Stretchable biosensors are increasingly crucial for in vivo applications, particularly in cardiology. Current methods, often employing direct ink writing (DIW) with biocompatible inks, suffer from mechanical and electrical hysteresis due to their viscoelastic nature under large strains, hindering reliable recording. This paper addresses this limitation by introducing a novel sponge-like poroelastic silicone composite ink, designed to overcome the drawbacks of existing viscoelastic inks. The poroelastic nature, characterized by reversible compressibility, is expected to mitigate hysteresis. The exceptional softness, comparable to cardiac tissue, promotes gentle tissue interaction. The robust structural integrity, achieved by integrating conductive nanofillers within the porous structure, minimizes the risk of delamination and ensures reliable signal acquisition during repeated cardiac cycles. The study aims to demonstrate the feasibility of rapid custom prototyping using this new material and to evaluate its in vivo performance in a relevant physiological model. The success of this approach would significantly advance the development of advanced biosensors for real-time physiological monitoring and intraoperative guidance.

The literature review highlights existing challenges in creating reliable stretchable biosensors for in vivo applications, particularly in cardiac applications. Conventional lithography-based techniques are complex, while direct ink writing (DIW) with biocompatible and conductive inks offers a promising alternative. However, these existing inks often exhibit viscoelastic behavior, leading to mechanical and electrical hysteresis under large strains. This hysteresis, affecting both sensor sensitivity and long-term stability, hinders the reliable recording of physiological signals, especially in dynamic environments like the beating heart. The authors cite various studies on conductive polymer inks and silicone composite inks containing conductive nanofillers, illustrating the limitations of existing approaches. They also mention challenges associated with delamination from substrates due to differences in material elasticity and interfacial interaction energy. This review establishes the need for a new material with enhanced properties to overcome the shortcomings of existing technologies.

The study involved the development and characterization of a novel sponge-like poroelastic silicone composite ink. This ink comprises a base resin, a dilute resin (Sylgard 184), and polysiloxane-treated hydrophobic silica (SiO2-PS) particles. The ratios of these components were systematically varied to optimize the rheological properties for printability and pore formation. Molecular dynamics (MD) simulations were performed to predict the miscibility of the components and assess the interfacial interaction energy. Rheological properties, including storage and loss moduli, viscosity, and time-dependent changes, were measured using a rheometer. The mechanical properties, including stress-strain curves and hysteresis, were evaluated using a mechanical testing system. Electrical hysteresis and resistance changes under cyclic strain were also measured. Custom biosensor arrays were fabricated using direct ink writing, followed by steam etching to create a porous structure. Conductive Ag flakes were embedded within the pores and plated with Cu and Au for electrical conductivity and biocompatibility. A water-soluble PVA film facilitated handling and temporary support. The study included in vivo experiments using murine and porcine models. Four-dimensional (4D) ultrasound imaging was used to generate 3D models of infarcted heart regions for custom device design. In vivo ECG recording and simultaneous ultrasound imaging were performed to evaluate the biosensor performance in both healthy and infarcted murine hearts. Biocompatibility and biofouling resistance were assessed using cell viability assays and BSA-FITC protein adsorption studies. Histological analysis was conducted to evaluate the inflammatory response to the implanted biosensors. Left ventricular ejection fraction was measured using ultrasound to assess the impact of the biosensor on cardiac function.

The researchers successfully formulated a novel silicone ink with optimized rheological properties for DIW and pore formation. MD simulations confirmed enhanced miscibility of the SiO2-PS particles with the resins. The resultant sponge-like poroelastic material exhibited significantly lower mechanical modulus (E < 30 kPa) than commercial inks (E > 1.11 MPa), comparable to cardiac tissue. This material showed excellent printability, creating microscale features, and a prolonged working time (34h). Notably, the poroelastic biosensors demonstrated substantially reduced mechanical and electrical hysteresis compared to control inks, resulting in low energy loss. In vivo studies showed high-fidelity epicardial ECG recording in healthy murine and porcine hearts. Intraoperative mapping in a murine myocardial infarction model revealed clear ST-segment elevation consistent with the location of the infarction. Simultaneous ultrasound imaging provided real-time validation of the infarction location. The biosensors showed good biocompatibility and anti-biofouling properties and did not significantly affect cardiac function. The low bending stiffness of the devices (<8.0 × 107 GPa µm²) allowed for strong capillary adhesion to the epicardial surface in vivo.

The findings demonstrate the successful development and validation of a novel poroelastic biosensor for simultaneous epicardial recording and imaging. The unique poroelastic properties of the new ink addressed the limitations of existing viscoelastic inks, yielding highly reliable signal acquisition in a dynamic physiological environment. The soft and flexible nature of the devices, coupled with their low hysteresis and robust conformal contact with the heart, minimizes tissue trauma and ensures accurate ECG measurements. The ability to perform simultaneous high-fidelity ECG recording and ultrasound imaging provides a powerful tool for intraoperative guidance during cardiac procedures and for the investigation of cardiac diseases. The study also demonstrates the capability for rapid custom prototyping, enabling adaptation to diverse heart sizes and shapes. The superior biocompatibility and anti-biofouling properties underscore the clinical potential of these devices. The results suggest the feasibility of expanding this technology for long-term cardiac monitoring through chronic implantation and integration with wireless power and data transmission.

This research successfully developed and validated a novel, soft, and highly stretchable poroelastic biosensor for simultaneous epicardial ECG recording and ultrasound imaging. The custom-designed, rapid prototyping approach and the unique properties of the poroelastic material enable high-fidelity signal acquisition in dynamic conditions, potentially revolutionizing intraoperative cardiac mapping and long-term monitoring. Future work may focus on increasing spatial resolution, exploring chronic implantation strategies, and integrating wireless communication for continuous monitoring and data transmission.

While the study demonstrates the potential of the developed biosensors, some limitations exist. The in vivo studies were primarily conducted in murine and porcine models, and further studies in larger animal models and humans are warranted to confirm the findings. The long-term biocompatibility and the potential for foreign body responses need further evaluation through extended in vivo studies. While the anti-biofouling properties were promising, exploring advanced surface modifications could further enhance these characteristics. The current spatial resolution, dictated by the nozzle size, could be improved for higher-resolution mapping.