Soft electronic materials for epicardial devices

Kevin Lim1, Sunny Kim*

1
Dauegu Internaltional school, Korea

*To whom correspondences should be addressed.

E-mail: [email protected]

Abstract
Heart failure is a widespread health concern. A person with a heart failure has 5 years shorter life expectancy

compared to a person who has a cancer. Specifically, myocardial disease is usually involved with a treatment

accompanied by an electrical conduction system. To alleviate the physical burden to heart due to ventricular pacing,

epicardial electronic system made of soft and elastic materials is needed. Newly developed materials are promising

candidates to develop an epicardial system that could detect electrical signals of heart rapidly without hindering

the physical movement and functions of heart even after few weeks. Multifunctional epicardial system that

monitors electrical conduction of epicardium surface and stimulate epicardium simultaneously could be a

powerful tool to diagnose and treat myocardial disease. In this review, we discuss candidate materials for novel

epicardial sensing/stimulation systemthat matches similar mechanical properties of heart.

been used for stable electrical performance, guaranteeing the long-term usability. However, conventional rigid

system causes physical burden to epicardium when heart is rapidly expanded or contracted during daily lives. This

mechanical mismatch decreases the bioelectronic performance. The conventional technologies are not suitable to

be utilized as wearable and implantable bioelectronics because their mechanical stiffness can induce side effects.

For example, the rigidity of a wearable device mounted on the skin evokes discomfort and skin irritation (Wu et

al, 2019). Because stiff and flat electronics cannot intimately follow the contour of soft and curvilinear skin, the

pressure is concentrated in a localized area, and friction between the device and the skin may result in allergic

reactions. Moreover, rigid and brittle bioelectronic systems cannot make conformal contact with soft and

curvilinear skin, lowering the bioelectronic performance owing to high impedance and low signal-to-noise ratio.

Besides wearable bioelectronics, the rigidity of implantable bioelectronics can cause inflammatory reactions,

particularly in their long-term implantation (Berggren et al, 2007). For this reason, commercial biventricular pace-

maker could not be implanted directly on heart due to rigidity. Instead, it is generally implanted under the skin. In

addition, unlike conventional wearable and implantable bioelectronics that consist of metal and/or inorganic

materials, biological tissues are hydrophilic, ion rich, and fluidic. This difference in chemical compositions limits

the long-term biocompatibility and performance of bioelectronics. To overcome this issue, there have been many

progresses in material research to realize the mechanically compatible epicardial bioelectronics system. One of

promising materials is an elastomeric material which is suitable for constructing a conformal interface with soft

and curvilinear biological tissue due to its intrinsically deformable property. Intrinsically soft electronic systems

whose mechanical properties are similar to those of human tissue can be developed using functionalized

elastomers. Elastomers can be functionalized by adding appropriate fillers (Figure 1), either nanoscale materials

or polymers. Conducting or semiconducting elastomers synthesized and processed with these filler materials can

be applied to the fabrication of soft integrated electronic devices. Recently, device components such as sensors,

stimulators, power supply devices, displays, and transistors have been developed in a deformable form.

In this review, we categorized the advanced soft materials as listed below.

 Soft elastomeric conductor: soft conductive materials consist of elastomer and conductive filler

 Tissue-like low modulus materials: Hydrogel and its conductive composite

contact with tissue surface to form high quality interface between biotic-abiotic interactions. The softness of bio-

implantable system is a critical factor to operate such systems on curvelinear surfaces of human tissues. Many

researchers have been studied soft and elastic materials to develop soft bio-implantable system for a long time.

Recently, elastomer and hydrogel have been highlighted as promising materials due to their superior mechanical

properties and tunability. Although further researches to optimize those materials are needed, mechanical and

electrical performance of current bio-implantable system using elastomer and hydrogel will be tremendously

enhanced in the future.

Elastomer

An elastomer refers to an elastic polymer whose intermolecular force is weak, thus having both elasticity and

viscoelasticity. According to IUPAC, it is more intuitively expressed as a polymer that has “rubber-like elasticity”.

Elastomer mainly consists of long polymer chain with weak physical or chemical bonds, providing dynamic

movements to polymer chains when it is stretched. Elasticity is mechanical property to recover its shape under

external strain. In macro-scale, the broken weak bonding under strain could reform each other due to elasticity.

