Novel materials play an important role in our lives and one such material is polymers. Polymers are materials made up of long, repeating chains of molecules packed into individual units called monomers, and they are pervasive. As examples, DNA is a type of polymer made up of nucleotide monomers and starch is a polymer made up of many sugar molecules. Moving beyond our bodies, polymers are also present in rubber tires, anti-stick pans (widely known Teflon® is made up of polytetrafluoroethylene), and contact lenses (silicone hydrogels).
Tapping into advances in materials engineering, new classes of polymers have emerged for non-traditional applications such as bioelectronics, an inter-disciplinary field that exploits electrical engineering for biological applications including sensing, diagnosis, and therapeutics. In recent years, a variety of polymer-based bioelectronics have been produced for areas like peripheral nerve stimulation and heart rate monitoring. Here, we focus on recent progress of the use of polymers for wearables and biomedical applications.
Polymers for wearables
The global wearable electronics market is estimated to be worth $116 billion in 2021. Wearable technology is an emerging trend that integrates electronics into daily activities, including the monitoring of physiological signals and even providing early indications of illnesses. Wearables are expected to play an increasing role in personalized disease prevention and health promotion as well.
Piezoelectric materials are popular for use as textile wearable sensors due to their self-powering property that can convert body motions like respiration and limb movements into electrical signals. They are also relatively light and can be blended with textiles for wearables. There are two main classes of materials that are used for piezoelectric textile fabrication—inorganic ceramics and organic polymers. The former provides superior electromechanical properties, but it is brittle, rigid (non-conformable to body shapes), and can be toxic to users. The latter has inferior piezoelectrical properties, but possesses excellent mechanical flexibility and biocompatibility.
Yuanjie Su, of the University of Electronic Science and Technology of China, and colleagues recently synergized the advantageous properties of both classes of materials by blending inorganic ceramics into an organic polymer matrix. Inspired by the organization of muscle fibers, the team created a polydopamine-based thin linkage between inorganic ceramic fillers (barium titanate oxide, BTO) and polymer matrix (polyvinylidene fluoride, PVDF) to improve the mechanical and piezoelectrical properties of the composite material. This is achieved through weak electrostatic attractions called van der Waals forces between polydopamine (formed through dopamine and BTO nanoparticles interactions) and the PVDF polymer matrix.
“The incorporation of inorganic piezoelectric ceramics into an organic polymer matrix provides a creative approach to synergize the advantageous features of both organic and inorganic piezoelectric materials. However, the large mismatch of mechanical moduli between the two phases imposes a tremendous challenge to deliver the mechanical stress onto the embedded ceramic fillers. In this work, we explored modification by polydopamine to enhance and optimize piezoelectric properties by both experimental and theoretical investigations of the mechanism and functionalities,” says Jun Chen, PhD, assistant professor at the University of California, Los Angeles.
To test the compatibility of their materials for wearables, the team employed a variety of techniques to analyze how their polymer would react to mechanical stresses, stress distribution, its capacity to generate electrical signals, and mechanical durability. Different methods measuring similar properties were used to demonstrate the novelty of their polymer compared to unmodified polymers. This was an important step before they could use the material reproducibly for wearable applications.
First, making use of electron microscopy, the authors found that the embedded BTO fillers could generate piezoelectric potential in response to external stress forces and the polydopamine coating could facilitate uniform transfer of stress forces at the interface between BTO filler and PVDF matrix, which was confirmed by phase-field simulation. On the other hand, in unmodified polymer fibers, the applied stresses were primarily concentrated on the ends, which was not ideal as this would lead to uneven signal capture. The team then measured the sensitivity of the fibers in response to mechanical forces and found that the modified fibers provided a sensitivity of 3.95 Volt (V)/Newton (N), which was close to double to that of unmodified fibers (2.26 V/N). This is critical to generate sufficient electrical signals for detection and monitoring. Finally, cyclic loading of 7,400 cycles also revealed that the output voltage declined by less than three percent, demonstrating excellent mechanical durability.
With the material properties characterized and optimized, the team went on to assess their composite polymer materials for interfacing with different mechanical signals from the body. The first application they started with was to measure wrist pulse, which is commonly used to diagnose for cardiovascular diseases. The material was able to distinguish between heart rates when a person is resting and exercising with fast response time of less than 0.1 second, suggesting the utility of the material to measure heart rate for a variety of activities. Lately, the team also integrated advanced material design with neural network learning to enhance cardiovascular monitoring.
