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Jeffrey Karp is a world leader in the emerging field of biomimicry, which turns to nature for answers to complex human problems. Karp is an Associate Professor at Brigham and Women’s Hospital, Harvard Medical School, Principal Faculty at the Harvard Stem Cell Institute, and an affiliate faculty at the Broad Institute. Photo: Jeffrey Karp

Research is hard. There are so many variables in scientific exploration, no wonder it is exponentially challenging. 

But what if there was a blueprint? What if there was a previous version proven effective, with slight modifications needed? 

Those in the field of biomimicry would argue there is—it’s called nature. 

“Nature is the best problem-solver,” Jeffrey Karp, a bioengineer at MIT, told Laboratory Equipment. “It’s hundreds of millions of years of research and development happening all around us.”

Karp would know. He’s one of the country’s foremost experts in biomimicry—the imitation of models, systems and elements of nature for the purpose of solving complex human problems. Karp has published more than 100 peer-reviewed papers (with 11,400+ citations) and has 70 issued or pending patents. His research has led to several marketable products and associated company spin-offs, as well as additional products currently in clinical trials. 

“By looking at nature for new ideas, you are going to find ideas you would never have thought of if you stayed in the lab and used mainstream thinking,” Karp said. 

If you are envisioning a bunch of scientists standing outside staring at trees, you’re not far off base; but there’s so much more to the trend that Fortune listed as No. 1 for 2017. 

“It’s about the process of not just deeply observing that tree I’m looking at right now, but the whole system around it,” explained Beth Rattner, executive director of the Biomimicry Institute. “That tree is sharing nutrients with how many other living things around it; it’s about looking at the structures of the tree to see how it’s doing that. Or if a limb gets knocked off in a storm. The plumbing system of a tree is completely radiant, it goes around the external parts of the tree. It’s prepared to sacrifice a limb if it has to. Why then do we design buildings to be so linear and non-resilient when we know things break and fractures happen? If we would start designing our buildings like trees, for example, it would mean something fundamentally different.”

The Biomimicry Institute was founded in 2006 by the mother of the field Janine Benyus, who literally wrote the book on the discipline—“Biomimicry: Innovation Inspired by Nature” was published in 1997. The non-profit institute is dedicated to making biology a natural part of the design process through education, starting at the K-12 level. The Institute’s emphasis is on sustainable designs through nature for a healthy planet. 

“It’s not just about creating mechanical bees, but can we actually get there with something that is truly sustainable that is going to make sure people have jobs, that forests stay intact, that the air stays clean, the water stays healthy,” Rattner told Laboratory Equipment. “Those things are possible if we just design better.”

The gecko-inspired adhesive patch that started it all for Jeffrey Karp almost 10 years ago. Photo: Jeffrey Karp

Geckos and hearts

Karp’s research and innovations have been inspired by a plethora of animals—porcupines, spiders and parasites to name a few—but none perhaps as well-known, and transformative, as the gecko-inspired bandage. 

Created almost 10 years ago by drawing on the principles that make gecko feet unique, the surface of the bandage has the same kind of nanoscale hills and valleys that allow the lizards to cling to walls and ceilings. Layered over this landscape is a thin coating of glue that helps the bandage stick in wet environments, such as heart, bladder or lung tissue. And because the bandage is biodegradable, it dissolves over time and does not have to be removed.

By the time Karp began his research, Gecko-like adhesives had been around for years, with one fatal flaw—they could not be adapted for medical applications given stringent design criteria and federal regulations. Karp and his colleagues, including MIT professor Robert Langer, solved this problem by designing their material with a custom “biorubber” also invented in the lab. 

Not even two years after the gecko tape debuted, Karp was contacted by Dr. Pedro del Nido, the chief of cardiac surgery at Boston Children’s Hospital. del Nido had read Karp’s paper and thought perhaps he could help with a major problem—sealing surgical wounds on the hearts of babies. 

Because del Nido’s patients are so young, he found that their heart tissue often tore while he was trying to suture. There are medical devices that provide this kind of wound-sealing in adults, but they can’t be used for children due to their size and the fact that they are permanent. A child fitted with the adult device would need to have multiple revision procedures as the heart and body grow. 

Although Karp’s gecko tape could seal tissue, it wouldn’t work in this instance since the heart is not stationary. Current surgical glue wasn’t an option either as they needed something that could withstand movement and survive in the harshest, most dynamic environment in the human body.

Once boiled down, the question for Karp became, “how can we create a material that is flexible enough to beat with the human heart, but is strong enough that it won’t be washed away by blood?”

Nature had already answered that question in the form of slugs, snails and sandcastle worms.

“These creatures have a number of things in common, including viscous secretions, which serves a purpose—adhesive interactions. These viscous secretions also contain hydrophobic agents, which can repel water. We were intrigued by that and tailored our glue with these concepts in mind. It took us in a direction no one had gone before,” explained Karp. 

