Biodegradable Magnetoelectric Paper Personalizes Bioimplants

Abstract

Bioelectronic implants delivering electrical stimulation offer an attractive alternative to traditional pharmaceuticals in electrotherapy. However, achieving simple, rapid, and cost-effective personalization of these implants for customized treatment in unique clinical and physical scenarios presents a substantial challenge. This challenge is further compounded by the need to ensure safety and minimal invasiveness, requiring essential attributes such as flexibility, biocompatibility, lightness, biodegradability, and wireless stimulation capability. Here, a flexible, biodegradable bioelectronic paper with homogeneously distributed wireless stimulation functionality for simple personalization of bioelectronic implants is introduced. The bioelectronic paper synergistically combines i) lead-free magnetoelectric nanoparticles (MENs) that facilitate electrical stimulation in response to external magnetic field and ii) flexible and biodegradable nanofibers (NFs) that enable localization of MENs for high-selectivity stimulation, oxygen/nutrient permeation, cell orientation modulation, and biodegradation rate control. The effectiveness of wireless electrical stimulation in vitro through enhanced neuronal differentiation of neuron-like PC12 cells and the controllability of their microstructural orientation are shown. Also, scalability, design flexibility, and rapid customizability of the bioelectronic paper are shown by creating various 3D macrostructures using simple paper crafting techniques such as cutting and folding. This platform holds promise for simple and rapid personalization of temporary bioelectronic implants for minimally invasive wireless stimulation therapies.

A research team, jointly led by Professors Jiyun Kim, Chaenyung Cha, and Myoung Hoon Song from the Department of Materials Science and Engineering at UNIST, has unveiled the world's first flexible, biodegradable bioelectronic paper with homogeneously distributed wireless stimulation functionality for simple personalization of bioelectronic implants. These innovative materials are made from nanoscale functional materials, and thus can be further customized using simple methods, such as rolling, cutting, inward folding, and outward folding without losing functionalities. The research team expects that these results with unprecedented design flexibility can lay a foundation for the low-cost, simple, and rapid personalization of temporary bioelectronic implants for minimally invasive wireless stimulation therapies.

Implanted electrical stimulation devices are crucial for promoting neuronal activity and tissue regeneration through electrical stimulation. Therefore, these devices are essential for treating various neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. However, most of the state-of-the-art bioelectronic implants require rigid and bulky electronics that are mechanically incompatible with the delicate structure of nerves and other tissues, making it difficult to freely change into various sizes and shapes in real time. In addition, the need for wire connections, battery replacement, and post-treatment removal surgeries can raise the risk of infection and make clinical treatments complex.

In this study, the research team successfully developed a flexible, biomimetic, lightweight, and biodegradable bioelectronic paper that can be cut and tailored post-fabrication while retaining functionalities, allowing for simple and rapid production of bioelectronic implants of various sizes, shapes, and micro- and macro-structures.

First, they synthesized magnetoelectric nanoparticles (MENs) that facilitate electrical stimulation in response to external magnetic field. The synthesized nanoparticles take the form of 'Core@Shell' structure that couples magnetostrictive core that transduces magnetic field into local strain and piezoelectric shell that transduces strain into electric field. By integrating MENs into electrospun biodegradable nanofibers (NFs), they produced a paper-like, biodegradable, porous wireless electrostimulator. In vitro experiments further demonstrated the material's ability to provide wireless electrostimulation and promote neuronal activity simultaneously.

"The developed material offers personalized treatment options tailored to individual needs and physical characteristics, simplifying treatment processes, enhancing flexibility, and versatility in electrical stimulation-based clinical applications," says Postdoctoral Researcher and First Author Jun Kyu Choe.

The fabricated material is as flexible and lightweight as paper. It can be closely attached along complex surfaces, like the curved surface of human brain models. Notably, it also can be cut into arbitrary shapes and scales, while retaining its function. Furthermore, it showed exceptional flexibility enough to manufacture a cylindrical nerve conduit to regenerate nerves, with a demonstrated bending radius of 400 µm.

According to the research team, "This work presents a promising strategy for the development of flexible and biodegradable wireless bioelectronic implants that can be simply customized for various clinical and physical circumstances." They further noted, "The combination of nanoscale magnetoelectric and biodegradable fibrous materials offers advantages over traditional system-level wireless electronic devices that rely on intricate assembly of bulky components that cannot be redesigned post-fabrication."

"The bioelectronic paper, in principle, can be simply customized to organ-scales of several tens of centimeters or miniaturized to sub-micrometer scales for minimally invasive operations, as the magnetoelectricity or microstructure does not depend on its scale." noted Professor Kim. "Overall, our bioelectronic paper with facile and broad applicability, could open up a new scheme toward minimally invasive, and biodegradable wireless bioelectronic implants."

The study, involving Dr. Jun Kyu Choe, Dr. Suntae Kim, and Dr. Ah-young Lee as first authors, was officially published in Advanced Materials on May 2, 2024. Their findings have been selected as an Inside Back Cover feature. The research received support from the National Research Foundation (NRF) of the Ministry of Science and ICT.

Journal Reference

Jun Kyu Choe, Suntae Kim, Ah-young Lee, et al., "Flexible, Biodegradable, and Wireless Magnetoelectric Paper for Simple In Situ Personalization of Bioelectric Implants," Adv. Mater., (2024).

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