Bridging the gap — biomimetic design of bioelectronic interfaces

Highlights

• Biomimetic designs can improve the compatibility and efficiency of bioelectronics.

• Biomimetic designs enable seamless biointegration down to the subcellular and molecular levels.

• Properties, form, function, and formation mechanism are cornerstones for biomimetic device designs and implementation.

• Probes resembling neurons and materials assembled through genetic targeting represent new biomimetic design approaches.

Applied bioelectronic interfaces have an enormous potential for their application in personalized medicine and brain-machine interfaces. While significant progress has been made in the translational applications, there are still concerns about the safety and compliance of artificial devices interacting with cells and tissues. Applying biomimetic design principles enables developing new devices with improved properties in terms of their signal transduction efficiency and biocompatibility. Learning from the paradigms of biological architecture, we can define four cornerstones of biomimetics, which can guide designing new bioelectronic devices or providing improved solutions to challenging biomedical problems. Recent progress shows how these paradigms were successfully employed, for example, to create neuron-like electronics and assemble electronic materials in situ onto the cell membranes using genetic targeting.

Introduction

Since the earliest days, humans have had a special admiration for Nature. While our understanding of the physical world progressed steadily throughout the ages, biology observed the biggest explosion in the number of discoveries at the end of the last millennia, and today, the funding for life sciences accounts for nearly half of the US federal research spending [1]. Such enormous progress was enabled by the discoveries and development of techniques that enabled the study and understanding of cellular and subcellular processes [2] up to the molecular basis underlying the existence of life. Only now can we truly appreciate the complex yet elegant biological designs present in Nature from which we can learn and adapt its concepts into our own intelligently designed systems.

It is not by accident that our most significant discoveries in biological sciences coincide with the greatest development in human engineering — digital electronics. Without the technologies that enable computer-based processing of information, we would not be able to look into the cells’ structure or acquire and understand the significance of the information stored in the genome [3]. The newest advances in data processing and analysis, especially in machine learning, enabled new opportunities in microscopy, computational biology, and translational medicine [4]. This co-dependence of technology and biology will inevitably end with the merging of natural and artificial systems. However, such an endeavor remains a formidable task as our current state of engineering does not allow for the seamless integration between those two naturally dissimilar systems.

It is a major direction in biomedical research, especially in bioelectronics, to achieve seamless biointegration on the subcellular levels. The goal of targeting subcellular components is achieving improved efficiency and high specificity of recording and stimulation. Interfaces formed between large electric elements and tissues generate interactions that are prone to cross-talk between many cells and devices that can interface with only a specific part of the cell membrane maximize the interaction specificity. Additionally, targeting subcellular components can provide new modes of biomodulation, for example, directly affecting energy production through the regulation of the mitochondria network. However, developing such solutions remains challenging and requires new approaches to devices’ design.

The biological systems evolved over millions of years to specialize in their respective functions, and while our understanding of such processes constantly improves, it does not seem that we would be able to alter or replace biological structures to make them fit our needs in the near future. On the other hand, we can actively strive to make our electronics more nature-like by intentionally introducing biomimetic structures and design paradigms. Our ultimate goal is to achieve minimally invasive integration through the application of Nature-inspired blueprints and materials. The more similar the structures and less mismatch between their properties — the more biocompatible they become and are less prone to rejection by the biological structure [5]. Proper structural and functional matching would maximize the efficiency of interactions and allow new bioelectronic devices to achieve viability levels that can enable the more delicate and precise study of the physiological process, and which will be adapted to future therapeutical applications as well.

To begin thinking about biomimetic design, we have to consider the specific lessons we can take from Nature on designing and building complex structures (Figure 1). The most important lesson is that biological systems are defined up to an atomic level. Almost every biological structure derives its function from the specific arrangement on the molecular scale. From nucleic acids, through ribosomes, to proteins and protein complexes — a single change can often be introduced that would completely disturb the system. It is, of course, the principle of evolution that the accumulation of changes can enable new functions, but this observation only strengthens the importance of the relationship between the structure and function [6]. Even for the large structures with mineral deposits, such as bone tissue, the material’s distribution is precisely controlled, enabling the properties difficult to achieve using heterogeneous materials. Such properties are enabled by the second principle of biological design, which is the formation of complex three-dimensional assemblies. Structures such as the brain cortex or renal pyramids in kidneys can only perform their function thanks to integrating multiple different cells and forming the appropriate spatial arrangement. Further, observing the lower dimensional biological structures, such as nerve bundles, will reveal the next biomimetic design principle — high-density packing and parallelization. For example, research-grade neural recording and stimulation electronics currently enable hundreds of channels [7,8], and translational efforts utilizing multiple shanks can bring the total number of interfacing electrodes to thousands [9]. However, these approaches remain outmatched by biological structures such as the human optical nerves, which are made of more than a million neuron fibers [10]. Therefore, to enable high-throughput and fidelity in biomimetic electronic applications, we must learn to form and scale-up our designs.

For the complete picture of the biological systems, we cannot forget about the plethora of living behaviors that they display. Growth, replication, motility, regeneration, and self-destruction are all processes that can be replicated in the biomimetic design. Many living behaviors are possible thanks to energy transfer mechanisms, for example, adenosine triphosphate (ATP) dissociation can drive organelles’ movement within the cell or rotation of flagellum for the entire cell propulsion. Driving such processes requires precise control over progressing chemical reactions both in time and space. In our biomimetic designs, we are yet to master the creation of structures operating in this far from equilibrium energy landscape.

Applying biomimetic design concepts can make our materials and electronic systems life-like and improve their compatibility with natural structures. This review will summarize current approaches and directions in electronics research inspired by the biological design paradigms. We will discuss current progress in biomimetic electronics, as well as remaining challenges and future directions.