Having been in academia for almost a decade now, I find myself primarily motivated by the research and development work that can potentially bring real benefit to patients. During my four years as a research fellow at the NUS Wireless Bioelectronics Lab, I had the pleasure of doing such work every day, as I took an abstract idea and turned it into a proof-of-concept for a technology, called WiSe sutures, that might transform the way that clinicians detect post-surgical complications as they happen at the surgical site. Through this behind the paper post, I will spotlight 5 aspects of this research and development journey.
1) From brainstorming to development of WiSe sutures
There are some perks to being one of the first postdocs in a newly formed lab, just like being an early employee in any startup – one gets to brainstorm ideas and set the culture of the lab. When I joined Dr. John Ho’s NUS Wireless Bioelectronics Lab, it was (and still is) a young and dynamic lab that was open and hungry for fresh ideas and perspectives. For a high energy person like me, the environment was an abode of possibilities.
For the first 3 months, I found myself generating 1 idea per week, thinking of ways to marry my materials science expertise to my lab’s wireless capabilities. During one presentation, John chose the word ‘smart sutures’ nestled in the corner of one my slides. The concept of smart sutures was not even the core of my presentation that day, so the words unexpectedly set the path for the next four years. We went on to turn that spark into a proof-of-concept for a technology that may change the way post-operative complications are detected and treated. We named this technology WiSe (wireless sensing) sutures, which is synonymous with “smart” and reflects the capabilities of these sutures.
The clinical need was clear: we wanted to detect surgical site complications in real-time when and where the complications occur and not after severe symptoms arise. To address this need, what is a better candidate to start with than a surgical suture, which sits right at the site of surgery? Earlier work had already pioneered this concept using electronic strips and conductive threads as sensor-integrated sutures, to monitor the wound site [1, 2]. A major limitation, however, remained in wired connections required to enable powering and communications. Our work sought to address these challenges.
We wanted the suture to be able to communicate sensor data to the external world in a wireless and battery-free way. The largest part of such a device is the antenna, and so we decided to convert the entire suture into an antenna with conductive coating. After evaluating many candidates, PEDOT:PSS was found to have the necessary properties, with excellent conductivity, flexible mechanical properties , and well-characterisized biocompatibility and biostability . I optimized the protocol to coat PEDOT:PSS over silk sutures in such a way that the inherent mechanical capability and biocompatibility of a medical grade suture is not compromised.
To isolate the signal from the WiSe suture from environmental reflections, we needed to attach a Schotty diode on the suture, which responds nonlinearly by generating harmonics of the transmit signal. Taking inspiration from cotton pledgets often used during surgery to ease the pressure applied by the suture on tissues, we devised an “electronic” pledget that could be attached on the surgical stitch during suturing. These pledgets also have a resonant circuit and a capacitive sensor that allow the signal of interest to be encoded as resonant frequency shifts – which are isolated from other signal variations arising from factors such as bodily motion. We explored a variety of sensors that could be integrated into this architecture, including bio-responsive hydrogels that could selectively degrade when exposed to certain biofluids to detect complications such as gastric leakage and infection. These pledgets could also measure vital signs like respiration and heart rate
2) Translational aspirations for WiSe sutures
As we developed the technology, I came to appreciate first-hand, the importance of talking to end-users so that our design decisions lead to an outcome that is clinically relevant and actually addresses the pain-points for clincians and patients. Our team met with different stakeholders over coffee and even in operation theatres. We heard their unmet needs and their challenges and considered how our technology might be relevant. One such meeting with Dr. Choong Seng Chong, who is a gastrointestinal surgeon and collaborator on this project, helped us to hone in on using the sutures to detect anastomotic leakage.
One of the most critical procedures of any gastrointestinal surgery like colorectal surgery is anastomosis – a surgical technique used to join two vessel-like tissues. Between 1-30% of post-surgical complications during gastrointestinal surgery are due to the failure of the anastomosis. This results in leakage of intestinal contents into abdominal cavity, increasing mortality by threefold . Anastomotic leakage is often not detected until symptoms such as fever and nausea arise, by which time there is significant risk of sepsis . This clincal need led us to synthesize a peptide hydrogel that could respond to the presence of gastric fluid and informed the design of our animal experiments to demonstrate detection wirelessly.
