Recent advances in soft, implantable electronics for dynamic organs.

Unlike conventional rigid counterparts, soft and stretchable electronics forms crack- or defect-free conformal interfaces with biological tissues, enabling precise and reliable interventions in diagnosis and treatment of human diseases. Intrinsically soft and elastic materials, and device designs of innovative configurations and structures leads to the emergence of such features, particularly, the mechanical compliance provides seamless integration into continuous movements and deformations of dynamic organs such as the bladder and heart, without disrupting natural physiological functions. This review introduces the development of soft, implantable electronics tailored for dynamic organs, covering various materials, mechanical design strategies, and representative applications for the bladder and heart, and concludes with insights into future directions toward clinically relevant tools.

Soft, Long-Lived, Bioresorbable Electronic Surgical Mesh with Wireless Pressure Monitor and On-Demand Drug Delivery.

Current research in the area of surgical mesh implants is somewhat limited to traditional designs and synthesis of various mesh materials, whereas meshes with multiple functions may be an effective approach to address long-standing challenges including postoperative complications. Herein, a bioresorbable electronic surgical mesh is presented that offers high mechanical strength over extended timeframes, wireless post-operative pressure monitoring, and on-demand drug delivery for the restoration of tissue structure and function. The study of materials and mesh layouts provides a wide range of tunability of mechanical and biochemical properties. Dissolvable dielectric composite with porous structure in a pyramidal shape enhances sensitivity of a wireless capacitive pressure sensor, and resistive microheaters integrated with inductive coils provide thermo-responsive drug delivery system for an antibacterial agent. In vivo evaluations demonstrate reliable, long-lived operation, and effective treatment for abdominal hernia defects, by clear evidence of suppressed complications such as adhesion formation and infections.

Synthesis of shape-programmable elastomer for a bioresorbable, wireless nerve stimulator.

Materials that have the ability to manipulate shapes in response to stimuli such as heat, light, humidity and magnetism offer a means for versatile, sophisticated functions in soft robotics or biomedical implants, while such a reactive transformation has certain drawbacks including high operating temperatures, inherent rigidity and biological hazard. Herein, we introduce biodegradable, self-adhesive, shape-transformable poly (L-lactide-co-ε-caprolactone) (BSS-PLCL) that can be triggered via thermal stimulation near physiological temperature (∼38 °C). Chemical inspections confirm the fundamental properties of the synthetic materials in diverse aspects, and study on mechanical and biochemical characteristics validates exceptional stretchability up to 800 % and tunable dissolution behaviors under biological conditions. The integration of the functional polymer with a bioresorbable electronic system highlights potential for a wide range of biomedical applications.

Highly Elastic, Bioresorbable Polymeric Materials for Stretchable, Transient Electronic Systems.

Substrates or encapsulants in soft and stretchable formats are key components for transient, bioresorbable electronic systems; however, elastomeric polymers with desired mechanical and biochemical properties are very limited compared to non-transient counterparts. Here, we introduce a bioresorbable elastomer, poly(glycolide-co-ε-caprolactone) (PGCL), that contains excellent material properties including high elongation-at-break (< 1300%), resilience and toughness, and tunable dissolution behaviors. Exploitation of PGCLs as polymer matrices, in combination with conducing polymers, yields stretchable, conductive composites for degradable interconnects, sensors, and actuators, which can reliably function under external strains. Integration of device components with wireless modules demonstrates elastic, transient electronic suture system with on-demand drug delivery for rapid recovery of post-surgical wounds in soft, time-dynamic tissues.

Structure of solid-supported lipid membrane probed by noble metal nanoparticle deposition.

Direct deposition of a noble metal layer onto a solid-supported membrane was proposed as an indirect microscopy tool to visually observe different lipid phases that may develop in the lipid membrane. The method relied on the different permeability of the lipid membrane towards the incident atoms during deposition. Liquid state or structural defects such as phase boundaries, step ledges in a multi-lamellar stack, and pores permitted the metal atoms to penetrate and nucleate inside the membrane whereas rigid gel state was relatively impermeable to the incident atoms, thus enabling visualization of liquid phase or structural defects inside the gel state. Based on the proposed method, we demonstrated the phase states resulting from thermotropic transitions of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), dioleoylphosphatidylethanolamine (DOPE)/DPPC mixture, and 1,2-dioleoyl-3-trimethylammonium propane (DOTAP). Although the proposed method does not allow in-situ observation of equilibrium states, the method should be an excellent complementary tool for visualizing the lipid phases as the method can resolve fine structural details (up to tens of nanometer scale) as seen in the DPPC membrane while providing macroscopic images (up to several micrometers).

