Inside a bony structure that spirals like a snail shell in a human’s inner ear, roughly 15,000 “hair” cells receive, translate, and then ship sound signals to the brain. Damage to these cells from excessive noise, chronic infections, antibiotics, certain drugs, or the simple passing of time can lead to irreparable hearing loss.
Harvard Stem Cell Institute (HSCI) researchers at Brigham and Women’s Hospital (BWH) and Massachusetts Eye and Ear Infirmary and colleagues from Massachusetts Institute of Technology (MIT) have developed an approach to replace damaged sound-sensing hair cells, which eventually may lead to therapies for people who live with disabling hearing loss.
In a recent Cell Reports study, the researchers identified a small molecule cocktail that increased the population of cells responsible for generating hair cells in the inner ear. Unlike hair on the human head, the hair cells lining that bony structure, called the cochlea, do not regenerate.
HSCI principal faculty Jeff Karp, HSCI affiliate faculty Albert Edge, and MIT’s Robert Langer were co-corresponding authors of the study. Will McLean, a postdoctoral fellow in the Edge lab, and Xiaolei Yin, an instructor in medicine at BWH, were co-first authors.
In 2012, Edge and colleagues identified a population of stem cells, characterized by an Lgr5+ marker, which scientists could turn into hair cells in a dish. A year later, Edge had converted the resident population of these cells in mice into hair cells, though the ability to restore hearing using this approach has been limited.
“The problem is the cochlea is so small and there are so few cells” that it creates a bottleneck limiting the number and types of experiments researchers could perform, said Edge, director of the Tillotson Cell Biology Unit at Mass. Eye and Ear and a professor of otolaryngology at Harvard Medical School (HMS).
However, by exposing Lgr5+ cells isolated from the cochlea of mice to the small molecule cocktail, the researchers were able to create a 2,000-fold increase in the number of stem cells.
“Those molecules were a key to unlocking this regenerative capability,” said Karp, who is also a bioengineer at BWH and an associate professor of medicine at HMS....
Solving medical problems is extremely challenging. By bringing experts from multiple disciplines together to work at the interface of those disciplines, researchers at Brigham and Women’s Hospital (BWH) are introducing creative new ways to address medical problems.
In this video, Jeffrey Karp, PhD, Director of the Laboratory for Accelerated Medical Innovation, discusses how his research team, including biologists, immunologists, engineers, polymer scientists, chemists, and clinicians, is using bio-inspiration to drive medical innovation. Examples include the team’s study of porcupine quills to develop next-generation surgical staples and spiny-headed worms to construct a new type of adhesive patch for skin grafts....
Why does this talk matter now? What impact do you hope the talk will have?
Solving medical problems is very challenging; we often encounter barriers that seem insurmountable. Instead of relying on our limited intellect and narrow thinking, there is opportunity for us to turn to nature for inspiration. Every living thing has overcome an enormous number of challenges; in essence, we are surrounded by solutions. My hope is that this talk will help others, through inspiration from nature, overcome challenges they face.
What is the legacy you want to leave?
Innovation is not simply coming up with new ideas. I believe that being innovative means actually doing things that help people. Thus, innovation can only be retrospectively defined. My hope is that when I look back on my career, I can claim that many of the projects that we pursued were innovative....
Taking inspiration from nature seems very popular right now. Why is that? :
Bio-inspiration is an idea that has been around a long time, but it’s only recently that we’ve seen tangible examples applied to everyday problems and actively shared by social media. Based on the super-hydrophobic properties of lotus leaves, surfaces have been developed that can repel water – and they may one day make windshield wipers more effective or even unnecessary; tree frog toes have inspired tyre treads; and several research groups have mimicked gecko adhesion to create tapes that allows robots to climb walls. It’s supercool.
What is the difference between bio-inspiration and biomimicry? Is it more than terminology?:
As the name suggests, biomimicry is where you copy directly from nature. Bio-inspiration, on the other hand, is where you take an idea from nature and find a way to improve on it for your own purposes....