Over the course of this project, I spoke to almost 200 different stakeholders including clinicians, scientists, senior management in medical device companies, medical device distributors, patients, care-givers. These conversations have shaped in countless ways. For instance, we made sure that the pledgets can be easily attached to the WiSe sutures at the site of surgery during an intraoperative procedure. We also made multi-pledgeting possible, as clinicians suggested that a single sensor might miss complications for larger surgical wounds. For a technology to be clinically relevant, it is necessary for it to be compatible with every stage of the standard clinical work-flow. This project emphasized to me the importance of engineers to talk and listen more to clinicians and other stakeholders in order to be aware of their unmet needs.
3) Importance of a collaborative core team
Crucial to the success of the project was a very interdisciplinary core team in which each member understands other’s strengths and weaknesses. My PhD was in materials science and engineering, while co-first author Yang Xin is pursuing his PhD in electrical and computer engineering, and another co-first author Dr. Xiong Ze has a background in chemistry. I developed methods to fabricate conductive sutures with comparable with medical grade properties. Xin added wireless capabilities to it by designing the system for wireless and powering and sensing platform. Ze devised ways to sensorize the WiSe sutures. We all worked tirelessly to test the system in both laboratory setups and animal wound models. We had complementary skill-sets needed for an interdisciplinary research. We brainstormed together and heard each other’s views before we chalked out the experimental plan for each step in our bench-top and preclinical studies. As the PI, John elegantly connected the dots as both a leader and a mentor. WiSe sutures are a product of different expertise put together to solve an unmet clinical need.
4) Next steps
As we developed the concept into a technology, we have been constantly looking for ways to turn it into a clinical reality. One night, I had a call with a medical device distributor in north America who told me, “Viveka, I’m looking forward to the day WiSe can be a reality. I mean it, because a technology like WiSe could have saved my father, who died of anastomotic leakage after colorectal surgery.” These words drove home to me that my work was more than just a laboratory research project and that real patients today might be waiting for me to make this technology a reality. Our team is working in a number of directions to translate the technology: i) we are designing WiSe sutures that are specific for use in anastomoses, ii) we are extending the range of operation to 10 cm or more for use across a more diverse population, and iii) we are investigating ways to retrieve the sutures after they have served their purpose.
5) Personal satisfaction
I joined Dr. John Ho’s NUS Wireless Bioelectronics lab as a postdoctoral research fellow in Aug 2017. Though I always had translational aspirations, I joined the lab with an open mind. For the past 4 years, from ideation to the development of WiSe sutures, every single day, I found myself doing what I truly believed in and enjoyed. John, the WiSe team, the entire lab and the collaborators have been incredible mentors. Today, I can say that I am a ‘WiSer’ individual – this project has challenged me to grow in innumerable ways as an innovator, as a technopreneur, as a person.
- Kim, D.-H., Wang, S., Keum, H., Ghaffari, R., Kim, Y.-S., Tao, H., Panilaitis, B., Li, M., Kang, Z., Omenetto, F., Huang, Y. & Rogers, J. A. Thin, flexible sensors and actuators as ‘instrumented’ surgical sutures for targeted wound monitoring and therapy. Small 8, 3263-3268 (2012).
- Mostafalu, P., Akbari, M., Alberti, K. A., Xu, Q., Khademhosseini, A. & Sonkusale, S. R. A toolkit of thread-based microfluidics, sensors, and electronics for 3D tissue embedding for medical diagnostics. Nanoeng. 2, 16039 (2016).
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- Rivnay, J., Inal, S., Salleo, A., Owens, R. M., Berggren, M. & Malliaras, G. G. Organic electrochemical transistors. Rev. Mater. 3, 17086 (2018
- P. Kingham, H.L. Pachter, ‘ Colonic Anastomotic Leak: Risk factors, Diagnosis and Treatment’, JACS 28(2), 269-278, Feb. 2009
- Gessier, O. Eriksson, E. Angenete, ‘ Diagnosis, treatment and consequences of anastomotic leakage in colorectal surgery’, Int J Col Dis., 32(4), 549-556, Jan 2017