Deposition of metal nanoparticles on phospholipid multilayer membranes modified by gramicidin.

A planar dipalmitoyl phosphatidylcholine (DPPC) multilayer phospholipid membrane was structurally modified by introducing a transmembrane protein, gramicidin (up to 25 mol %), to study its effect on the metal nanoparticles deposited on the membrane. Without gramicidin, when 3-nm-thick Ag, Sn, Al, and Au were deposited, the nanoparticles hardly nucleated on the DPPC membrane in rigid gel state (except for Au); however, the gramicidin addition dramatically enhanced the DPPC membrane surface's affinity for metal atoms so that a dense array of metal (Ag, Sn, and Au) or metal-oxide (Al-oxide) nanoparticles was produced on the membrane surface. The particle sizes ranged from 3 to 15 nm depending on the metal and gramicidin concentration, whereas the particle density was strongly dictated by the gramicidin concentration. The proposed method provides a convenient, generally applicable synthesis route for preparing different metal or metal-oxide nanoparticles on a relatively robust biocompatible membrane.

Coalescence and polygonization of Au nanoparticles embedded in liquid-crystalline lipid membrane.

Coarsening behavior of Au nanoparticles (AuNPs) embedded in a liquid crystalline lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) membrane was investigated by heat treating the AuNP-embedded DOTAP membrane at 80 degrees C with 15% and 80% relative humidity (RH). The coarsening rate was (D) to approximately t0.6 regardless of the humidity; however, the spatial distribution and the coarsening mechanism differed depending on the humidity. In addition, extended treatment at 15% RH resulted in formation of large polygonized AuNPs from the lipid segregation.

Micropatterned Elastomeric Composites for Encapsulation of Transient Electronics.

Although biodegradable, transient electronic devices must dissolve or decompose via environmental factors, an effective waterproofing or encapsulation system is essential for reliable, durable operation for a desired period of time. Existing protection approaches use multiple or alternate layers of electrically inactive organic/inorganic elements combined with polymers; however, their high mechanical stiffness is not suitable for soft, time-dynamic biological tissues/skins/organs. Here, we introduce a stretchable, bioresorbable encapsulant using nanoparticle-incorporated elastomeric composites with modifications of surface morphology. Nature-inspired micropatterns reduce the diffusion area for water molecules, and embedded nanoparticles impede water permeation, which synergistically enhances the water-barrier performance. Empirical and theoretical evaluations validate the encapsulation mechanisms under strains. Demonstration of a soft, degradable shield with an optical component under a biological solution highlights the potential applicability of the proposed encapsulation strategy.

Ultra-stretchable and biodegradable elastomers for soft, transient electronics.

As rubber-like elastomers have led to scientific breakthroughs in soft, stretchable characteristics-based wearable, implantable electronic devices or relevant research fields, developments of degradable elastomers with comparable mechanical properties could bring similar technological innovations in transient, bioresorbable electronics or expansion into unexplored areas. Here, we introduce ultra-stretchable, biodegradable elastomers capable of stretching up to ~1600% with outstanding properties in toughness, tear-tolerance, and storage stability, all of which are validated by comprehensive mechanical and biochemical studies. The facile formation of thin films enables the integration of almost any type of electronic device with tunable, suitable adhesive strengths. Conductive elastomers tolerant/sensitive to mechanical deformations highlight possibilities for versatile monitoring/sensing components, particularly the strain-tolerant composites retain high levels of conductivities even under tensile strains of ~550%. Demonstrations of soft electronic grippers and transient, suture-free cardiac jackets could be the cornerstone for sophisticated, multifunctional biodegradable electronics in the fields of soft robots and biomedical implants.

Wireless, Fully Implantable and Expandable Electronic System for Bidirectional Electrical Neuromodulation of the Urinary Bladder.

Current standard clinical options for patients with detrusor underactivity (DUA) or underactive bladder─the inability to release urine naturally─include the use of medications, voiding techniques, and intermittent catheterization, for which the patient inserts a tube directly into the urethra to eliminate urine. Although those are life-saving techniques, there are still unfavorable side effects, including urinary tract infection (UTI), urethritis, irritation, and discomfort. Here, we report a wireless, fully implantable, and expandable electronic complex that enables elaborate management of abnormal bladder function via seamless integrations with the urinary bladder. Such electronics can not only record multiple physiological parameters simultaneously but also provide direct electrical stimulation based on a feedback control system. Uniform distribution of multiple stimulation electrodes via mesh-type geometry realizes low-impedance characteristics, which improves voiding/urination efficiency at the desired times. In vivo evaluations using live, free-moving animal models demonstrate system-level functionality.

