RESUMO
Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.
Assuntos
Implantes Absorvíveis , Encéfalo/metabolismo , Eletrônica/instrumentação , Monitorização Fisiológica/instrumentação , Próteses e Implantes , Silício , Implantes Absorvíveis/efeitos adversos , Administração Cutânea , Animais , Temperatura Corporal , Encéfalo/cirurgia , Desenho de Equipamento , Hidrólise , Masculino , Monitorização Fisiológica/efeitos adversos , Especificidade de Órgãos , Pressão , Próteses e Implantes/efeitos adversos , Ratos , Ratos Endogâmicos Lew , Telemetria/instrumentação , Tecnologia sem Fio/instrumentaçãoRESUMO
New options in the material context of transient electronics are essential to create or expand potential applications and to progress in the face of technological challenges. A soft, transparent, and cost-effective polymer of levan polysaccharide that is capable of complete, programmable dissolution is described when immersed in water and implanted in an animal model. The results include chemical analysis, the kinetics of hydrolysis, and adjustable dissolution rates of levan, and a simple theoretical model of reactive diffusion governed by temperature. In vivo experiments of the levan represent nontoxicity and biocompatibility without any adverse reactions. On-demand, selective control of dissolution behaviors with an animal model demonstrates an effective triggering strategy to program the system's lifetime, providing the possibility of potential applications in envisioned areas such as bioresorbable electronic implants and drug release systems.
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Eletrônica , Frutanos/química , Polissacarídeos/química , Animais , Magnésio/química , Metais/química , Óxidos/química , Ratos Sprague-Dawley , Semicondutores , Silício/química , Transistores EletrônicosRESUMO
Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required.
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Implantes Absorvíveis , Mapeamento Encefálico , Ondas Encefálicas/fisiologia , Córtex Cerebral/fisiologia , Eletrodos Implantados , Silício , Animais , Mapeamento Encefálico/instrumentação , Mapeamento Encefálico/métodos , Ratos , Silício/química , Silício/farmacologiaRESUMO
A paradigm shift for implantable medical devices lies at the confluence between regenerative medicine, where materials remodel and integrate in the biological milieu, and technology, through the use of recently developed material platforms based on biomaterials and bioresorbable technologies such as optics and electronics. The union of materials and technology in this context enables a class of biomedical devices that can be optically or electronically functional and yet harmlessly degrade once their use is complete. We present here a fully degradable, remotely controlled, implantable therapeutic device operating in vivo to counter a Staphylococcus aureus infection that disappears once its function is complete. This class of device provides fully resorbable packaging and electronics that can be turned on remotely, after implantation, to provide the necessary thermal therapy or trigger drug delivery. Such externally controllable, resorbable devices not only obviate the need for secondary surgeries and retrieval, but also have extended utility as therapeutic devices that can be left behind at a surgical or suturing site, following intervention, and can be externally controlled to allow for infection management by either thermal treatment or by remote triggering of drug release when there is retardation of antibiotic diffusion, deep infections are present, or when systemic antibiotic treatment alone is insufficient due to the emergence of antibiotic-resistant strains. After completion of function, the device is safely resorbed into the body, within a programmable period.
Assuntos
Anti-Infecciosos/administração & dosagem , Seda/química , Implantes Absorvíveis , Animais , Infecções Bacterianas/prevenção & controle , Biopolímeros/química , Sistemas de Liberação de Medicamentos , Eletrônica , Desenho de Equipamento , Equipamentos e Provisões , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ondas de Rádio , Infecções Estafilocócicas , Staphylococcus aureus , Temperatura , Termodinâmica , Tecnologia sem FioRESUMO
Transient electronics represents an emerging class of technology that exploits materials and/or device constructs that are capable of physically disappearing or disintegrating in a controlled manner at programmed rates or times. Inorganic semiconductor nanomaterials such as silicon nanomembranes/nanoribbons provide attractive choices for active elements in transistors, diodes and other essential components of overall systems that dissolve completely by hydrolysis in biofluids or groundwater. We describe here materials, mechanics, and design layouts to achieve this type of technology in stretchable configurations with biodegradable elastomers for substrate/encapsulation layers. Experimental and theoretical results illuminate the mechanical properties under large strain deformation. Circuit characterization of complementary metal-oxide-semiconductor inverters and individual transistors under various levels of applied loads validates the design strategies. Examples of biosensors demonstrate possibilities for stretchable, transient devices in biomedical applications.
