RESUMO
To construct tissue-like prosthetic materials, soft electroactive hydrogels are the best candidate owing to their physiological mechanical modulus, low electrical resistance and bidirectional stimulating and recording capability of electrophysiological signals from biological tissues1,2. Nevertheless, until now, bioelectronic devices for such prostheses have been patch type, which cannot be applied onto rough, narrow or deep tissue surfaces3-5. Here we present an injectable tissue prosthesis with instantaneous bidirectional electrical conduction in the neuromuscular system. The soft and injectable prosthesis is composed of a biocompatible hydrogel with unique phenylborate-mediated multiple crosslinking, such as irreversible yet freely rearrangeable biphenyl bonds and reversible coordinate bonds with conductive gold nanoparticles formed in situ by cross-coupling. Closed-loop robot-assisted rehabilitation by injecting this prosthetic material is successfully demonstrated in the early stage of severe muscle injury in rats, and accelerated tissue repair is achieved in the later stage.
Assuntos
Materiais Biocompatíveis , Hidrogéis , Próteses e Implantes , Ferimentos e Lesões , Animais , Ratos , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Condutividade Elétrica , Ouro/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Hidrogéis/uso terapêutico , Nanopartículas Metálicas/química , Músculos/lesões , Músculos/inervação , Robótica , Ferimentos e Lesões/reabilitação , Ferimentos e Lesões/cirurgiaRESUMO
Material advances in soft bioelectronics, particularly those based on stretchable nanocompositesâfunctional nanomaterials embedded in viscoelastic polymers with irreversible or reversible bondsâhave driven significant progress in translational medical device research. The unique mechanical properties inherent in the stretchable nanocomposites enable stiffness matching between tissue and device, as well as its spontaneous mechanical adaptation to in vivo environments, minimizing undesired mechanical stress and inflammation responses. Furthermore, these properties allow percolative networks of conducting fillers in the nanocomposites to be sustained even under repetitive tensile/compressive stresses, leading to stable tissue-device interfacing. Here, we present an in-depth review of materials strategies, fabrication/integration techniques, device designs, applications, and translational opportunities of nanocomposite-based soft bioelectronics, which feature intrinsic stretchability, self-healability, tissue adhesion, and/or syringe injectability. Among many, applications to brain, heart, and peripheral nerves are predominantly discussed, and translational studies in certain domains such as neuromuscular and cardiovascular engineering are particularly highlighted.
Assuntos
Nanocompostos , Nanocompostos/química , Humanos , Próteses e Implantes , Materiais Biocompatíveis/química , Animais , Polímeros/química , EletrônicaRESUMO
This study evaluated the prophylactic effect of localized biomimetic minocycline and systemic amoxicillin on immediate implant placement at infected extraction sites. Twelve mongrels with six implants each were randomly assigned to five groups: uninfected negative control (Group N); infected with oral complex bacteria (Group P); infected and treated with amoxicillin one hour before implant placement (Group A); infected and treated with minocycline during implant placement (Group B); and infected and treated with amoxicillin one hour before implant placement and with minocycline during implant placement (Group C). Radiographic bone level, gingival index (GI), probing depth (PD), papillary bleeding index (PBI), and removal torque (RT) were recorded. There was no significant difference between Groups A, B, and C for bone loss. Group A showed the highest RT, the lowest PBI, and significantly lower GI and PD values than Group P. Group B exhibited significantly higher RT value than Group N and significantly smaller PD value than Group P at 6 w postoperatively. Localized minocycline could improve implant success by reducing bone loss and increasing RT and systemic amoxicillin could maintain the stability of the peri-implant soft tissue. However, combined use of these two antibiotics did not augment the prophylactic effect.