Jeffrey Karp, Associate Professor at Harvard Medical School and Co-Director of the Center for Regenerative Therapeutics at the Brigham and Women’s Hospital, will share unexpected insights into the field of bio-inspiration, the art and science of adapting medical tools, treatments, and technologies from solutions found in nature.
Canadian Jeff Karp’s research focuses on stem cell engineering, biomaterials, and medical devices inspired by nature. He has many inventions to his name including slug-inspired tissue glues, parasitic worm-inspired microneedles, jellyfish-inspired cell-sorting chips, and a gecko-inspired medical tape. Jeff’s other innovations include a novel neonatal skin adhesive and a nanoparticle prophylactic approach to prevent contact dermatitis. Jeff is an acclaimed mentor and is most proud of the 13 trainees he has launched into faculty careers around the globe. He is an Associate Professor of Harvard Medical School at the Brigham and Women’s Hospital, a principal faculty member at the Harvard Stem Cell Institute, and Affiliate Faculty at MIT through the Health Sciences & Technology program....
Following a tissue graft transplant — such as that of the face, hand, arm, or leg — it is standard for doctors to give transplant recipients immunosuppressant drugs immediately to prevent their immune systems from rejecting and attacking the new body part. However, that incurs the risk of toxicities and side effects, because suppressing the immune system can make a patient vulnerable to infection.
In a global collaboration, researchers from Harvard-affiliated Brigham and Women’s Hospital (BWH), the Institute for Stem Cell Biology and Regenerative Medicine in Bangalore, India, and University Hospital of Bern, Switzerland, have developed a way to deliver immunosuppressant drugs locally and when prompted, through the use of a biomaterial that self-assembles into a hydrogel, a gelatinlike material. The novel system is able to targeted and controlled release of the medication, so that it is delivered where and when it is needed.
The study was published online today in Science Translational Medicine.
The hydrogel-drug combo, which contains the immunosuppressant drug tacrolimus, is injected under the skin after transplant surgery. The hydrogel remains inactive until it detects an inflammation/immune response from the transplant site, at which point it delivers the immunosuppressant drug within the transplanted graft for months.
In pre-clinical studies conducted by the researchers, a one-time, local injection of the hydrogel-drug combo prevented graft rejection for more than 100 days. This compared with 35.5 days for recipients receiving only tacrolimus, and 11 days for recipients without treatment or only receiving hydrogel.
The innovation may also be applied in medical situations outside of transplant surgery.
“This new approach to delivering immunosuppressant therapy suggests that local delivery of the drug to the grafted tissue has benefits in reducing toxicity, as well as markedly improving therapeutic outcomes, and may lead to a paradigm shift in clinical immunosuppressive therapy in transplant surgery,” said Harvard Medical School associate professor of medicine Jeff Karp, Division of Biomedical Engineering, BWH Department of Medicine, co-corresponding study author....
Harvard stem cells scientists at Brigham and Women’s Hospital and MIT can now engineer cells that are more easily controlled following transplantation, potentially making cell therapies, hundreds of which are currently in clinical trials across the United States, more functional and efficient.
Associate Professor Jeffrey Karp, PhD, and James Ankrum, PhD, demonstrate in this month’s issue of Nature Protocols how to load cells with microparticles that provide the cells cues for how they should behave over the course of days or weeks as the particles degrade.
“Regardless of where the cell is in the body, it’s going to be receiving its cues from the inside,” said Karp, a Harvard Stem Cell Institute Principal Faculty member at Brigham and Women’s Hospital. “This is a completely different strategy than the current method of placing cells onto drug-doped microcarriers or scaffolds, which is limiting because the cells need to remain in close proximity to those materials in order to function. Also these types of materials are too large to be infused into the bloodstream.”...
Researchers at MIT and Brigham and Women’s Hospital have shown that they can grow unlimited quantities of intestinal stem cells, then stimulate them to develop into nearly pure populations of different types of mature intestinal cells. Using these cells, scientists could develop and test new drugs to treat diseases such as ulcerative colitis.
