Cooling away the pain: Pusan National University researchers develop bioresorbable, implantable device to block pain signals from peripheral nerves

Owing to their high efficacy, opioids are used widely for the management of neuropathic pain, despite the increasing rates of opioid addiction and deaths due to overdose. To avoid these side effects, there is an urgent need for pain management approaches that can substitute opioid use.

It is well known that cold temperatures numb the sensation in our nerves. Evidence suggests that cooling peripheral nerves can in fact reduce the velocity and amplitude of neural signals that cause pain, leading to pain relief. What’s great about this approach is that if made possible, it will be completely reversible and non-addictive.

To this end, a team of researchers led by Professor Min-Ho Seo from Pusan National University developed a soft, bioresorbable, implantable device with the potential to cool peripheral nerves in a minimally invasive, focused manner. “Scientists already knew that low temperatures could numb the nerves in the body. But demonstrating this phenomenon with a small device at a clinical level was not an easy task,” said Prof. Seo while discussing the study, which was published in Volume 377 Issue 6601 of Science on June 30, 2022.

To develop the device, the team designed a microfluidics system formed with a bioresorbable material—poly(octanediol citrate)—with interconnects carrying a liquid coolant to a serpentine chamber. To top it off, a Magnesium temperature sensor for real-time temperature monitoring was incorporated at its distal end. The intensity and localization of the cooling effect was regulated by perfluoro pentane (PFP) and dry nitrogen gas (N₂)—the two components of the liquid coolant, as well as the geometry of the serpentine chamber.

Next, the team tested the device by implanting it into the sciatic nerves of living rat models with neuropathic pain associated with spared nerve injury. After a three-week evaluation, the team found that the device successfully delivered cooling power to the peripheral nerves of the rats, which led to a reduction in their pain. Fortunately, the delivery of the cooling power occurred in a minimally invasive, stable, and precise manner. What’s more, this application was localized and reversible, and remained effective for almost 15 minutes during one session.

On being submerged in phosphate-buffered saline solution at 75°C, the device, which was made of bioresorbable materials, dissolved within 20 days and got eliminated in approximately 50 days. These findings imply that it has the potential to naturally degrade and get resorbed in the human body.

So, what are the future applications of this device? “The developed device can be used to treat pain after surgery. Since it is connected to an external source of fluid and power like a commercial intravenous (IV) device, it can easily be controlled by the patient. This way, our implantable device will be able to provide targeted and individualized relief without the drawbacks of the addictive pain medications,” said Prof. Seo in response.

With such progress underway, patients with neuropathic pain will finally be able to receive safe and sustainable treatment, without the risk of adverse effects associated with opioid use!

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Reference

DOI: https://doi.org/10.1126/science.abl8532

Authors: Jonathan T. Reeder^1,2,3, Zhaoqian Xie^4,5, Quansan Yang^3,6†, Min-Ho Seo^2,3,7†, Ying Yan⁸, Yujun Deng⁹, Katherine R. Jinkins³, Siddharth R. Krishnan^2,3, Claire Liu^3,10, Shannon McKay¹⁰, Emily Patnaude¹⁰, Alexandra Johnson¹⁰, Zichen Zhao^4,5, Moon Joo Kim¹¹§, Yameng Xu¹², Ivy Huang^2,3, Raudel Avila⁶, Christopher Felicelli¹³, Emily Ray¹⁴, Xu Guo^4,5, Wilson Z. Ray^8,14, Yonggang Huang^2,3,6,15, Matthew R. MacEwan^8,14, John A. Rogers^{2,3,6,10,16,17,18}

Affiliations:

¹Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR, USA

²Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA

³Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA

⁴State Key Laboratory of Structural Analysis for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian, China

⁵Ningbo Institute of Dalian University of Technology, Ningbo, China

⁶Department of Mechanical Engineering, Northwestern University, Evanston, IL, USA

⁷School of Biomedical Convergence Engineering, College of Information and Biomedical Engineering, Pusan National University, Busan, Republic of Korea.

⁸Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA

⁹State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai, China

¹⁰Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA

¹¹Department of Chemical Engineering, Northwestern University, Evanston, IL, USA

¹²The Institute of Materials Science and Engineering, Washington University, St. Louis, MO, USA

¹³Department of Pathology, Northwestern University, Evanston, IL, USA ¹⁴Department of Biomedical Engineering, Washington University, St. Louis, MO, USA

¹⁵Departments of Civil and Environmental Engineering, Northwestern University, Evanston, IL, USA

¹⁶Department of Chemistry, Northwestern University, Evanston, IL, USA

¹⁷Department of Electrical Engineering and Computer Science, Northwestern University, Evanston, IL, USA

¹⁸Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Evanston, IL, USA

About Pusan National University
Pusan National University, located in Busan, South Korea, was founded in 1946, and is now the no. 1 national university of South Korea in research and educational competency. The multi-campus university also has other smaller campuses in Yangsan, Miryang, and Ami. The university prides itself on the principles of truth, freedom, and service, and has approximately 30,000 students, 1200 professors, and 750 faculty members. The university is composed of 14 colleges (schools) and one independent division, with 103 departments in all.    

Website: https://www.pusan.ac.kr/eng/Main.do

About Assistant Professor Min-Ho Seo
Dr. Min-Ho Seo received his B.S. degree (Magna cum laude, 2011) in nanomechatronics engineering from Pusan National University and his M.S. and Ph.D. degrees (2013 and 2018, respectively) in electrical engineering from the Korea Advanced Institute of Science and Technology (KAIST). Between 2018 and 2019, he was a postdoctoral research fellow at the Information and Electronics Research Institute at KAIST, following which from 2019 until 2020, he joined the Center for Bio-integrated Electronics at Northwestern University in USA as a postdoctoral researcher.

Since 2020, he has been affiliated with the School of Biomedical Convergence Engineering, Pusan National University, where he works as an assistant professor. His research interests include nano/microelectromechanical systems, biomedical devices and electronics, flexible and wearable electronics, and physical, chemical, hydrogen, and optical sensor devices and electronics.

Lab website: http://sites.google.com/view/mhseogroup

ORCID ID: Prof. Min-Ho Seo:0000-0002-9990-9227