RESUMO
Strain-tolerant reversible adhesion under harsh mechanical deformation is important for realizing long-lasting polymeric adhesives. Despite recent advances, cohesive failure within adhesives remains a critical problem that must be solved to achieve adhesion that is robust against humidity, heat, and mechanical stress. Here, we report a molecular rationale for designing an instantaneous polymeric adhesive with high strain tolerance (termed as iPASTE) even in a stretchable human-machine interface. The iPASTE consists of two biocompatible and eco-friendly polymers, linearly oligomerized green tea extracts, and poly(ethylene glycol) for densely assembled networks via dynamic and reversible hydrogen bonds. Other than the typical approach containing nanoclay or branched adhesive precursors, the linear configuration and conformation of such polymer chains within iPASTE lead to strong and moisture-resistant cohesion/adhesion. Based on the strain-tolerant adhesion of iPASTE, it was demonstrated that a subaqueous interactive human-machine interface integrated with a robot arm and a gold nanomembrane strain-sensitive electronic skin can precisely capture a slithery artificial fish by using finger gesture recognition.
Assuntos
Adesivos , Polímeros , Animais , Humanos , Adesivos/química , Polímeros/química , Hidrogéis/química , Estresse Mecânico , UmidadeRESUMO
The application of soft hydrogels to stretchable devices has attracted increasing attention in deformable bioelectronics owing to their unique characteristic, "modulus matching between materials and organs". Despite considerable progress, their low toughness, low conductivity, and absence of tissue adhesiveness remain substantial challenges associated with unstable skin-interfacing, where body movements undesirably disturb electrical signal acquisitions. Herein, we report a material design of a highly tough strain-dissipative and skin-adhesive conducting hydrogel fabricated through a facile one-step sol-gel transition and its application to an interactive human-machine interface. The hydrogel comprises a triple polymeric network where irreversible amide linkage of polyacrylamide with alginate and dynamic covalent bonds entailing conjugated polymer chains of poly(3,4-ethylenedioxythiophene)-co-(3-thienylboronic acid) are simultaneously capable of high stretchability (1300% strain), efficient strain dissipation (36,209 J/m2), low electrical resistance (590 Ω), and even robust skin adhesiveness (35.0 ± 5.6 kPa). Based on such decent characteristics, the hydrogel was utilized as a multifunctional layer for successfully performing either electrophysiological cardiac/muscular on-skin sensors or an interactive stretchable human-machine interface.
Assuntos
Hidrogéis , Polímeros , Humanos , Adesividade , Hidrogéis/química , Polímeros/química , Adesivos/química , Movimento , Condutividade ElétricaRESUMO
Recent studies on soft adhesives have sought to deeply understand how their chemical or mechanical structures interact strongly with living tissues. The aim is to optimally address the unmet needs of patients with acute or chronic diseases. Synergistic adhesion involving both electrostatic (hydrogen bonds) and mechanical interactions (capillarity-assisted suction stress) seems to be effective in overcoming the challenges associated with long-term unstable coupling to tissues. Here, an electrostatically and mechanically synergistic mechanism of residue-free, sustainable, in situ tissue adhesion by implementing hybrid multiscale architectonics. To deduce the mechanism, a thermodynamic model based on a tailored multiscale combinatory adhesive is proposed. The model supports the experimental results that the thermodynamically controlled swelling of the nanoporous hydrogel embedded in the hierarchical elastomeric structure enhances biofluid-insensitive, sustainable, in situ adhesion to diverse soft, slippery, and wet organ surfaces, as well as clean detachment in the peeling direction. Based on the robust tissue adhesion capability, universal reliable measurements of electrophysiological signals generated by various tissues, ranging from rodent sciatic nerve, the muscle, brain, and human skin, are successfully demonstrated.
Assuntos
Hidrogéis , Adesivos Teciduais , Adesivos/química , Humanos , Hidrogéis/química , Eletricidade Estática , Aderências Teciduais , Adesivos Teciduais/químicaRESUMO
For rapid and effective hemostasis of uncontrollable bleeding, versatile hemostatic agents have been emerging. Among them, polyphenol-derived adhesives have attracted those hemostatic materials due to instantaneous formation of sticky barriers by robust interactions between the material and the serum proteins from wound. However, a critical challenge in such phenolic materials lies in long-term storage due to spontaneous oxidation under humid environments, leading to changes in hemostatic capability and adhesive strength. Here, we report a transparent hemostatic film consisting of gallol-conjugated chitosan (CHI-G) for minimizing the phenolic oxidation even for 3 months and maintaining strong tissue adhesiveness and its hemostatic ability. The film undergoes a phase transition from solid to injectable hydrogels at physiological pH for efficiently stopping internal and external hemorrhage. Interestingly, the hemostatic capability of the CHI-G hydrogels after 3 month storage depends on (i) the folded microstructure of the polymer with optimal gallol modification and (ii) an initial phase of either a solution state or a solid film. When the hydrogels are originated from the dehydrated film, their successful hemostasis is observed in a liver bleeding model. Our finding would provide an insight for design rationale of hemostatic formulations with long shelf-life.
