's a segment of the heart that is no longer functional; it's essentially dead and just scar tissue. The challenge is that over time the heart tries to compensate for this and so the heart will keep expanding and many patients end up going into heart failure and dying as a result. What we're interested in doing is developing an adhesive patch that can affix to the heart and locally release drugs that can stimulate the cells within the heart, the stem cells or the progenitor cells, to migrate into that dead or ischemic tissue to promote regeneration. All therapies right now in the clinic focus on modulating the hemodynamics, so just the blood flow, and there are no current therapies to regenerate damaged tissue in the heart.
What is it like for you taking part in all this different research that really changes lives?
Dr. Karp: I think for us what's most important is that we develop relevant technologies that can rapidly get to the clinic and start helping patients and improving quality of life. That's what really drives us day in and day out.
And the adhesive is based on something pretty interesting.
Dr. Karp: So often in the development of medical technologies to solve medical problems we encounter many barriers and major hurdles. So what we like to do is turn to nature because evolution really is the best problem solver. We've been very inspired by creatures like the gecko that's able to walk up walls and hang from a single toe. The mechanism through which the gecko is able to adhere to these vertical surfaces was recently elucidated in the past ten years or so, and as it turns out, there's no glue on the surface of their toes, there's no suction cups. It's purely a physical interaction where the gecko has these hierarchical structures on the surface of their toes and if you look at their toes, they have these lamellar structures that are about the same length scale as our fingerprints. If you look with an electron microscope, it's a very powerful microscope, you see that these are made up of hairs and at an even higher magnification these are made up of these Nano pillars. It's estimated that on the surface of some geckos' toes, if you count up all of those Nano structures, there's over one billion; so these are highly densely packed structures. We've been mimicking creatures like the gecko to try to overcome some of the challenges in developing medical adhesives that can effectively apply to tissue.
Can we talk about the Nickel allergy cream?
Dr. Karp: OK. So, it's really amazing to think that 10 to 15 percent of the population suffers from a nickel allergy. Nickel exists in belt buckles, watches, jewelry, cell phones, and coins, so you can imagine the number of people that are affected by nickel allergies, coming into contact with nickel quite often. There's really nothing that has been developed to prevent these allergic reactions. What happens is that patients who have nickel induced contact dermatitis, when they come in contact with nickel, their skin turns red and this can really be debilitating in many cases. There's been an effort to try to develop barrier creams that can prevent the nickel from penetrating into the skin and causing these toxic responses, but the challenge is that most of these are either not affective or they actually will penetrate into the skin and induce toxicity. So we looked at the generally recognized safe list by FDA, a list of agents that are referred to as safe, that have been in food products for years and years. We found some agents on that list that could bind to nickel with great affinity and so we took a formulation of those safe agents that were on the Nano scale. These are Nano particles but we insured that these were too big to fit into through the skin, so the Nano particles remained on the surface of the skin but were still very small. One of the really important features of Nano scale materials is that they have very high surface areas to volume ratios. The idea was that if we could put these particles that could bind nickel with really high affinity in the form of a cream and apply it to the skin, then when it came in contact with nickel, it would be able to catch the nickel and prevent it from penetrating into the skin. We were able to show that the Nano particles that could strongly bind nickel could do so in the presence of artificial sweat, which is important to do because sweat can actually accelerate the release of nickel from metal objects. We demonstrated that we could achieve the order of a 100 to 1,000 fold decrease in the nickel penetration into skin through using this approach. We also showed that in an animal model we could prevent the toxic response of nickel to nickel sensitized animals.
Have you used it on yourself yet to see if it works? Or has it not made it that far yet?
Dr. Karp: I have tried it on myself and it does appear to work very well. Although it's just a man of one and what we are doing now is trying to pull together a team of people who can help consider commercialization avenues; how can we actually get this into the hands of the people who need it the most.
How long until that happens?
Dr. Karp: We think that this technology in particular can reach the market in a very short time. It could be within a year or two.
What happens when you get that allergic reaction?
Dr. Karp: A lot of people are sensitized, especially women when they get their ears pierced may be sensitized, and then you're sensitized for life. So when you come in contact with nickel and you have developed the sensitization, the skin will turn very red, start to crack, and it's a burning, itching feeling. It can really cause a lot of discomfort.
When you get it personally though, how does it feel?
Dr. Karp: You just can't stop itching. I mean, you just can't stop scratching the red areas. It's crazy.
How about cell therapy.
