Biomedical Device Surface Treatment by Laser-Driven Hydroxyapatite Penetration-Synthesis Technique for Gapless PEEK-to-Bone Integration.

Polyetheretherketone (PEEK), a bioinert polymer known for its mechanical properties similar to bone, is capable of averting stress shielding. Due to these attributes, it finds applications in diverse fields like orthopedics, encompassing cervical disc replacement for the neck and spine, along with dentistry and plastic surgery. However, due to insufficient bonding with bone, various methods such as hydroxyapatite (HA) coating on the surface are attempted. Nonetheless, the interface between the polymer and ceramic, two different materials, tended to delaminate after transplantation, posing challenges in preventing implant escape or dislodgement. This research delves into the laser-driven hydroxyapatite penetration-synthesis technique. Differing from conventional coating methods that bond layers of dissimilar materials like HA and PEEK, this technology focuses on synthesizing and infiltrating ionized HA within the PEEK substrate resulting in an interface-free HA-PEEK surface. Conversely, HA-PEEK with this technology applied achieves complete, gap-free direct bone-implant integration.  Our research involved the analysis of various aspects. By means of these, we quantitatively assesed the enhanced bone bonding characteristics of HA-PEEK surfaces treated with this approach and offered and explanation for the mechanism responsible for direct bone integration.

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.

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.

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.

Photothermal Lithography for Realizing a Stretchable Multilayer Electronic Circuit Using a Laser.

Photolithography is a well-established fabrication method for realizing multilayer electronic circuits. However, it is challenging to adopt photolithography to fabricate intrinsically stretchable multilayer electronic circuits fully composed of an elastomeric matrix, due to the opacity of thick stretchable nanocomposite conductors. Here, we present photothermal lithography that can pattern elastomeric conductors and via holes using pulsed lasers. The photothermal-patterned stretchable nanocomposite conductor exhibits 3 times higher conductivity (5940 S cm-1) and 5 orders of magnitude lower resistance change (R/R0 = 40) under a 30% strained 5000th cyclic stretch, compared to those of a screen-printed conductor, based on the percolation network formed by spatial heating of the laser. In addition, a 50 µm sized stretchable via holes can be patterned on the passivation without material ablation and electrical degradation of the bottom conductor. By repeatedly patterning the conductor and via holes, highly conductive and durable multilayer circuits can be stacked with layer-by-layer material integration. Finally, a stretchable wireless pressure sensor and passive matrix LED array are demonstrated, thus showing the potential for a stretchable multilayer electronic circuit with durability, high density, and multifunctionality.

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.

Improving hydroxyapatite coating ability on biodegradable metal through laser-induced hydrothermal coating in liquid precursor: Application in orthopedic implants.

During the past decade, there has been extensive research toward the possibility of exploring magnesium and its alloys as biocompatible and biodegradable materials for implantable applications. Its practical medical application, however, has been limited to specific areas owing to rapid corrosion in the initial stage and the consequent complications. Surface coatings can significantly reduce the initial corrosion of Mg alloys, and several studies have been carried out to improve the adhesion strength of the coating to the surfaces of the alloys. The composition of hydroxyapatite (HAp) is very similar to that of bone tissue; it is one of the most commonly used coating materials for bone-related implants owing to favorable osseointegration post-implantation. In this study, HAp was coated on Mg using nanosecond laser coating, combining the advantages of chemical and physical treatments. Photothermal heat generated in the liquid precursor by the laser improved the adhesion of the coating through the precipitation and growth of HAp at the localized nanosecond laser focal area and increased the corrosion resistance and cell adhesion of Mg. The physical, crystallographic, and chemical bondings were analyzed to explore the mechanism through which the surface adhesion between Mg and the HAp coating layer increased. The applicability of the coating to Mg screws used for clinical devices and improvement in its corrosion property were confirmed. The liquid environment-based laser surface coating technique offers a simple and quick process that does not require any chemical ligands, and therefore, overcomes a potential obstacle in its clinical use.

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.

Hetero-Integration of Silicon Nanomembranes with 2D Materials for Bioresorbable, Wireless Neurochemical System.

Although neurotransmitters are key substances closely related to evaluating degenerative brain diseases as well as regulating essential functions in the body, many research efforts have not been focused on direct observation of such biochemical messengers, rather on monitoring relatively associated physical, mechanical, and electrophysiological parameters. Here, a bioresorbable silicon-based neurochemical analyzer incorporated with 2D transition metal dichalcogenides is introduced as a completely implantable brain-integrated system that can wirelessly monitor time-dynamic behaviors of dopamine and relevant parameters in a simultaneous mode. An extensive range of examinations of molybdenum/tungsten disulfide (MoS2 /WS2 ) nanosheets and catalytic iron nanoparticles (Fe NPs) highlights the underlying mechanisms of strong chemical and target-specific responses to the neurotransmitters, along with theoretical modeling tools. Systematic characterizations demonstrate reversible, stable, and long-term operational performances of the degradable bioelectronics with excellent sensitivity and selectivity over those of non-dissolvable counterparts. A complete set of in vivo experiments with comparative analysis using carbon-fiber electrodes illustrates the capability for potential use as a clinically accessible tool to associated neurodegenerative diseases.