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Quitosana , Hemostáticos , Adesivos Teciduais , Adesivos/química , Quitosana/química , Hemorragia/tratamento farmacológico , Hemostasia , Hemostáticos/química , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Polifenóis/farmacologia , Adesivos Teciduais/químicaRESUMO
High-performance photodetecting materials with intrinsic stretchability and colour sensitivity are key requirements for the development of shape-tunable phototransistor arrays. Another challenge is the proper compensation of optical aberrations and noises generated by mechanical deformation and fatigue accumulation in a shape-tunable phototransistor array. Here we report rational material design and device fabrication strategies for an intrinsically stretchable, multispectral and multiplexed 5 × 5 × 3 phototransistor array. Specifically, a unique spatial distribution of size-tuned quantum dots, blended in a semiconducting polymer within an elastomeric matrix, was formed owing to surface energy mismatch, leading to highly efficient charge transfer. Such intrinsically stretchable quantum-dot-based semiconducting nanocomposites enable the shape-tunable and colour-sensitive capabilities of the phototransistor array. We use a deep neural network algorithm for compensating optical aberrations and noises, which aids the precise detection of specific colour patterns (for example, red, green and blue patterns) both under its flat state and hemispherically curved state (radius of curvature of 18.4 mm).
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Nanocompostos , Pontos Quânticos , Cor , PolímerosRESUMO
Soft neuroprosthetics that monitor signals from sensory neurons and deliver motor information can potentially replace damaged nerves. However, achieving long-term stability of devices interfacing peripheral nerves is challenging, since dynamic mechanical deformations in peripheral nerves cause material degradation in devices. Here, a durable and fatigue-resistant soft neuroprosthetic device is reported for bidirectional signaling on peripheral nerves. The neuroprosthetic device is made of a nanocomposite of gold nanoshell (AuNS)-coated silver (Ag) flakes dispersed in a tough, stretchable, and self-healing polymer (SHP). The dynamic self-healing property of the nanocomposite allows the percolation network of AuNS-coated flakes to rebuild after degradation. Therefore, its degraded electrical and mechanical performance by repetitive, irregular, and intense deformations at the device-nerve interface can be spontaneously self-recovered. When the device is implanted on a rat sciatic nerve, stable bidirectional signaling is obtained for over 5 weeks. Neural signals collected from a live walking rat using these neuroprosthetics are analyzed by a deep neural network to predict the joint position precisely. This result demonstrates that durable soft neuroprosthetics can facilitate collection and analysis of large-sized in vivo data for solving challenges in neurological disorders.
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Nervo Isquiático , Animais , Eletrodos Implantados , Nanocompostos , Polímeros , RatosRESUMO
Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.
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Eletrônica Médica/instrumentação , Eletrônica Médica/métodos , Neurocirurgia/instrumentação , Neurocirurgia/métodos , Nervos Periféricos/fisiologia , Animais , Engenharia Biomédica/instrumentação , Engenharia Biomédica/métodos , Sistema Nervoso Central/fisiologia , Sistema Nervoso Central/cirurgia , Ouro , Humanos , Masculino , Teste de Materiais , Modelos Animais , Tecido Nervoso/patologia , Tecido Nervoso/cirurgia , Nervos Periféricos/patologia , Nervos Periféricos/cirurgia , Polímeros/química , Próteses e Implantes , Ratos , Nervo Isquiático , Dispositivos Eletrônicos VestíveisRESUMO
Skin-inspired wearable electronic/biomedical systems based on functional nanomaterials with exceptional electrical and mechanical properties have revolutionized wearable applications, such as portable Internet of Things, personalized healthcare monitors, human-machine interfaces, and even always-connected precise medicine systems. Despite these advancements, including the ability to predict and to control nanolevel phenomena of functional nanomaterials precisely and strategies for integrating nanomaterials onto desired substrates without performance losses, skin-inspired electronic nanosystems are not yet feasible beyond proof-of-concept devices. In this Perspective, we provide an outlook on skin-like electronics through the review of several recent reports on various materials strategies and integration methodologies of stretchable conducting and semiconducting nanomaterials, which are used as electrodes and active layers in stretchable sensors, transistors, multiplexed arrays, and integrated circuits. To overcome the challenge of realizing robust electronic nanosystems, we discuss using nanomaterials in dynamically cross-linked polymer matrices, focusing on the latest innovations in stretchable self-healing electronics, which could change the paradigm of wearable electronics.