The small intestine, like most other body tissues, has a small store of immature adult stem cells that can differentiate into more mature, specialized cell types. Until now, there has been no good way to grow large numbers of these stem cells, because they only remain immature while in contact with a type of supportive cells called Paneth cells.
In a new study appearing in the Dec. 1 online edition of Nature Methods, the researchers found a way to replace Paneth cells with two small molecules that maintain stem cells and promote their proliferation. Stem cells grown in a lab dish containing these molecules can stay immature indefinitely; by adding other molecules, including inhibitors and activators, the researchers can control what types of cells they eventually become....
Jeffrey Karp, PhD, of the Division of Biomedical Engineering in BWH’s Department of Medicine, and Bohdan Pomahac, MD, director of Plastic Surgery Transplantation, have been honored with the Innovative Product of the Year Award from the Institution of Chemical Engineers (IChemE) for their research on worm-inspired microneedle tissue adhesives. These adhesives have the potential to replace sutures and staples for some surgical applications and can be used to deliver agents, including large molecule peptides and proteins, to prevent infection or accelerate regeneration. They are also working together to explore applications in skin grafting....
Jeffrey Karp, PhD, associate professor in BWH’s Department of Medicine, has been honored as the runner up in the Cell Press Reader App Competition. Karp conceived of an app that would list the top ten papers with the most citations that week, in the Cell Press Journal Reader App.
His idea is to list the top ten papers with the most citations that week together with the number of citations, this could also be presented as the top ten cited papers of the year and updated weekly. The feature would help keep the community informed of leading edge papers and how research is changing over time. Cell Press is advancing this concept towards implementation....
Scientists have inserted mRNA into mesenchymal stem cells (MSCs) to produce a drug delivery vehicle. Following systemic administration, the modified MSCs targeted and adhered to sites of inflammation, then released interleukin-10 that significantly reduced local swelling.
Historically, MSC-based treatments have had mixed results. MSCs exert their therapeutic effects in hit-and-run style. That is, MSCs are rapidly cleared after entering the bloodstream, typically within a few hours or days. Yet, despite the transience of MSC therapeutic action, a team of scientists reports that it has engineered MSCs that rapidly localized at a distant site of inflammation in an in vivo model, and delivered therapeutically relevant concentrations of the drug. The MSCs had been engineered enhanced homing and the expression of interleukin-10, which is not inherently produced by MSCs.
The team of scientists included members representing Brigham and Women’s Hospital, the Harvard Stem Cell Institute, MIT, and Massachusetts General Hospital. The team, which published the results of its proof-of concept study in the October 3 issue of Blood, notes that its work is already drawing interest from biopharmaceutical companies....
An adhesive inspired by a parasitic worm could help better affix skin grafts in burn patients.
Bioengineer Jeffrey Karp is used to finding inspiration in unusual places. He’s looked to porcupines’ barbed quills and the sticky pads of geckos’ feet, for example, to develop medical adhesives. And one afternoon a few years ago he sat in his office with some of his lab members Googling parasites.
Karp, an associate professor at Harvard Medical School and Brigham and Women’s Hospital, was hoping to create a new medical adhesive for wet soft tissues, such as the gut’s lining or the exposed flesh of burn victims. “There’s been very minimal innovation in the clinic in terms of adhesives in the past several decades,” he says.
He and his team reasoned that they could model this new adhesive on the tricks of a parasite that glommed onto its host’s insides.
The group stumbled upon a paper that mentioned the spiny-headed worm (Pomphorhynchus laevis), which lives inside the guts of fish (PLOS ONE, 6:e28285, 2011). An electron micrograph in the paper showed the worm’s unusual method of attaching itself: the tip of its proboscis swells once inside its host’s flesh, anchoring the worm to the gut.
Karp’s team developed an adhesive device that consists of a sheet of microneedles whose tips swell upon contact with water, which could be used to adhere skin grafts to wounds, deliver drugs to target tissues, and for many other potential applications (Nat Comm, 4:1702, 2013)....
Say you’re looking to make the next generation of medical tape. You want something that will hold skin and other organs together while they heal. You want it to be more convenient than sutures and less brutal than staples. It has to stick easily, hold on tightly, and come off painlessly.
