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The emergence of micro/nanomaterials in recent decades has brought promising alternative approaches in various biomedicine-related fields such as pharmaceutics, diagnostics, and therapeutics. These micro/nanomaterials for specific biomedical applications shall possess tailored properties and functionalities that are closely correlated to their geometries, structures, and compositions, therefore placing extremely high demands for manufacturing techniques. Owing to the superior capabilities in manipulating fluids and droplets at microscale, microfluidics has offered robust and versatile platform technologies enabling rational design and fabrication of micro/nanomaterials with precisely controlled geometries, structures and compositions in high throughput manners, making them excellent candidates for a variety of biomedical applications. This review briefly summarizes the progress of microfluidics in the fabrication of various micro/nanomaterials ranging from 0D (particles), 1D (fibers) to 2D/3D (film and bulk materials) materials with controllable geometries, structures, and compositions. The applications of these microfluidic-based materials in the fields of diagnostics, drug delivery, organs-on-chips, tissue engineering, and stimuli-responsive biodevices are introduced. Finally, an outlook is discussed on the future direction of microfluidic platforms for generating materials with superior properties and on-demand functionalities. The integration of new materials and techniques with microfluidics will pave new avenues for preparing advanced micro/nanomaterials with enhanced performance for biomedical applications.
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Microfluídica , Nanoestruturas , Sistemas de Liberação de Medicamentos , Microfluídica/instrumentação , Microfluídica/tendências , Nanoestruturas/química , Engenharia TecidualRESUMO
The etching of colloidal silica by hot water provides a green chemistry method for the preparation of mesoporous silica. Nevertheless, the reaction mechanism of this etching process has not been elucidated and its reproducibility is often questionable, which has hindered its widespread application in the preparation of mesoporous silica materials. Herein, we present a systematic study on the hot-water etching of sol-gel derived silica shells coated on α-Fe2O3 particles. Transmission electron microscopy and infrared spectroscopy studies provide substantial evidence that colloidal silica with low hydrolysis and condensation degrees (or aging degrees) is preferentially etched by hot water. More importantly, we show that the aging degree of silica shells, which determines the etching rate, can be precisely tuned by controlling the sol-gel preparation time and the storage time in room-temperature water prior to hot-water etching. These results provide novel insights into the physicochemical properties of sol-gel derived colloidal silica and the mechanistic understanding of the reaction kinetics of silica etching by hot water.
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Droplet manipulation plays a critical role in both fundamental research and practical applications, especially when combined with smart materials and external fields to achieve multifunctional droplet manipulation. Light control of droplets has emerged as a significant and widely used strategy, driven primarily by photochemistry, photomechanics, light-induced Marangoni effects, and light-induced electric effects. This approach allowing for droplet manipulation with high spatial and temporal resolution, all while maintaining a remote and non-contact mode of operation. This review aims to provide a comprehensive overview of the mechanisms underlying light control of droplets, the design of smart materials for this purpose, and the diverse range of applications enabled by this technique. These applications include merging, splitting, releasing, forwarding, backward movement, and rotation of droplets, as well as chemical reactions, droplet robots, and microfluidics. By presenting this information, we aim to establish a unified framework that guides the sustainable development of light control of droplets. Additionally, this review addresses the challenges associated with light control of droplets and suggests potential directions for future development.
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Human body tissues such as muscle, blood vessels, tendon/ligaments, and nerves have fiber-like fascicle morphologies, where ordered organization of cells and extracellular matrix (ECM) within the bundles in specific 3D manners orchestrates cells and ECM to provide tissue functions. Through engineering cell fibers (which are fibers containing living cells) as living building blocks with the help of emerging "bottom-up" biomanufacturing technologies, it is now possible to reconstitute/recreate the fiber-like fascicle morphologies and their spatiotemporally specific cell-cell/cell-ECM interactions in vitro, thereby enabling the modeling, therapy, or repair of these fibrous tissues. In this article, a concise review is provided of the "bottom-up" biomanufacturing technologies and materials usable for fabricating cell fibers, with an emphasis on electrospinning that can effectively and efficiently produce thin cell fibers and with properly designed processes, 3D cell-laden structures that mimic those of native fibrous tissues. The importance and applications of cell fibers as models, therapeutic platforms, or analogs/replacements for tissues for areas such as drug testing, cell therapy, and tissue engineering are highlighted. Challenges, in terms of biomimicry of high-order hierarchical structures and complex dynamic cellular microenvironments of native tissues, as well as opportunities for cell fibers in a myriad of biomedical applications, are discussed.
