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From the campus of Harvard Medical School, this is ThinkResearch, a podcast devoted to the stories behind clinical research. I'm Oby, your host. ThinkResearch is brought to you by Harvard Catalyst, Harvard University's Clinical and Translational Science Center, and by NCATS, the National Center for Advancing Translational Sciences.

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Oby Ukadike: On the last episode of ThinkResearch, we re-aired an interview we did with Dr. Benjamin Freedman about his research in bioadhesives using slugs as inspiration. Today, we hear from him again as he catches us up on the progress of his research and some new discoveries he and his team have made. We hope you enjoy this episode.

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Benjamin Freedman: It's great to be back on this podcast to share some of our latest since the initial podcast back in 2022. A lot's changed since then. A lot of new exciting developments have been made with our technology, the team, it's translational potential. So excited to share some of those here today.

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So my experiences as a parent, scientist, and entrepreneur deeply influenced the work that I do. Since the last podcast, we now have two sons. It's really reinforced my curiosity, resilience, and long-term thinking, qualities that I think translate directly into both scientific discovery and leadership.

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In addition to my dual roles, both leading a lab, as well as supporting a startup, really balancing both has given me an even greater appreciation for building, mentoring, and enabling talented teams to push forward new ideas. What continues to drive me every day is the excitement of new and disruptive science. The kind of breakthroughs that challenge conventional thinking and redefine what's possible in medicine are things that really excite me.

I'm especially motivated by the conversations about what the future looks like, imagining emerging technologies that might cure disease, that might transform patient care, and hopefully, fundamentally change the lives of patients.

Beyond the science, I think there's immense value in talking directly with end users to gain real-feedback. These end users can involve a number of different folks, whether it be customers or clinicians or patients.

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We're really seeing firsthand how a technology is used, where it falls short. What truly matters in a clinical setting allows our teams to bridge the gap between innovation and practical impact. These conversations validate the need for new solutions. They also inspire continuous iteration and improvement. This helps to ensure that our work translates into meaningful, real-world change.

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So since we last spoke, there's been a number of exciting developments in our research. I'll highlight some of the most recent advances in the science.

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As we talked about a couple of years ago, we're developing a bioadhesive material inspired by the adhesive slime that snails and slugs secrete when they feel threatened. Back in the early part of 2022, we had been developing this technology while I was a postdoc in Dave Mooney's group at the Wyss Institute at Harvard.

I think a couple of months after we did the podcast, we ended up winning the 2022 Harvard's President's Innovation Challenge, which was which was quite exciting. And now we're actually back competing as semifinalists in the alumni category. But since this time, we have published a couple of papers which we think are really impactful and exciting surrounding the technology.

In the earlier part of 2024, we published a paper in PNAS, Proceedings of National Academy of Sciences, basically describing an advance to our existing glue, the new bonding method that enables instant and effective adhesion of hydrogels, which we hope will broadly advance new biomaterial solutions for multiple unmet clinical needs.

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For those tuning in not familiar with hydrogels, they're basically versatile biomaterials that are conquering a number of biomedical areas. They basically consist of water-swollen molecular networks. They can be tailored to mimic the mechanical and chemical features of various organs and tissues. And they can interface within the body and outside the body without causing damage to even some of the most delicate parts of our anatomy.

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So there's hydrogels that are already used in clinical practice. They're used for therapeutic delivery of drugs to fight pathogens. They are used as bone cements. They're used as wound dressings, other blood-coagulating bandages, or even 3D scaffolds that you might hear about for some of the latest in tissue engineering.

But one of the struggles with these materials is their ability to attach quickly and strongly to one another. And this could be important for a number of different areas for complex procedures.

And if we think about achieving rapid adhesion of polymers, this might enable numerous new applications where we could further fine-tune stiffness of materials to better conform to specific tissues. They might enable on-demand encapsulation of flexible electronics for medical diagnostics, or even the creation of self-adhesive tissue wraps for hard to bandage parts of the body.