Thus, Karp and his lab began to develop a tissue patch inspired by slug secretions. The end result was a patch that is fully degradable, elastic and transparent (so the glue can be cured with light). The elasticity allows the patch to move with the beating heart; while the patient’s own cells can migrate on top of it, forming new tissue as the foreign patch degrades over time. Karp also developed an easy-to-use device that emits a visible LED ray of light to cure the glue in seconds once it is set. 

After the glue performed well in animal studies with pigs, Karp launched a spinoff company called Gecko Biomedical, headquartered in Paris. With Karp’s involvement, the company industrialized the material developed in the lab, and it’s now being tested in a human clinical trial in Europe for vascular reconstruction. 

Inspired by the viscous secretions of slugs and snails, Karp created a glue to seal holes in the hearts of newborns. Here, the glue is being applied to anastomosis. Photo: Jeffrey Karp

More than research

One of the reasons Karp is so recognizable in the field is his ability to push developments past the lab into commercialization, and eventual marketability. 

For instance, Gecko Biomedical is only one of a handful of spinoff companies Karp has founded to accelerate his lab developments. 

One that is set to begin clinical testing in about 18 months is Frequency Therapeutics, which develops small molecule drugs that activate progenitor cells within the body to restore healthy tissue, specifically in the inner ear. 

Karp said he was inspired by a number of creatures in nature who have regenerative capacity, like sharks who regenerate their teeth throughout life or salamanders who can regenerate entire limbs. Karp set out to develop small molecules that could target regeneration in the body without having to remove stem cells, as stem cell therapeutics is a tedious, complex process. 

After years of working to understand the stem cell that regulates regeneration in the human body—like the epithelium layer of the liver that regenerates every five days—Karp and his lab successfully developed a small molecule combination that could target and control these stem cells, called Lgr5+. Realizing that Lgr5+ was also present in the inner ear, Karp and his team, including Langer, were able to expand the number of progenitors that form hair cells by 2,000-fold; thus restoring degenerative hearing loss. 

Frequency Therapeutics is now translating this work into new treatments in the hopes that controlled tissue regeneration has profound therapeutic potential.

Skintifique, another of Karp’s companies, already has products on sale in Europe, Boston and on Amazon. 

Karp and colleagues developed a calcium carbonate-based skin cream for people who have a nickel allergy. The novelty of the cream is that it uses nanoparticles of calcium carbonate. Particles with a diameter of under 20 nanometers can penetrate the skin, but the calcium carbonate particles in this cream are between 70 to 500 nanometers, smaller than a human hair. In this range, they bind to nickel ions and create a barrier to prevent the allergen from contacting skin and subsequently causing a reaction. 

The newest company from Karp and Langer is Alivio Therapeutics, a company dedicated to drug delivery for inflamed tissue. The company’s novel device is based on an innovative hydrogel material Karp developed that is designed to adhere to and deliver drugs to inflamed tissue based on the degree of inflammation—for example, more drugs are released at a site with greater inflammation. 

Chronic and acute inflammation is currently managed by systemic steroids and immunosuppression, which can have serious side effects. Alivio’s proprietary device not only minimizes the risks associated with drug exposure to healthy tissues, but may also enable new, disease-modifying drugs that can be delivered with maximum efficiency. 

Multi-disciplinary wave

Karp describes himself as a medical “problem-solver,” rather than the more traditional medical device engineer or researcher. This moniker gives him the freedom to look across the spectrum of medical issues for applications where biomimicry could apply, as opposed to focusing on a specific disease or technology. 

“We’re focused on problems,” Karp said. “That’s the structure of the lab, and that’s what connects everything. We’re trying to solve medical problems, and using all the possible resources we have at our disposal.”

Unsurprisingly, Karp’s lab is distinguished by its lateral working environment and highly multi-disciplinary approach—a key component of biomimicry. 

Materials scientists, biologists, clinicians, surgeons and doctors have all been a part of Karp Lab, not to mention researchers from more than 30 countries simultaneously working on 20 to 25 different projects. 

“The work I do is highly collaborative,” Karp said. “We don’t work in a siloed environment. We have a lot of collaborators, and augment each others’ expertise. It’s really important for us to maximize our impact and our productivity, and learn to work with others from completely different disciplines. It’s about having a multi-disciplinary environment and creating a training ground in my lab to train the next generation of innovators in medicine.”

Indeed, Karp is viewed as a valuable mentor both inside and outside the MIT campus. In 2008, he was selected as the Outstanding Faculty Undergraduate Mentor at MIT; and in 2010, the Harvard-MIT Health, Sciences and Technology division granted him the McMahon Mentoring Award as the year’s top mentor.

Although biomimicry has been around for decades, some experts say its future—including its future researchers—is more important than ever given the world’s population growth, resource constraint, climate change and other ominous problems.  

“We need to get biomimicry to scale, and we need it to scale quickly, because as a species I don’t think we have a lot of time,” Biomimicry Institute’s Rattner said. “The advantage to biomimicry is you are literally looking at models of adaptation that have worked. If we are time-constrained, this is a system we know works.

“We’re starting to see progress on so many fronts that I really do think we’re right at the beginning of what’s going to be a massive wave. We’re looking at a wave of biologically inspired innovation, and my hope is we can get there quickly and with fidelity,” she concluded.

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