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Tissue engineering and regenerative medicine have offered promising alternatives for clinical treatment of body tissue traumas, losses, dysfunctions, or diseases, where scaffold-based strategies are particularly popular and effective. Over the decades, scaffolds for tissue regeneration have been remarkably evolving. Nevertheless, conventional scaffolds still confront grand challenges in bio-adaptions in terms of both tissue-scaffold and cell-scaffold interplays, for example complying with complicated three-dimensional (3D) shapes of biological tissues and recapitulating the ordered cell regulation effects of native cell microenvironments. Benefiting from the recent advances in "intelligent" biomaterials, reconfigurable scaffolds have been emerging, demonstrating great promise in addressing the bio-adaption challenges through altering their macro-shapes and/or micro-structures. This mini-review article presents a brief overview of the cutting-edge research on reconfigurable scaffolds, summarizing the materials for forming reconfigurable scaffolds and highlighting their applications for adaptive tissue regeneration. Finally, the challenges and prospects of reconfigurable scaffolds are also discussed, shedding light on the bright future of next-generation reconfigurable scaffolds with upgrading adaptability.
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Materiais Biocompatíveis , Alicerces Teciduais , Alicerces Teciduais/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Engenharia Tecidual , Medicina Regenerativa , CicatrizaçãoRESUMO
Vaccines are undoubtedly a powerful weapon in our fight against global pandemics, as demonstrated in the recent COVID-19 case, yet they often face significant challenges in reliable cold chain transport. Despite extensive efforts to monitor their time-temperature history, current time-temperature indicators (TTIs) suffer from limited reliability and stability, such as difficulty in avoiding human intervention, inapplicable to subzero temperatures, narrow tracking temperature ranges, or susceptibility to photobleaching. Herein, we develop a class of structural color materials that harnesses dual merits of fluidic nature and structural color, enabling thermal-triggered visible color destruction based on triggering agent-diffusion-induced irreversible disassembly of liquid colloidal photonic crystals for indicating the time-temperature history of the cold chain transport. These self-destructive structural color liquids (SCLs) exhibit inherent irreversibility, superior sensitivity, tunable self-destructive time (minutes to days), and a wide tracking temperature range (-70 to +37 °C). Such self-destructive SCLs can be conveniently packaged into flexible TTIs for monitoring the storage and exposure status of diverse vaccines via naked-eye inspection or mobile phone scanning. By overcoming the shortcomings inherent in conventional TTIs and responsive photonic crystals, these self-destructive SCLs can increase their compatibility with cold chain transport and hold promise for the development and application of the next-generation intelligent TTIs and photonic crystals.