We kind of discovered, in many ways by mistake, was that we could do this by essentially creating a variant of our adhesive layer. I spoke a little bit about that. The materials are inspired by the adhesive slime that snails and slugs create when they feel threatened. And we've tried to mimic and recapitulate some of these features in our hydrogels. We don't use any snail or slug components. We just use bioinspiration to create materials that behave in a similar way.

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So what we've done here is we basically have modified one of those components, essentially the chitosan base layer, to basically form a very thin film. And what we discovered by mistake was that using this thin film enables us to attach different hydrogels to one another instantly.

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Historically, and in our practice, this typically took on the order of minutes to attach. Sometimes would take very complicated steps involving UV cross-linking to attach a hydrogel to an elastomer or a piece of plastic. But with this new strategy, we can actually do this for certain types of materials instantly.

So we think that this provides a really interesting advance in the science for the overall technology platform. And we demonstrated this in the paper for a few areas, including local cooling of tissues and burns, sealing of vascular injuries, and prevention of unwanted surgical adhesions. So we were really excited about this work, and it ended up getting published, again, in PNAS about exactly one year ago.

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And then more recently, we've done some work in collaboration with some really incredible neurosurgeons in Brigham and the Children's Hospital that initially heard about our work through a press release that the Wyss Institute had issued. That's one of the great things about these types of outreach events, is that oftentimes we get all sorts of interesting inbound inquiries from people tuning in, and this is one of them.

And the only reason this project really kicked off is we had a neurosurgeon who saw a video online and reached out and said, hey, this would be really cool. Have you thought about applying it in neurosurgery? This work was really in close collaboration with Dr. Kyle Wu, who was a resident and fellow at the time, who's now an assistant professor at Ohio State University, who we still collaborate with closely.

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This work was basically aimed at repairing the dura in patients more durably. We basically found that by creating a highly adhesive and mechanically strong, what we call dural-tough adhesive can address multiple limitations in the repair of the dural membrane lining the brain and spinal cord after trauma and surgeries.

So if you're not in the neurosurgery space, basically, the dura-- the dural membrane, or the dura, is the outermost of three meningeal layers that line the central nervous system. It includes the brain and spinal cord. And together, these meninges function as a shock absorber to protect the CNS against trauma. They circulate nutrients throughout the CNS, and they also remove waste.

The dura is basically a critical biological barrier that contains Cerebrospinal Fluid, or CSF for short, and that surrounds all CNS tissues. And unfortunately, when you have spontaneous injury or trauma or other types of surgical procedures, this can cause the CSF to leak. This can threaten patients' lives. It can lead to impaired neurological functions in recovery.

Until you talk to a patient that's really suffered from a CSF leak, is really where you start to learn how much of a pain point this really is for patients and their families and clinicians. So watertight closure is super important in this process. And that's really what led us to work very closely with neurosurgeons in this area.

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The current strategies for repairing the dura are basically suture repair, and then you spray these existing sealants over them. And the problem is that the existing sealants are pretty brittle, which means that they crumble easily. They don't deform well with underlying tissue or pressures, and they can leak. And they can also cause other problems if they swell or have off-target effects.

So what we've tried to do here is develop a newer solution by applying our same material framework to try to essentially repair the dura more durably. So what we did was we applied our materials in a series of model systems. And a lot of this work actually kicked off back in 2019 or so and then went through the pandemic.

We were doing procedures when we were all on essentially our reduced hours and shift work time frame. But we continued to push through, and we did a variety of studies in pigs, as well as in small animals, to evaluate both the biocompatibility as well as performance.

And what we found was that the materials attached very strongly to the dura. They achieved peak burst pressures, orders of magnitude beyond many commercial products. And then on top of that, they were found to have really excellent biocompatibility to underlying tissues and outperformed the existing competitors in a live animal acute setting when we tried to pressure-test their performance in realistic-type scenarios.