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.

Expandable and implantable bioelectronic complex for analyzing and regulating real-time activity of the urinary bladder.

Underactive bladder or detrusor underactivity (DUA), that is, not being able to micturate, has received less attention with little research and remains unknown or limited on pathological causes and treatments as opposed to overactive bladder, although the syndrome may pose a risk of urinary infections or life-threatening kidney damage. Here, we present an integrated expandable electronic and optoelectronic complex that behaves as a single body with the elastic, time-dynamic urinary bladder with substantial volume changes up to ~300%. The system configuration of the electronics validated by the theoretical model allows conformal, seamless integration onto the urinary bladder without a glue or suture, enabling precise monitoring with various electrical components for real-time status and efficient optogenetic manipulation for urination at the desired time. In vivo experiments using diabetic DUA models demonstrate the possibility for practical uses of high-fidelity electronics in clinical trials associated with the bladder and other elastic organs.

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.

Intra-mitochondrial self-assembly to overcome the intracellular enzymatic degradation of l-peptides.

The design of peptide-based therapeutics is generally based on the replacement of l-amino acids with d-isomers to obtain improved therapeutic efficiency. However, d-isomers are expensive and frequently induce undesirable immune responses. In the present work, we demonstrate that an intra-mitochondrially self-assembling amphiphilic peptide exhibits analogous activity in both d- and l-isomeric forms. This outcome is in contrast to the general observation considering higher therapeutic efficiencies of d-isomers compared with l-analogues. This suggests that l-peptides overcome proteolytic degradation during intra-mitochondrial self-assembly both in vitro and in vivo.

3D Printed, Customizable, and Multifunctional Smart Electronic Eyeglasses for Wearable Healthcare Systems and Human-Machine Interfaces.

Personal accessories such as glasses and watches that we usually carry in our daily life can yield useful information from the human body, yet most of them are limited to exercise-related parameters or simple heart rates. Since these restricted characteristics might arise from interfaces between the body and items as one of the main reasons, an interface design considering such a factor can provide us with biologically meaningful data. Here, we describe three-dimensional-printed, personalized, multifunctional electronic eyeglasses (E-glasses), not only to monitor various biological phenomena but also to propose a strategy to coordinate the recorded data for active commands and game operations for human-machine interaction (HMI) applications. Soft, highly conductive composite electrodes embedded in the E-glasses enable us to achieve reliable, continuous recordings of physiological activities. UV-responsive, color-tunable lenses using an electrochromic ionic gel offer the functionality of both eyeglass and sunglass modes, and accelerometers provide the capability of tracking precise human postures and behaviors. Detailed studies of electrophysiological signals including electroencephalogram and electrooculogram demonstrate the feasibility of smart electronic glasses for practical use as a platform for future HMI systems.

Heterochiral Assembly of Amphiphilic Peptides Inside the Mitochondria for Supramolecular Cancer Therapeutics.

Self-assembly of peptides containing both l- and d-isomers often results in nanostructures with enhanced properties compared to their enantiomeric analogues, such as faster kinetics of formation, higher mechanical strength, and enzymatic stability. However, occurrence and consequences of the heterochiral assembly in the cellular microenvironment are unknown. In this study, we monitored heterochiral assembly of amphiphilic peptides inside the cell, specifically mitochondria of cancer cells, resulting in nanostructures with refined morphological and biological properties owing to the superior interaction between the backbones of opposite chirality. We have designed a mitochondria penetrating tripeptide containing a diphenyl alanine building unit, named as Mito-FF due to their mitochondria targeting ability. The short peptide amphiphile, Mito-FF co-assembled with its mirror pair, Mito-ff, induced superfibrils of around 100 nm in diameter and 0.5-1 µm in length, while enantiomers formed only narrow fibers of 10 nm in diameter. The co-administration of Mito-FF and Mito-ff in the cell induced drastic mitochondrial disruption both in vitro and in vivo. The experimental and theoretical analyses revealed that pyrene capping played a major role in inducing superfibril morphology upon the co-assembly of racemic peptides. This work shows the impact of chirality control over the peptide self-assembly inside the biological system, thus showing a potent strategy for fabricating promising peptide biomaterials by considering chirality as a design modality.