There are worse places to search for inspiration than the guts of a fish.
Fish intestines are home to a group of parasites called spiny-headed worms, or acanthocephalans. Their most distinctive feature is a spine-covered snout that the worm stabs into the gut walls of its host. Once inside, it contracts two muscles and the long snout rapidly swells into a bulb, anchoring the worm in place. The fastened parasite can now drink deeply from the river of nutrients washing over it, absorbing them through its skin.
To the fish, the worm’s spiny head is a health hazard. To Jeffrey Karp, it was something to emulate. His team at the Brigham and Women’s Hospital in Boston have spent many years developing medical adhesives, constantly looking to nature for inspiration. In 2008, for example, they developed a sticky tape based on the feet of a gecko. And last year, they created artificial microneedles based on a porcupine’s quills, whose structure allows them to easy to stab into flesh but hard to pull back out.
Geckos are famously sticky, and porcupines are famously stabby, but Karp also realised that parasites must have fantastic ways of fastening themselves to their hosts. That’s how he came across the spiny-headed worms and one species in particular—Pomphoryhnchus laevis....
The North American porcupine is easily recognizable due to its impressive coat of long, sharp quills. These unique projections are designed so that they can easily penetrate animal flesh, but are extremely difficult to remove. While this may be bad news for a predator or a curious pet, this natural mechanism is a boon for a curious medical researcher trying to develop a better medical device.
A research team led by Jeffrey Karp, PhD, Brigham and Women’s Hospital (BWH) Division of Biomedical Engineering, Department of Medicine, collaborating with Massachusetts Institute of Technology’s (MIT) Robert Langer, PhD, have figured out the secret to the porcupine quill’s easy-in, not-so-easy-out design and demonstrated how that design could be applied to developing a better medical needle or adhesive patch.
The researchers worked with natural porcupine quills and molded polyurethane quills (mimicking the structure of natural quills) to help them understand the forces involved. They discovered that a quill’s geometry, particularly its sleek backward facing barbs, is instrumental in its ability to easily penetrate tissue and subsequently prevent easy extraction....
One late evening in a coffee shop near McGill University, Jeff Karp overheard two students talking about drug delivery and tissue engineering. Jeff, an undergrad, listened closely as the students discussed two graduate level courses. At the time Jeff was questioning his major. He had switched from biology to chemical engineering but found himself bored in class; uninterested in the details of how refrigerators work. That night at the coffee shop Jeff learned about two classes that he became desperate to take: one on artificial organs and engineering and the other on cells and biotechnology. To enroll he would need to take no less than 5 prerequisite physiology classes. Undeterred, Jeff added a year to his undergrad studies and switched majors yet again, this time to biomedical engineering. He had finally found the right balance between medicine and engineering. Jeff says a “degree in engineering is a degree in problem-solving” and that he uses the skills he learned in undergrad every day....
e medical tape that physicians use today is quite good at keeping medical devices attached to the skin. Unfortunately, that same sticky tape also can be quite hard to get off – particularly when used on newborns or elderly patients – which often results in severely damaged skin.
But thanks to a little green lizard, an eight-legged arachnid, and researchers at Brigham and Women’s Hospital (BWH), patients may soon benefit from a new type of medical tape that holds strong when you need it to, but also peels off easily.
The Institute for Pediatric Innovation established the need for such an adhesive after surveying neonatal clinicians nationwide. Then they asked Jeffrey Karp, PhD, BWH Division of Biomedical Engineering, Department of Medicine, and Robert Langer, PhD, Massachusetts Institute of Technology, to develop it.
As they often do, Dr. Karp’s team found inspiration in nature....
Scientists build a device with long strands of DNA tied to a microchip that floats in bloodstream.
Tiny strands of DNA that float like jellyfish tentacles can grab and hold tumor cells in the bloodstream in a device inspired by nature that may help cancer patients fight the dreaded disease.