So we're really quite excited about the initial work that we've done in this space. The paper came out in Science Translational Medicine in April of 2024, and we were excited that it was picked up by the director of the NIH, who tweeted about it online, and it caught quite a bit of attention at the time. We're hoping that this could be another indication that it is translated with these materials to hopefully one day improve patient outcomes.

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You know, more broadly speaking, that's a lot of advancement on the technology side. Since we last had the podcast, the technology was really just still within the Institute. And since then, it's taken a number of exciting steps, largely in partnership through the Gates Foundation, where it allowed us to recruit a small team to further continue working on the technology, set up independent space nearby at the Blavatnik Life Lab, utilize resources, and start to make impact in a number of different areas. So that's been a really exciting step for the technology as it's getting closer to making impact on patients.

As we look ahead in terms of the next steps and goals in this research journey, our primary goals are to expand the technology while ensuring long-term sustainability and innovation. So given some of the recent uncertainty in governmental funding, we're actively working to diversify funding sources by exploring industry partnerships, philanthropic opportunities, and venture-backed initiatives to support the continued advancement of this important work.

Beyond funding, we're committed to building and strengthening a diverse multidisciplinary team, bringing together really talented individuals-- scientists, engineers, entrepreneurs-- who can drive discovery from bench to bedside. Our team firmly believes that a collaborative and inclusive environment is essential for fostering innovation and translating ideas into real-world solutions.

We also aim to amplify our research and our work in science by presenting our findings and engaging within the broader scientific community and actively sharing this knowledge, whether it be through conferences, publications, strategic collaborations, or other means to communicate and share what we're doing. We see this as a really critical step in transforming breakthroughs into actionable impact. And I think nowadays, this becomes ever increasingly important in the climate that we are living in.

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Ultimately, our goal is to ensure that our work not only advances science, but also reaches patients and clinicians who need it most. One fun example of this is that we had our technology in a museum in New York City. There's an image where I'm supporting a heart with a hydrogel, and it's hanging in the Cooper Hewitt Smithsonian Museum.

And a surgeon, who was local in the area, had come by, saw the exhibit, got my contact information somehow, and we ended up planning a whole series of experiments together to explore a new indication area, and it's possible that this may take off to be a new, exciting endeavor for the technology.

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As we look ahead, I think there's a few areas that I think really deserves some more attention. So I think one area that deserves continued attention is the importance of training, funding, and supporting research at all levels. And that's really important here, as we're talking about investing in early stage career scientists and innovative research programs, which are really essential for driving future breakthroughs.

I've personally benefited from the system. I was once an undergraduate researcher at the NIH. And that experience played an instrumental role in shaping my career. It provided me with early resources, mentorship-- mentorship which I still have today, as I still keep in touch with all of my former PIs that I was in touch with as an undergraduate.

In addition to all these other goals with translating technology and building labs and enterprises, I really want to ensure that the next generation has similar, if not greater, opportunities to advance science and innovation.

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It's a sustained investment in research that not only fuels discovery, but also strengthens our ability to tackle critical scientific and medical challenges. In part, we're doing this not only with the work that we're doing directly in my lab and our startup, but we also have a new aging accelerator grant that we've received from the National Institute on Aging, aimed at really providing additional resource to trainees as they're going through their training to understand and experience entrepreneurship and innovation at multiple different levels.

A lot of activity in these different areas-- not enough activity, I think, across the board and the climate that we are in, but I think some areas to be optimistic about as we look into the days and months ahead.

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Thanks again very much for inviting us to come back. Hopefully, at the next call, we've had the technology in humans and are on our way towards approvals to really get this technology from bench to bedside.

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Oby Ukadike: Thank you for listening. If you've enjoyed this episode, please rate us on iTunes and help us spread the word about the research taking place across the Harvard community and beyond. We are always looking to connect and collaborate with the research community. So if you are looking to collaborate or be a guest, please feel free to email us at onlineeducation@catalyst.harvard.edu.

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