Elastomers can also have dynamic mechanical or chemical properties depending on the intermolecular force and

the interaction between polymer chains. For example, strong intermolecular force and less entanglement of

polymer chains of elastomer show the mechanically tough and less elastic. Conversely, if the intermolecular force

is weak and the polymer chains are entangled severely, the elastomer is mechanically soft and elastic. Generally,

elastomer is an insulator so that it can be used as stretchable encapsulation layer of bio-implantable system.

Elastomer/Carbon-based materials

Carbon-based nanomaterials show both mechanical flexibility and highelectrical conductivity. They can be

dispersed in an elastomeric matrix, thereby serving as filler materials in nanocomposite. There are several types

of carbon-based nanomaterials, which can be classified into different shape of dimension such as 0-dimension, 1-

dimension, 2-dimension (Figure 1). The 0-dimensional carbon materials however are difficult to be utilized as

filler materials because they cannot form a percolation network due to their shape and cytotoxicity. As a result,
only 1-demensional or 2-dimensional carbon materials are considered for soft nanocomposite. A typical example

of 1-dimensionalcarbon material is carbon nanotube (CNT), which has a shape of fiber. It is well-known as a

cytotoxic material when inhaled, but no severe cytotoxicity is shown when it is embedded within an elastomer

matrix. A previous work studied the cytotoxicity of the nanocomposite containing CNT on a lung tissue in vitro

(Wohlleben et al, 2012). According to this report, CNT nanocomposite showed high cell viability because CNTs

are fixed in the elastomer matrix of thermoplastic polyurethane (TPU). Because the CNTs do not contact with

outside of the nanocomposite, no cytotoxic effect of CNTS is applied onto cultured cells on surface of the

nanocomposite. The researchers also demonstrated the CNT nanocomposite used as injectable and conductive

cardiac patches (Wang et al, 2021). They showed the electrical performance of CNT nanocomposite related to

electrocardiogram (ECG) measurement and biocompatibility.

Another typical carbon-based nanomaterial shaped in 2-dimensional structure is graphene. Graphene is a sp2

hybridized carbon atoms arranged in a single-layered honeycomb structure. Graphene is transparent because it is

synthesized in a film with single-atom thickness (Muñoz et al, 2013). Due to larger surface area, the 2-dimensional

structure provides improved physical contacts within elastomer compared to 0-dimensional materials so that it

could enhance the electrical property of nanocomposite. Moreover, the 2-dimensional structure provides freedom

of movements in the elastomer so that it can be used as sensitive mechanical sensors for bio-physiological signal

detection (O’Driscoll et al, 2021).

Elastomer/metallic materials

Similar to carbon materials, metal nanomaterials have various shapes such as 0-dimension, 1-dimension,

and 2-demension. Metal nanomaterials have extraordinary electrical conductivities (Naghdi et al, 2018). Although

general form of metal is stiff and heavy, which are not compatible to soft bioelectronics, metal nanomaterials are

flexible and light. Therefore, they can form soft and conductive nanocomposites when they are mixed with

elastomer. As illustrated in the above, 1-dimensional or 2-dimensionalmetal nanomaterials have been widely used

for conductive nanocomposites. Among those materials, silver nanowire (AgNW) is most widely used as 1-

dimensional conductive filler. Choi et al. showed the AgNW-SBS nanocomposite (SBS:Poly(styrene-butadiene-

styrene) to fabricate the mechanically integrated epicardial patch to detect an abnormal phenomenon of ventricles

and to stimulate the ventricles (Park et al, 2017). As a 2-dimensional filler, Ag flake is also widely used as a filler

material for nanocomposite due to its high stretchability and high conductivity for bio-implantable system. Due
to cytotoxicity of silver, another research groups have covered the Ag surface with inert metal to improve

biocompatibility (Choi et al, 2018).

Conductive polymer

In pursuit of making high-performance flexible devices, scientists have researched for new desirable materials

that are cost-effective and light-weight as well as showing remarkable electrical properties. Conducting polymer

(CP) is an organic material that successfully meets these conditions. The intrinsically conducting polymers provide

both high electrical performance and mechanical flexibility. These unusual properties have attracted considerable

interests in material scientists. CPs are often termed as conjugated polymers because they possess alternate single

and double bonds along the polymer chains. The conductivity of CPs is dominantly affected by their delocalized

double-bond arrangements. The well-known CPs are polypyrrole (PPy), polyaniline (PANI), poly(3,4-ethylene

dioxy thiophene) (PEDOT) and polynaphthalene (PN). Basically, CPs have insulating behavior in their pristine

state; however, post-treatments by using dopant and acid could provide high electrical conductivity. CP could also

be functionalized with biocompatible molecules, imparting biocompatibility to sensor and electrical stimulator of

bio-implantable electronic system.