“This work not only sheds light on the fundamental understanding of surface modification effect on the piezoelectric properties of nanocomposites, but also offers a promising route toward designing high-performance piezoelectric fiber for wearable bioelectronics. Wearable technologies can enable the change of the current reactive and disease-centric health care system to a personalized model with a focus on disease prevention and health promotion. It will conquer the medical field in the era of the Internet of Things and promote health care transformation, where it will make its greatest impact,” adds Chen.
Polymers for wound monitoring
There is a huge unmet clinical need in deep wound monitoring. While most complications such as bleeding and infection occur post-operation, timely detection of these problems is limited as clinical approaches rely on non-specific signals like body temperature and skin color, which also appear only at severe stages. While the use of imaging modalities like ultrasound can be used to detect complications, they can only be done in a clinical setting with trained personnel.
To address this clinical gap, Viveka Kalidasan, of the Department of Electrical and Computer Engineering, National University of Singapore, and colleagues invented wireless sensing sutures made up of multifilament sutures functionalized with the conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS). This novel polymer provides wireless sensitivity while retaining mechanical flexibility.
The entire system consists of three components. First, a non-resorbable PEDOT:PSS (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate) treated with dimethylsulfoxide (DMSO) was chosen as the conductive polymer as it has the highest reported conductivity for solution-processed polymers and good biocompatibility and biostability. It was also coated with a thin dielectric layer of parylene-C for electrical insulation. Second, a battery-free electronic sensor. Third, a radiofrequency system to transmit and receive wireless signals. This integrated platform is able to detect periodic variations in signal amplitude indicative of small tissue motions and a large decrease in signal amplitude that indicates suture breakage.
Before using their material for applications, the team also carried out extensive characterization to show that the PEDOT:PSS coating was uniform throughout the whole length and was mechanically durable for use in surgical knots. Notably, as different materials could be used in medical sutures, the team also demonstrated that their protocol could be applied across various multifilament materials like silk, cotton, and vicryl to create bioelectronic sutures.
In deep wounds, post-surgery complications such as gastric leakage (application in gastric typing) and suture breakage can occur and adversely affect patient recovery. It is paramount to be able to detect complications as early as possible. Using a porcine model, the team showed that their wireless suture platform was able to detect bioelectrical changes induced by infection of artificial gastric fluids within 10 minutes of injection. Their system could also detect for suture breakage wirelessly without visual access to the surgical site, a feat that has not yet been achieved.
During surgery, deadly bacterial infection can also happen. The team further functionalized their electronic sensor with a DNA-based hydrogel that breaks down upon exposure to deoxyribonuclease secreted by pathogenic microbes. In the event of an infection, there was a change in capacitance for timely detection of bacterial contamination in deep wounds.
“The main novelty in this work is a way to convert a surgical suture into a wireless sensor. To do this, we coated a medical-grade suture with a conductive polymer and combined it with radio-frequency identification (RFID) technology to operate it in a battery-free and wireless manner. We think that this strategy could be also used to functionalize other types of passive medical devices, ranging from gauze, stents, and bone plates, to make them ‘smart.’ This could empower patients to be able to monitor the healing progression of their wounds, even when they are discharged from the hospital,” says Dr. John Ho, assistant professor at the National University of Singapore.
“We are now working with gastrointestinal surgeons to evaluate the sensitivity and specificity of the sensor for monitoring deep surgical complications, such as wound infection and anastomotic leakage. We envision that such sutures may be able to detect these complications early and lead to better outcomes for patients recovering from surgery.”
With continual progress in material sciences, more polymers with novel molecular structures and properties are expected to be synthesized. This will rapidly expand their range of applications in our daily lives. For instance, in the case of bioelectronics, the creation of resorbable polymer materials would be clinically useful as they can be eliminated from the body once they complete their functions. Note that impactful applications of polymers in bioelectronics also depends on sensor technology to transmit and receive signals, and the use of machine learning approaches to effectively distinguish signals. When these technologies go hand in hand, we can expect these powerful materials to improve disease sensing, monitoring, and treatment.