Zebra-inspired stretchable, biodegradable radiation modulator for all-day sustainable energy harvesters.

Recent advances in passive radiative cooling systems describe a variety of strategies to enhance cooling efficiency, while the integration of such technology with a bioinspired design using biodegradable materials can offer a research opportunity to generate energy in a sustainable manner, favorable for the temperature/climate system of the planet. Here, we introduce stretchable and ecoresorbable radiative cooling/heating systems engineered with zebra stripe-like patterns that enable the generation of a large in-plane temperature gradient for thermoelectric generation. A comprehensive study of materials with theoretical evaluations validates the ability to accomplish the target performances even under external mechanical strains, while all systems eventually disappear under physiological conditions. Use of the zebra print for selective radiative heating demonstrates an unexpected level of temperature difference compared to use of radiative cooling emitters alone, which enables producing energy through resorbable silicon-based thermoelectric devices. The overall result suggests the potential of scalable, ecofriendly renewable energy systems.

Effect of temperature and humidity on coarsening behavior of Au nanoparticles embedded in liquid crystalline lipid membrane.

Coarsening behavior of the Au nanoparticles produced by thermal evaporation of Au onto a liquid crystalline lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) membrane was investigated by subjecting the nanoparticle-embedded DOTAP membrane to two different annealing conditions (at 100 °C under no humidity and at 20 °C and 80% relative humidity). Although the coarsening rate was relatively slow because of the low temperature (from 5.6 nm in the as-deposited state to ~7 nm after 30 h), it was identified that at 100 °C without humidity the Au nanoparticles resulted in shape refinement whereas the high humidity at 20 °C induced self-organization of the nanoparticles into a monolayer. It was also found that annealing in both cases tended to segregate the lipid molecules from the nanoparticle array and forced the nanoparticles into a tighter area. In the case of the high-humidity sample, the lipid segregation eventually led to extensive coalescence of the Au nanoparticles.

Tunable and scalable fabrication of block copolymer-based 3D polymorphic artificial cell membrane array.

Owing to their excellent durability, tunable physical properties, and biofunctionality, block copolymer-based membranes provide a platform for various biotechnological applications. However, conventional approaches for fabricating block copolymer membranes produce only planar or suspended polymersome structures, which limits their utilization. This study is the first to demonstrate that an electric-field-assisted self-assembly technique can allow controllable and scalable fabrication of 3-dimensional block copolymer artificial cell membranes (3DBCPMs) immobilized on predefined locations. Topographically and chemically structured microwell array templates facilitate uniform patterning of block copolymers and serve as reactors for the effective growth of 3DBCPMs. Modulating the concentration of the block copolymer and the amplitude/frequency of the electric field generates 3DBCPMs with diverse shapes, controlled sizes, and high stability (100% survival over 50 days). In vitro protein-membrane assays and mimicking of human intestinal organs highlight the potential of 3DBCPMs for a variety of biological applications such as artificial cells, cell-mimetic biosensors, and bioreactors.

Biologically Safe, Degradable Self-Destruction System for On-Demand, Programmable Transient Electronics.

The lifetime of transient electronic components can be programmed via the use of encapsulation/passivation layers or of on-demand, stimuli-responsive polymers (heat, light, or chemicals), but yet most research is limited to slow dissolution rate, hazardous constituents, or byproducts, or complicated synthesis of reactants. Here we present a physicochemical destruction system with dissolvable, nontoxic materials as an efficient, multipurpose platform, where chemically produced bubbles rapidly collapse device structures and acidic molecules accelerate dissolution of functional traces. Extensive studies of composites based on biodegradable polymers (gelatin and poly(lactic-co-glycolic acid)) and harmless blowing agents (organic acid and bicarbonate salt) validate the capability for the desired system. Integration with wearable/recyclable electronic components, fast-degradable device layouts, and wireless microfluidic devices highlights potential applicability toward versatile/multifunctional transient systems. In vivo toxicity tests demonstrate biological safety of the proposed system.

Advanced Materials and Systems for Biodegradable, Transient Electronics.

Transient electronics refers to an emerging class of advanced technology, defined by an ability to chemically or physically dissolve, disintegrate, and degrade in actively or passively controlled fashions to leave environmentally and physiologically harmless by-products in environments, particularly in bio-fluids or aqueous solutions. The unusual properties that are opposite to operational modes in conventional electronics for a nearly infinite time frame offer unprecedented opportunities in research areas of eco-friendly electronics, temporary biomedical implants, data-secure hardware systems, and others. This review highlights the developments of transient electronics, including materials, manufacturing strategies, electronic components, and transient kinetics, along with various potential applications.