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Técnicas Biossensoriais/métodos , Elastômeros/química , Nanotecnologia/métodos , Silício/química , Eletrônica , Nanoestruturas/química , SemicondutoresRESUMO
Quantitative phase imaging (QPI) utilizes the fact that the phase of an imaging field is much more sensitive than its amplitude. As fields from the source interact with the specimen, local variations in the phase front are produced, which provide structural information about the sample and can be used to reconstruct its topography with nanometer accuracy. QPI techniques do not require staining or coating of the specimen and are therefore nondestructive. Diffraction phase microscopy (DPM) combines many of the best attributes of current QPI methods; its compact configuration uses a common-path off-axis geometry which realizes the benefits of both low noise and single-shot imaging. This unique collection of features enables the DPM system to monitor, at the nanoscale, a wide variety of phenomena in their natural environments. Over the past decade, QPI techniques have become ubiquitous in biological studies and a recent effort has been made to extend QPI to materials science applications. We briefly review several recent studies which include real-time monitoring of wet etching, photochemical etching, surface wetting and evaporation, dissolution of biodegradable electronic materials, and the expansion and deformation of thin-films. We also discuss recent advances in semiconductor wafer defect detection using QPI.
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Aumento da Imagem/instrumentação , Teste de Materiais/instrumentação , Microscopia de Contraste de Fase/instrumentação , Imagem Molecular/instrumentação , Nanopartículas/ultraestrutura , Processamento de Sinais Assistido por Computador/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , LentesRESUMO
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.
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Técnicas Biossensoriais , Desenho de Equipamento , Bexiga Urinária , Humanos , Técnicas Biossensoriais/instrumentação , Próteses e Implantes , Coração , Dispositivos Eletrônicos Vestíveis , Animais , Eletrônica/instrumentaçãoRESUMO
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.
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Implantes Absorvíveis , Hérnia Abdominal , Humanos , Telas Cirúrgicas , Hérnia Abdominal/cirurgia , Sistemas de Liberação de Medicamentos , EletrônicaRESUMO
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.
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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 (â¼38 °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.
Assuntos
Técnicas Biossensoriais , Elastômeros , Elastômeros/química , Materiais Biocompatíveis/química , Implantes Absorvíveis , Polímeros/química , Poliésteres/químicaRESUMO
Chronic wounds affect ~2% of the U.S. population and increase risks of amputation and mortality. Unfortunately, treatments for such wounds are often expensive, complex, and only moderately effective. Electrotherapy represents a cost-effective treatment; however, its reliance on bulky equipment limits its clinical use. Here, we introduce water-powered, electronics-free dressings (WPEDs) that offer a unique solution to this issue. The WPED performs even under harsh conditions-situations wherein many present treatments fail. It uses a flexible, biocompatible magnesium-silver/silver chloride battery and a pair of stimulation electrodes; upon the addition of water, the battery creates a radial electric field. Experiments in diabetic mice confirm the WPED's ability to accelerate wound closure and promote healing by increasing epidermal thickness, modulating inflammation, and promoting angiogenesis. Across preclinical wound models, the WPED-treated group heals faster than the control with wound closure rates comparable to treatments requiring expensive biologics and/or complex electronics. The results demonstrate the WPED's potential as an effective and more practical wound treatment dressing.
Assuntos
Bandagens , Cicatrização , Animais , Camundongos , Água/química , Eletrônica , Diabetes Mellitus Experimental/terapia , Humanos , Modelos Animais de Doenças , Terapia por Estimulação Elétrica/métodosRESUMO
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.
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The combined use of ZnO, Mg, MgO, and silk provides routes to classes of thin-film transistors and mechanical energy harvesters that are soluble in water and biofluids. Experimental and theoretical studies of the operational aspects and dissolution properties of this type of transient electronics technology illustrate its various capabilities. Application opportunities range from resorbable biomedical implants, to environmentally dissolvable sensors, and degradable consumer electronics.
Assuntos
Materiais Biocompatíveis/química , Eletrônica/instrumentação , Fontes Geradoras de Energia , Óxido de Zinco/química , Eletricidade , Cinética , Solubilidade , Transistores Eletrônicos , Água/químicaRESUMO
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.
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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.
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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.
Assuntos
Robótica , Dispositivos Eletrônicos Vestíveis , Elastômeros/química , Eletrônica , Próteses e ImplantesRESUMO
Current standard clinical options for patients with detrusor underactivity (DUA) or underactive bladderâthe inability to release urine naturallyâinclude 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.
Assuntos
Bexiga Inativa , Bexiga Urinária , AnimaisRESUMO
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.
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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.
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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.