Biodegradable, Biocompatible, and Implantable Multifunctional Sensing Platform for Cardiac Monitoring

Abstract

Cardiac monitoring after heart surgeries is crucial for health maintenance and detecting postoperative complications early. However, current methods like rigid implants have limitations, as they require performing second complex surgeries for removal, increasing infection and inflammation risks, thus prompting research for improved sensing monitoring technologies. Herein, we introduce a nanosensor platform that is biodegradable, biocompatible, and integrated with multifunctions, suitable for use as implants for cardiac monitoring. The device has two electrochemical biosensors for sensing lactic acid and pH as well as a pressure sensor and a chemiresistor array for detecting volatile organic compounds. Its biocompatibility with myocytes has been tested in vitro, and its biodegradability and sensing function have been proven with ex vivo experiments using a three-dimensional (3D)-printed heart model and 3D-printed cardiac tissue patches. Moreover, an artificial intelligence-based predictive model was designed to fuse sensor data for more precise health assessment, making it a suitable candidate for clinical use. This sensing platform promises impactful applications in the realm of cardiac patient care, laying the foundation for advanced life-saving developments.

Keywords: artificial intelligence; biodegradable; cardiac monitoring; health monitoring; implantable sensor; multifunctional.

Figure 1

Overview of the biodegradable multiplex nanosensor platform for cardiac monitoring. (a) Concept of implantable multifunctional sensors for cardiac monitoring, including sensor implanting for detecting multiple biomarkers: pressure, lactic acid, pH and VOCs, AI-data fusion, results analysis, and degradation. (b1,b2) Flexible and bendable electrodes on polylactic acid (PLA). (c1,c2) Degradation of the sensors after a period.

Figure 2

Performance of the multiplex nanosensor platform. (a) Schematic of the design of the biosensor. (b) OCP measurement and response of the pH biosensor. (c) Stability and selectivity of the pH biosensor after adding glucose and lactic acid solutions. (d) Repeatability and reversibility of the pH biosensor. (e) Electrochemical response of the lactate biosensor. (f) Selectivity of the lactate biosensor. (g) Repeatability and reversibility of the lactate biosensor. (h) Schematic of the pressure sensor design. (i) Pressure sensor response to the different pressure values. (j) Repeatability and reversibility of the sensor in 5.6 kPa. (k) Repeatability and reversibility of the sensor in 12.2 kPa. (l) Schematic of the VOC sensor design. (m) Response of the Zn NPs functionalized with fluorine to hexanol. (n) Response of the VOC sensor array to furfural. (o) PCA to differentiate and identify the different VOCs.

Figure 3

Biocompatibility and cytotoxicity tests using cardiac cells. (a) Shape and morphology of the H9c2(2–1) cardiac cells model. (b) MTT cytotoxicity results. (c) Cell number of the constituent materials after 2 days. (d) Cell number of the sensing materials after 2 days compared to the control. (e) Cell number of the constituent materials after 7 days. (f) Cell number of the sensing materials after 7 days. n = 3. Data are presented as mean values ± SD.

Figure 4

Degradation tests were carried out for the fabricated sensor array. (a1–a4) Degradation of the Mg electrode in SBF at 0, 3, 12, and 24 h accordingly. (b1–b3) Schematic of the degradation of the Mg electrode in SBF. (c1) Beginning of the degradation of PLA. (c2) Degradation of the PLA substrate in SBF after 1 year. Fourier transform infrared (FTIR) diagram of (d) the Zn NPs, a thiol, and their combination. (e) Degradation of the Zn NP-thiol in SBF over time.

Figure 5

Ex vivo validation of the sensor using 3D printed models and AI-model development. (a) Overview of the ex vivo experimentations set. (b) Testing the biodegradable pressure sensor with a 3D-printed silicone heart model. (c) Pressure response with normalized resistance. (d) 3D-printed cellularized cardiac patch. (e) Confocal image showing the three-dimensional self-organization of cardiomyocytes within the printed cardiac patch (Scale bar = 50 μm). (f) Printed cardiac patch was tested with the biodegradable biosensor. (g) Response of the pH biodegradable biosensor using the cardiac patch. (h) Response of the lactate biodegradable biosensor using the cardiac patch. (i) Diversity visualization of the sensor data set. (j) Predictions on the training data set. (k) Predictions on the test data set.