Dr. Karp: OK. I think we're getting to a point now in cell therapy where we can obtain almost any cell type in the body in unlimited quantities, with a couple of exceptions. The big challenge is really, how do you get those cells to the right site in the body and then have those cells graft and survive for long periods of time to perform their functions? When we take cells and manipulate them outside the body and then transplant them, most of the cells will die; so that's a big challenge. Also, these cells are at the mercy of the biological micro environment wherever they end up so if they end up in different places in the body, they may actually have completely different properties. We've been developing a series of technologies that can control where the cells go following administration. For example, just like in your car where you may have a GPS and you program in the address, we know the zip code of blood vessels in different tissues. We've developed a technology where we can program the address on the surface of cells prior to transplantation and we can enhance or have those cells concentrate on particular tissues following simple intravenous infusion.
You just put them in the arm and they know exactly where to go?
Dr. Karp: Right. Not all of the cells will get to the desired location but we've shown in a number of studies that we can significantly increase the number of cells that get to target sites following intravenous infusion.
What cell therapy is this used for?
Dr. Karp: The major cell therapy that people are probably the most familiar with is bone marrow transplantation, or core blood transplantation, or peripheral blood stem cell transfer, where the cell type which is responsible is called the hematicoletic stem cell and this is a cell that can form all the cell types in the blood. Despite the great success of this approach, over 50 percent of patients get graft versus host disease, where cells such as T cells within the graft can actually attack the host. This is really a major challenge in cell therapy. Cell therapy offers hope for a variety of medical conditions. One example would be trying to treat ischemic tissue in the heart following a heart attack and so if you can repopulate the cells in the heart, which are called cardiomiosites, within those damaged regions, there may be potential to then regenerate the heart and prevent patients from developing heart failure.
With this technology how did you even start, it seems very complicated to find that zip code?
Dr. Karp: A lot of the basic biology has been worked out, over many decades, of what is expressed on the surface of blood vessels. Through knowing the different properties of blood vessels in different tissues, we're able to then engineer cells that can target those specific tissues with great precision.
They are to help rebuild it?
Dr. Karp: Right. Cells can offer a variety of potential and great opportunity for solving a lot of medical problems. In particular, cells can be used to promote angiogenesis, which is new blood vessel formation, and new blood vessels are useful to treat ischemic tissues. That could be used to treat the heart following a heart attack; it could be used to help peripheral vascular disease which is often in the limbs, and a variety of other medical conditions. The cells can also secrete factors that can down regulate inflammation. So instead of taking a pill, an anti-inflammatory drug for example, you can actually get cells to express in high concentrations anti-inflammatory agents. The benefit is that the cells are not just secreting one anti-inflammatory agent, they're actually secreting a variety of anti-inflammatory agents that can work together synergistically to provide a potentially better response. Cells also offer the opportunity to regenerate tissues. The cells can differentiate or become very specific cells types in the body that can then form tissues such as bone, fat, cartilage, muscle and other tissues to promote regeneration.
Could this be used in a drug delivery system as well?
Dr. Karp: Absolutely. In addition to modifying cells to control where they go, we've been interested in actually controlling the fate and function of the cells following transplantation. We developed a technology where we can equip cells outside the body with small devices that we call degradable micro particles. These particles are then closely associated with every single cell that we transplant. So following transplantation we actually can potentially exhibit control over every single cell because they all contain these bioengineered micro-particle devices that will release agents to the cell for weeks, and potentially months.
How about the cell surfaces sensor?
Dr. Karp: One of the greatest challenges in cell therapy is trying to understand after you transplant cells, what those cells are actually doing and have those cells become different types of cells or are they actually the same cell that you delivered. Right now we only have technologies that can tell us where the cells are in the body, but they don't provide any other information besides that. So we've been developing technologies where we can actually immobilize sensors on the surface of cells. These are sensors that enable us to monitor the cells following transplantation and we're in the process of developing this technology to work in various sites in the body so we can explore biology with potentially unprecedented spacial and temporal resolution, which will provide greater avenues for future of cell therapy.
How far down the pipe is that?
Dr. Karp: We've demonstrated that these cell surface sensors can work really well within a petri dish within the laboratory. We've also infused these into the body, into the bloodstream, and showed that the sensors don't impact the ability of the cells to travel through blood vessels and hone to specific tissues. Now we're in the process of developing these sensors to work in vivo. So we hope within the next year or two to have that up and working.
FOR MORE INFORMATION, PLEASE CONTACT:
Jeffrey M. Karp, PhD
Laboratory for Advanced Biomaterials and Stem-Cell-Based Therapeutics
Brigham & Women's Hospital