Functional Bioelectronic Materials for Long-Term Biocompatibility and Functionality

Background

Bioelectronics are expected to detect biosignals and deliver treatment over long periods, but current devices lack long-term stability, biocompatibility and functionality after implantation. The review attributes this to three obstacles. Biological tissues have elastic moduli of 100 Pa to 100 kPa and deform by about 10 to 70%, whereas silicon and metals exceed 100 GPa and break at about 5% strain. Implanted materials trigger a foreign body reaction (FBR) that can enclose the device in a fibrotic capsule and cause failure, and moist, irregular and dynamic tissue surfaces make stable device–tissue interfaces difficult.

How the review is organized

Physical compatibility is treated through flexible electronics, in which thinning increases the bending curvature and lowers stiffness, and stretchable electronics, obtained either by geometric engineering of rigid materials (buckling, serpentine and kirigami structures) or with intrinsically stretchable elastomers, liquid metals and polymer semiconductors. Biological compatibility covers hydrophilic poly(ethylene glycol) (PEG) and zwitterionic coatings, hydrophobic lubricant-infused surface (LIS) coatings, biodegradable polymers, drug delivery systems and immobilized biomolecules. Interfacial compatibility covers inorganic and organic encapsulation layers against biofluids, adhesives classified as mussel-inspired, bioarchitecture-based and slug-inspired tough adhesives, and intrinsic self-healing insulators, conductors and semiconductors.

Scope of the review

For each strategy the review describes representative studies with their device structure, test model and reported values, including rat, mouse, pig and canine implantation, porcine skin models and accelerated soak tests. Table 1 lists encapsulation materials with deposition method, thickness, test temperature, results and projected lifetime at 37 °C; its column layout is not preserved in text extraction, so its values are not used here. A final section summarizes remaining limitations for commercialization.

Main points of the review

For physical compatibility, the review describes a silicon nanomembrane array of 2016 transistors with a total thickness of 75 μm that mapped cardiac activation on the epicardial surface of a pig, and soft subdural implants in rats whose ladder-walking performance was indistinguishable from sham animals after 6 weeks, whereas rats with stiff 25 μm polyimide implants showed motor deficits at about 1 to 2 weeks. A hydrogel hybrid probe whose modulus changes by 3 orders of magnitude on swelling recorded neural signals with a stable signal-to-noise ratio in the mouse ventral hippocampus for six months. In a kirigami patch stretched by 282.5%, the maximum local strain stayed below 3.7%, and a permeable liquid metal fiber mat kept an LED lit at 2000% strain.

For biological compatibility, a zwitterionic poly(MPC)-coated continuous glucose monitor reduced inflammation within 8 days in a mouse subcutaneous model and tracked blood glucose without recalibration. A LIS coating on neural probe electrodes produced around 86% fewer impulses during insertion and extended the signal detection period from 8 to 16 weeks compared with bare electrodes. A biodegradable wireless drug-delivery device degraded completely in the canine brain after 10 weeks, an iontophoretic hydrogel patch delivered a model drug to 630 μm in porcine skin compared with 350 μm by diffusion, and antimicrobial peptides immobilized by initiated chemical vapor deposition showed over 97% antibacterial efficacy against Escherichia coli and Staphylococcus aureus in vitro. The review also notes limitations: PEG auto-oxidation, the limited mechanical and long-term stability of zwitterionic coatings, and nonuniform degradation and debris from biodegradable polymers.

For encapsulation, an Al2O3/HfO2 nanolaminate below 10 nm extended the lifetime of copper plasmonic nanodisks in PBS at 37 °C from about 5 h to about 180 days, about 1.8 times longer than single layers. Accelerated testing in PBS at 96 °C indicated that the barrier of thermally grown SiO2 would be maintained for about 70 years, and a liquid crystal polymer electrode array (water absorption below 0.04%) had a projected lifetime of 14 years. The review points out that inorganic barriers are not flexible enough for moving tissue, which motivates inorganic/organic hybrid layers.

Among adhesives, a polydopamine hydrogel with partially reduced graphene oxide reached 80 S/m and about 30 kPa on porcine skin, and an octopus-inspired conductive adhesive held 2.0 and 1.0 to 1.5 N/cm2 on dry and moist pig skin replicas for over 1000 cycles; the review notes that catechol chemistry can leave residues and hydrogen peroxide and that gecko-type adhesion is lost in liquid. Among self-healing materials, an EGaIn electrode encapsulated in a hydrogen-bonded elastomer stretched to 500% and recovered its mechanical and electrical properties after 12 h in artificial sweat, and a conductive hydrogel glove recovered its electrical signal within 10 s after healing, compared with 100 s for the elastomer system. Healing of the cited polymer semiconductor required chloroform immersion and annealing at 150 °C.

Open questions

The authors identify the burden of device implantation on patients, the restriction of current sensors to a single signal and the need for multiplexed sensing, and the lack of wireless and battery-free operation in laboratory bioelectronics as challenges for commercialization.

How it connects to other research

Anderson and colleagues reviewed the foreign body reaction as the response of macrophages and foreign-body giant cells to implanted materials and the surface properties that modulate it, whereas this review compiles material strategies, from antifouling coatings to encapsulation, adhesion and self-healing, that address that reaction together with mechanical mismatch and unstable device–tissue interfaces.