Assuntos
Materiais Biocompatíveis/química , Nanoestruturas/química , Polímeros/química , Pele , Dispositivos Eletrônicos Vestíveis , Técnicas Biossensoriais/instrumentação , Condutividade Elétrica , Eletrodos , Humanos , Semicondutores , Propriedades de Superfície , Transistores EletrônicosRESUMO
Emulation of human sensory and motor functions becomes a core technology in bioinspired electronics for next-generation electronic prosthetics and neurologically inspired robotics. An electronic synapse functionalized with an artificial sensory receptor and an artificial motor unit can be a fundamental element of bioinspired soft electronics. Here, we report an organic optoelectronic sensorimotor synapse that uses an organic optoelectronic synapse and a neuromuscular system based on a stretchable organic nanowire synaptic transistor (s-ONWST). The voltage pulses of a self-powered photodetector triggered by optical signals drive the s-ONWST, and resultant informative synaptic outputs are used not only for optical wireless communication of human-machine interfaces but also for light-interactive actuation of an artificial muscle actuator in the same way that a biological muscle fiber contracts. Our organic optoelectronic sensorimotor synapse suggests a promising strategy toward developing bioinspired soft electronics, neurologically inspired robotics, and electronic prostheses.
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Nanofios/química , Junção Neuromuscular/fisiologia , Monitoração Neuromuscular/instrumentação , Polímeros/química , Sinapses/fisiologia , Transistores Eletrônicos , Dispositivos Eletrônicos Vestíveis , Eletrônica , Humanos , Modelos NeurológicosRESUMO
An electronic (e-) skin is expected to experience significant wear and tear over time. Therefore, self-healing stretchable materials that are simultaneously soft and with high fracture energy, that is high tolerance of damage or small cracks without propagating, are essential requirements for the realization of robust e-skin. However, previously reported elastomers and especially self-healing polymers are mostly viscoelastic and lack high mechanical toughness. Here, a new class of polymeric material crosslinked through rationally designed multistrength hydrogen bonding interactions is reported. The resultant supramolecular network in polymer film realizes exceptional mechanical properties such as notch-insensitive high stretchability (1200%), high toughness of 12 000 J m-2 , and autonomous self-healing even in artificial sweat. The tough self-healing materials enable the wafer-scale fabrication of robust and stretchable self-healing e-skin devices, which will provide new directions for future soft robotics and skin prosthetics.
Assuntos
Elastômeros/química , Ligação de Hidrogênio , Polímeros , Água , Dispositivos Eletrônicos VestíveisRESUMO
A novel polymeric prodrug (PXPEG) was prepared to enhance the solubility of an anti-cancer drug, paclitaxel, in aqueous solutions and decrease the cytotoxicity by PEGylation, which means PEG attached to another molecule. In addition, the targeting ligand, transferrin (TF), was modified to PXPEG to enhance the therapeutic efficacy. The targeting ligand-modified PXPEG (TFPXPEG) was examined by (1)H-NMR to confirm the successful synthesis. The synthesized TFPXPEG had better solubility than the free drug against aqueous solution. The particle size of TFPXPEG was approximately 197.2nm and it had a spherical shape. The MTT assay showed that the anti-tumor efficiency of TFPXPEG was better than that of TF-unmodified PXPEG. In the KB tumor-bearing mouse model, the tumor volume of TFPXPEG treated groups was decreased dramatically by more than 2 fold or 3 fold compared to the PBS or PXPEG treated groups. The in vitro and in vivo evaluation showed that TFPXPEG had better efficacy than that of PXPEG due to the targeting effect of targeting ligands, such as TF.