The device can be used to both count and sort cancer cells, which is an important indicator of how well chemotherapy or other treatments are working. Doctors need to know whether cancer cells are being knocked out or developing immunity.
“The key is to know which drugs the remaining cells would be most susceptible to,” said Jeffrey Karp, an author on the paper published today in the Proceedings of the Natural Academy of Science (PNAS) and co-director of the Center for Regenerative Therapeutics at Brigham and Women’s Hospital in Boston. “Often these cells in the blood stream are at very low concentrations and it’s difficult to isolate them. What you really want to do is collect them and study the biology of the cells and subject them to different kinds of chemo so you know which one is best to use.”...
In August of this year, Allison Noles rushed her bulldog Bella Mae to the vet. The dog’s face looked like a pincushion, with some 500 spines protruding from her face, paws and body. The internet is littered with such pictures, of Bella Mae and other unfortunate dogs. To find them, just search for “porcupine quills”.
North American porcupines have around 30,000 quills on their backs. While it’s a myth that the quills can be shot out, they can certainly be rammed into the face of a would-be predator. Each one is tipped with microscopic backwards-facing barbs, which supposedly make it harder to pull the quills out once they’re stuck in. That explains why punctured pooches need trips to the vet to denude their faces.
But that’s not all the barbs do. Woo Kyung Cho from Harvard Medical School and Massachusetts Institute of Technology has found that the barbs also make it easier for the quills to impale flesh in the first place. “This is the only system with this dual functionality, where a single feature—the barbs—both reduces penetration force and increases pull-out force,” says Jeffrey Karp, who led the study....
Understanding the mechanisms behind quill penetration and extraction could help engineers design better medical devices.
Anyone unfortunate enough to encounter a porcupine’s quills knows that once they go in, they are extremely difficult to remove. Researchers at MIT and Brigham and Women’s Hospital now hope to exploit the porcupine quill’s unique properties to develop new types of adhesives, needles and other medical devices.
In a new study, the researchers characterized, for the first time, the forces needed for quills to enter and exit the skin. They also created artificial devices with the same mechanical features as the quills, raising the possibility of designing less-painful needles, or adhesives that can bind internal tissues more securely.
There is a great need for such adhesives, especially for patients who have undergone gastric-bypass surgery or other types of gastric or intestinal surgery, according to the researchers. These surgical incisions are now sealed with sutures or staples, which can leak and cause complications....
A research team at Harvard-affiliated Brigham and Women’s Hospital (BWH) has developed a novel device that may one day have broad therapeutic and diagnostic uses in the detection and capture of rare cell types, such as cancer cells, fetal cells, viruses, and bacteria. The device is inspired by the long, elegant appendages of sea creatures such as jellyfish and sea cucumbers.
The study will be published online on Nov. 12 in Proceedings of the National Academy of Sciences.
The device, a microchip, is inspired by a jellyfish’s long, sticky tentacles that are used to capture minuscule food flowing in the water. The researchers designed a chip that uses a 3-D DNA network made up of long DNA strands with repetitive sequences that — like the jellyfish tentacles — can detect, bind, and capture certain molecules.
The researchers, led by senior study author Harvard Medical School Associate Professor of Medicine Jeffrey Karp, of the Division of Biomedical Engineering in the Department of Medicine at BWH, and co-author Rohit Karnik, of the Massachusetts Institute of Technology, created the chip using a microfluidic surface and methods that lets them not only to rapidly replicate long DNA strands with multiple targeting sites that can bind to cancer cells but also to customize critical characteristics, such as DNA length and sequence, which allowed them to target various cell types....
Ripping off a Band-Aid may sting for a few seconds, but the pain is usually quickly forgotten. However, for newborns’ sensitive skin, tearing off any kind of adhesive can pose a serious risk.
Newborns lack an epidermis — the tough outermost layer of skin — so medical tape used to secure respirators or monitoring devices critical for the survival of premature babies can wreak havoc: Every year, more than 1.5 million people suffer scarring and skin irritation from medical tape, and the majority of those are infants or elderly people, who also have fragile skin.