Enhancement of membrane protein reconstitution on 3D free-standing lipid bilayer array in a microfluidic channel.

The bio-sensory organs of living creatures have evolved to have the best sensing performance. They have 3-dimensional protrusions that have large surface areas to accommodate a large number of membrane proteins such as ion channels and G-protein coupled receptors, resulting in high sensitivity and specificity to target molecules. From the perspective of mimicking this system, BLM, which has been used extensively as a platform for a single nanopore-based sensing systems, has some limitations, i.e., some residual solvent, low mechanical stability, small surface area for appropriate stability, and difficulty in high-throughput fabrication. Herein, to eliminate these limitations, a solvent-free, size-controllable, 3-dimensional free-standing lipid bilayer (3DFLB) structure array with high stability (∼130 h) and high density (∼300,000 cm-2) is proposed, and its structural advantages for efficient and rapid protein reconstitution, compared to BLM, is demonstrated by human 5-HT3A receptor assay as well as α-hemolysin assay. A continuous process of 3DFLB array fabrication, 5-HT3A reconstitution, and 5-HT detections in a microfluidic channel proves the applicability of the proposed structures as a highly-sensitive sensing platform mimicking bio-sensory organs.

Tightly Sealed 3D Lipid Structure Monolithically Generated on Transparent SU-8 Microwell Arrays for Biosensor Applications.

Artificial lipid membranes are excellent candidates for new biosensing platforms because their structures are similar to cell membranes and it is relatively easy to modify the composition of the membrane. The freestanding structure is preferable for this purpose because of the more manageable reconstitution of the membrane protein. Therefore, most of the lipid membranes for biosensing are based on two-dimensional structures that are fixed on a solid substrate (unlike floating liposomes) even though they have some disadvantages, such as low stability, small surface area, and potential retention of solvent in the membrane. In this paper, three-dimensional freestanding lipid bilayer (3D FLB) arrays were fabricated uniformly on SU-8 microwells without any toxic solvent. The 3D FLBs have better stability and larger surface area due to their cell-like structure. In order to improve the sealing characteristics of the 3D FLBs, the applied frequency of the ac field was controlled during the electroformation. The 3D FLBs were observed through transparent SU-8 microwell arrays using confocal microscopy and demonstrated perfect sealing until 5.5 days after the electroformation at more than 1 kHz. Also, the details of the sealing of a fixed 3D freestanding lipid structure were discussed for the first time. The unilamellarity and biofunctionality of the 3D FLBs were verified by a transport protein (α-hemolysin) assay.

Stabilization of solid-supported phospholipid multilayer against water by gramicidin addition.

It was demonstrated that hydrophobicity of solid supported planar dipalmitoyl phosphatidylcholine (DPPC) phospholipid multilayer can be greatly increased by incorporating a transmembrane protein, gramicidin, into the DPPC membrane. The contact angle of deionized water droplet on the gramicidin-modified DPPC membrane increased from 0° (complete wetting) without gramicidin to 55° after adding 15 mol % gramicidin. The increased hydrophobicity of the gramicidin-modified DPPC membrane allowed the membrane to remain stable at the air/water interface as well as underwater. The Au nanoparticles deposited on the gramicidin-modified DPPC membrane reproduced the characteristic surface plasmon resonance peak after being kept underwater or in phosphate-buffered saline solution for 5 days, attesting to the membrane stability in an aqueous environment. The enhanced underwater stability of the lipid multilayer substantially broadens the potential application of the lipid multilayer which includes biosensing, enzymatic fuel cell, surface enhanced Raman spectroscopy substrate.

Molecular dynamics simulation of interlayer water embedded in phospholipid bilayer.

1,2-dioleoyl-sn-glycero-3-phosphocholine lipid bilayer with a thin layer of water molecules inserted in the hydrophobic region was simulated at 300K to observe the pore structure formation during escape of the water molecules from the hydrophobic region. The transformation of the water slab into a cylindrical droplet in the hydrophobic region, which locally deformed the lipid monolayer, was prerequisite to the pore formation. If the thickness of the interlayer water was increased beyond a critical value, the local deformation was suppressed as such deformation would rupture the lipid bilayer. Hence, it was demonstrated that the pore structure formation or local permeability of the lipid membrane is closely related to the rigidity of the lipid membrane.