Tissue-like, low modulus materials

electronic systems. Compared to rigid materials such as metal or flexible polymers, elastomer has lower modulus

and higher stretchability. The modulus of elastomer is in the range of hundreds of kilo- to sub mega-pascal.

However, the modulus of organ tissue is much lower, which is in a range of sub kilopascal. Therefore, hydrogel

has been actively researched as a material that can form very similar mechanical compatibility between abiotic-

biotic interfaces due to its low modulus property (Sharma et al, 2020).

Hydrogel

Hydrogels are gel-like materials that consist of hydrophilic polymer network embedding the large amounts of

water contents in the matrix. It includes covalent cross-linking, ionic interactions, and physical entanglement. Due
to their unique structure, mechanical characteristics such as modulus and deformability are similar to those of

biological soft tissues. Also, hydrogels have drawn attention as good candidate materials for biomedical

applications due to its biocompatibility.

Three-dimensional cross-linked hydrophilic polymer networks are expanded and contracted reversibly in water

and retain large volume of liquid in swollen state. They may perform dramatic volume transition in response to a

variety of physical and chemical stimuli (Dolbow et al, 2004), such as temperature, electric field (Jabbari et al,

2007), light (Liu et al, 2013) and organic solvents. Drastic chance of volume in response to the changes in the

external environment of the hydrogel could provide different electrical and mechanical properties. A hydrogel can

be stretched to several times longer than its initial length and recovered elastically. Its elastic moduli could be

tuned from 1 kPa to 100 kPa, or even beyond this range for different applications. To provide toughness in

hydrogel, dual or triple network formation have been studied by combining different types of polymer networks

(Li et al, 2021). Although hydrogels have ionic conductivity via solutes in water, challenging challenge is still

remained to achieve high conductivity for operating electronic device. To enhance the electrical performance,

composite technology could be used as introduced in next section.

Conductive hydrogel composite

Similar to elastomer, 3-dimensional hydrogel network imparts the softness to nanocomposite. Meanwhile, the

electrical properties of nanocomposite are dominantly determined by conductive fillers. There are several

strategies to enhance electrical performance and softness of hydrogel based nanocomposite. Lim et al. presented

material and device strategies to forma tissue-like, quasi-solid interface between wearable bioelectronics and

human skin. They used the hydrogel as mass permeable media to transport molecules using its intrinsic nature of

swelling in the fluidic environment (Lim et al. 2021). When the hydrogel composite swelled in the bodily fluids,

the hydrogel composite show both electrical conductivity of conductive fillers and ionic conductivity of small

molecules in water contents. In other words, the electrical performance of hydrogel composite could be enhanced

in biological environments containing many ionic molecules in biofluids. Another strategy to enhance the

conductivity of hydrogel composite is controlling the expansion of polymeric network (Ohm et al, 2021). In a

previous work, the conductivity of hydrogel-Ag flake composite was improved through the dehydration process

of hydrogel network, creating high percolation conductive pathways in the hydrogel matrix. In this manner,

hydrogel is another promising candidate as a matrix of nanocomposite that shows high electrical conductivity and
mechanical property compatible to soft bio-implantable electric system.

Conclusion
In this review, we discuss the promising soft materials of next-generation bio-implantable electronic device. First,

we introduce elastomeras a basic material for stretchable and flexible electronics. To provide the electrical

conductivity, various conductive nanofillers in different dimensions are addressed to realizeconductive

elastomericnanocomposite. Also, conducting polymers that have intrinsic flexibility and conductivity are

introduced as low-impedance, biocompatible materials for soft bioelectronics devices. Another promising material

is conductive hydrogel composite, which has very low modulus similar to those ofbiological tissues. Both

electrical conductivity of filler and ionic conductivity of bio-fluid in swellingstate of hydrogel matrix allow

superior electrical performance of hydrogel nanocomposite. The soft nanocomposites integrated with

nanomaterials as filler and elastomer/hydrogel as matrixshow potential to open a new pathway in high-

performance epicardial electronic system that improve accuracy, stability, and long-term usability in diagnosis

and treatment of heart diseases.

Acknowledgements
I would like to thank Sunny Kim for his guidance, encouragement during process of this review, and Kevin for
edits of writing throughout the writing.

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Figures

(Figure 1. Functionalizing elastomers with functional fillers for intrinsically soft materials)

(Figure 2. Schematic showing structure of hydrogel)