A biodegradable cardiac electrotherapy device paving the way for autonomous transient implants

Abstract

In a recent article published in Science, Choi et al. introduce an innovative approach to cardiac rhythm control through a newly developed, temporary, wireless, bioresorbable pacemaker.¹ This pacemaker operates in a closed-loop fashion, dynamically adjusting pacing parameters to match metabolic demands of the heart while ensuring mechanical robustness and compatibility with magnetic resonance imaging.

The system comprises three implantable, bioresorbable components, a pacemaker, an anti-inflammatory drug-eluting patch, and a power harvesting unit. Additionally, it includes three skin-interfaced components, a set of physiological sensors, a wireless power transfer module, and a haptic actuator. An external, handheld device with a software application is used for data-management and control (Figure 1).¹ After patient recovery, the skin-interfaced devices, including sensors are easily removed.

The motivation behind the use of biodegradable implantable sensors stems from the necessity to monitor and treat postoperative complications effectively. Such implants mitigate risks associated with nonbiodegradable alternatives, including bacterial colonization and infection, as well as the challenges associated with their removal, particularly in sensitive areas. Clinical trials will determine the accuracy of pacing and electrocardiogram (ECG) recordings with skin-interfaced sensors. It also remains to be found whether combinatorial sensor-actuator transient implants with biodegradable sensors will be more accurate since implantable sensors may provide more accurate data compared to skin-interfaced sensors.

Biodegradable sensors also offer opportunities for minimally invasive and temporary monitoring and therapeutic interventions, enabling real-time tracking of physiological parameters and targeted delivery of therapeutic agents or electrical stimulation to specific areas of the body.² Unlike skin-interfaced sensors, implantable biodegradable sensors do not need to withstand the movements of the body, and they minimally infringe on them. They are also less cumbersome, and they are comfortable for patients.

Although it is advantageous to have implants that can degrade and disappear, their degradation can lead to a inflammatory reaction. Uncontrolled, it becomes chronic and leads to fibrous tissue encapsulation of the implant and sensor and hindrance of their function. Therefore, the fibro-inflammatory reaction needs to be properly kept under control. Choi et al.¹ used an anti-inflammatory steroid (dexamethasone acetate)-eluting patch. Alternative strategies that may be considered in the future are using anti-inflammatory drug release, implant coating, micro- and nanopatterning, and surface functionalization, which may simplify the implant design. Because the use of stiff materials leads to the activation of integrin and the release of transforming growth factor-beta 1 which drives fibrous tissue formation, the combination of the release of integrin-binding inhibitory molecules and soft coating can therefore reduce the thickness of the forming fibrous tissue encapsulation.² The use of bioresponsive materials that can release active agents when triggered by changes in the local microenvironment or by externally applied stimulation³ may also help to control tissue reactions and maintain the function of the implant and sensor, in future.

Continuous data streaming from sensors may provide early warnings of potential health issues, although challenges exist in ensuring timely transmission to the handheld device. Consequently, responsibilities of the patient and the device manufacturer can be difficult to differentiate. Artificial intelligence (AI) holds promise for automating data processing, but practical implementation requires further exploration. Furthermore, the sense of well-being of certain types of patients may become affected due to their obsessive involvement in the data retrieved.

While initially demonstrated to be effective for postsurgical recovery from bradycardia in animal and ex vivo models, the closed-loop system presents broader clinical potential, particularly in delicate areas like the central nervous system, where small damage can lead to devastating results. In these tissues such as the brain, biostable implant and sensor removal can lead to brain injury and, therefore, the use of biodegradable sensors for temporary applications, for example, monitoring pressure, temperature, and hydration can be of great clinical value.

In this work,¹ ECG electrodes were used to collect signals, and skin-module was a printed circuit board encapsulated by silicone elastomer. Sensors can be fabricated using different methods such as three-dimensional (3D) printing, transfer-, screen-, aerosol, laser- and inkjet printing, photonic sintering, thermal growing, sputtering, micromolding, and combination of fabrication techniques, for example, combination of aerosol printing with photonic sintering.⁴ In addition, the integration to living components can be added, such as using sensing cells or microorganisms. Biomaterials used in these sensors comprised biodegradable polymers, metals, and nanosilicon.⁴ Recently, bioactive glass was added to this armamentarium.⁵ The combination of smart materials that have self-awareness, self-healing/repair, stimuli-responsive, and self-actuating will enable developing autonomous implants.

This study lays the groundwork for autonomous transient implants capable of sensing and responding to physiological needs, such as matching cardiac pacing to metabolic demands of the heart. Although this system integrates sensing, actuating, and communication aspects, there are still technology components that can be integrated such as AI and cloud computing, which are currently available, or those that become more feasibly available to integrate in future. The system components can be a part of an Internet of Medical Things. Healthcare system will be very different then, and will integrate information from all implants and devices.

Mladen Veletić: Investigation (lead); writing—original draft (lead); writing—review and editing (equal). Nureddin Ashammakhi: Conceptualization (lead); supervision (lead); writing—review and editing (equal). Both authors have read and approved the final manuscript.

The authors declare no conflict of interest.

Not applicable.