“This is just a huge unmet need,” says Jeffrey Karp, an associate professor of medicine at Harvard Medical School and co-director of the Center for Regenerative Therapeutics at Brigham and Women’s Hospital....
Taking medical tape off an adult isn’t too painful because breakage occurs in the glue (you can sometimes see the leftover residue). But removing the same adhesive from a newborn can break fragile skin, causing significant damage, says Jeffrey Karp, researcher at Brigham and Women’s Hospital in Boston.
Traditional medical tape has two layers: the sticky one and the non-sticky one that forms the backing. The adhesive is designed for adults, Karp said; newborns need something else just for them.
In the neonatal intensive care unit tape often needs to be changed, Karp said. If the tape is on a joint, peeling the fragile skin can cause mobility problems.
“The kids are just completely helpless here,” he said.
Karp, Robert Langer of the Massachusetts Institute of Technology, and Bryan Laulicht of Brigham and Women’s wanted to solve this problem by designing a tape that doesn’t damage sensitive skin when it’s removed. They’ve published a study in the Proceedings of the National Academy of Sciences describing their idea for a solution, which hasn’t yet been tested clinically....
Researchers at Brigham and Women’s Hospital and other hospitals have taken a step toward making stem cell therapies more effective by adding homing receptors to those cells.
Attaching the chemical receptors to stem cells has the potential to increase the concentration of cells at target locations in the body, according to the researchers, who published their findings in the journal Blood. The development was reported by Brigham and Women’s in a press release.
“The central hypothesis of our work is that the ability of cells to home to specific tissues can be enhanced, without otherwise altering cell function,” said corresponding author Jeffrey M. Karp, PhD, co-director of the Regenerative Therapeutics Center at BWH and a principal faculty member of the Harvard Stem Cell Institute in the press release. “By knowing the ‘zip code’ of the blood vessels in specific tissues, we can program the ‘address’ onto the surface of the cells to potentially target them with high efficiencies.”...
Stem cell therapies hold enormous potential to address some of the most tragic illnesses, diseases, and tissue defects world-wide. However, the inability to target cells to tissues of interest poses a significant barrier to effective cell therapy. To address this hurdle, researchers at Brigham and Women’s Hospital (BWH) have developed a platform approach to chemically incorporate homing receptors onto the surface of cells. This simple approach has the potential to improve the efficacy of many types of cell therapies by increasing the concentrations of cells at target locations in the body. These findings are published online in the journal Blood on October 27, 2011.
For this new platform, researchers engineered the surface of cells to include receptors that act as a homing device. “The central hypothesis of our work is that the ability of cells to home to specific tissues can be enhanced, without otherwise altering cell function,” said corresponding author Jeffrey M. Karp, PhD, co-director of the Regenerative Therapeutics Center at BWH and a principal faculty member of the Harvard Stem Cell Institute. “By knowing the ‘zip code’ of the blood vessels in specific tissues, we can program the ‘address’ onto the surface of the cells to potentially target them with high efficiencies.”...
Although Jeffrey Karp knew from childhood that he wanted to be a medical man, it was almost pure chance that led him to the field of bioengineering.
“While studying for an exam in a coffee shop, I overheard some colleagues discussing tissue engineered organs, drug delivery and ‘artificial blood substitutes,” said Karp, now co-director of regenerative therapeutics at Brigham and Women’s Hospital. “I asked them what they were studying, and they told me about two graduate physiology courses called artificial blood and immobilization biotechnology, and artificial internal organs. I decided then and there to take these courses — which required me to extend my undergrad by a year and take a bunch of physiology prerequisite courses,”
Karp said the “decision drew me into the field of bioengineering and I haven’t looked back.”...
Two researchers from the Center for Biomedical Engineering and the Regenerative Therapeutics Research Center at Brigham and Women’s Hospital (BWH) have been awarded the 2011 Young Investigator Award from the Society for Biomaterials (SFB). Jeffrey Karp, PhD, and Ali Khademhosseini, PhD, MASc, will receive their awards at the SFB Annual Meeting and Exposition in Orlando, Florida in April 2011....