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COVID-19 , Humanos , Temperatura , Cor , Reprodutibilidade dos Testes , FótonsRESUMO
The manipulation of droplets plays a vital role in fundamental research and practical applications, from chemical reactions to bioanalysis. As an intriguing and active format, light control of droplets, typically induced by photochemistry, photomechanics, light-induced Marangoni effects or light-induced electric fields, enables remote and contactless control with remarkable spatial and temporal accuracy. However, current light control of droplets suffers from poor performance and limited reliability. Here we develop a new superamphiphobic material that integrates the dual merits of light and electric field by rationally preparing liquid metal particles/poly(vinylidene fluoride-trifluoroethylene) polymer composites with photo-induced charge generation capability in real time, enabling light control of droplets on the basis of photo-induced dielectrophoretic force. We demonstrate that this photo-induced charged surface (PICS) imparts a new paradigm for controllable droplet motion, including high average velocity (â¼35.9 mm s-1), unlimited distance, multimode motions (e.g. forward, backward and rotation) and single-to-multiple droplet manipulation, which are otherwise unachievable in conventional strategies. We further extend light control of droplets to robotic and bio-applications, including transporting a solid cargo in a closed tube, crossing a tiny tunnel, avoiding obstacles, sensing the changing environment via naked-eye color shift, preparing hydrogel beads, transporting living cells and reliable biosensing. Our PICS not only provides insight into the development of new smart interface materials and microfluidics, but also brings new possibilities for chemical and biomedical applications.
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The cuff electrode can be wrapped in the columnar or tubular biological tissue for physiological signal detection or stimulation regulation. The reliable and non-excessive interfaces between the electrode and complex tissue are critical. Here, we propose a self-closing stretchable cuff electrode, which is able to self-close onto the bundles of tissues after dropping water. The curliness is realized by the mechanical stress mismatch between different layers of the elastic substrate. The material of the substrate can be selected to match the modulus of the target tissue to achieve minimal constraint on the tissue. Moreover, the self-closing structure keeps the cuff electrode free from any extra mechanical locking structure. For in vivo testing, both sciatic nerve stimulation to drive muscles and electromyographic signal monitoring around a rat's extensor digitorum longus for 1 month prove that our proposed electrode conforms well to the curved surface of biological tissue.
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Músculo Esquelético , Nervo Isquiático , Ratos , Animais , Estimulação Elétrica , Nervo Isquiático/fisiologia , Eletrodos , Músculo Esquelético/fisiologia , Eletrodos ImplantadosRESUMO
Reliable functions of medical implants highly depend on biocompatible, conformal, and stable biointerfaces for seamless biointegration with biological tissues. Though flexible biointerfaces based on synthetic hydrogels have shown promise in optimizing implant biointegration via surgical suturing, physical attachment, or manual preshaping, they still suffer from poor adaptability, such as tissue damage by surgical suturing, low bioactivity, and difficulties in conformal contact and stable fixation, especially for specific tissues of large surface curvatures. Here, we report a bilayer hydrogel-based adaptive biointerface (HAB) made of two polysaccharide derivates, N-hydroxysuccinimide (NHS) ester-activated alginate and chitosan, harnessing dual advantages of their different swelling and active groups. Leveraging on the differential swelling between the two hydrogel layers and covalent linkages with active groups at hydrogel interfaces, HABs can be programmed into sealed tubes with tunable diameters via water-induced compliable shape morphing and instant interfacial adhesion. We further demonstrate that the polysaccharide-based morphing-to-adhesion HAB possesses outstanding bioactivity in directing cellular focal adhesion and intercellular junction, versatile geometrical adaptability to diverse tubular tissues with a wide range of surface curvatures (2.8 × 102-1.3 × 103 m-1), and excellent mechanical stability in high load-/shear-bearing physiological environments (blood flow volume: 85 mm·s-1). HABs overcome the limitations of existing biointerfaces in terms of poor bioactivity and difficult biointegration with biological tissues of large surface curvatures, holding promise to open new avenues for adaptive biointerfaces and reliable medical implants.
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Quitosana , Hidrogéis , Alginatos , Ésteres , Humanos , Hidrogéis/farmacologia , Aderências Teciduais , ÁguaRESUMO
Slippery lubricant-infused porous (SLIPS) and superhydrophobic surfaces have emerged as promising interfacial materials for various applications such as self-cleaning, anti-icing, and antifouling. Paradoxically, the coverage/screening of lubricant layer on underlying rough matrix endows functionalities impossible on superhydrophobic surfaces; however, the inherent flexibility in programming droplet manipulation through tailoring structure or surface charge gradient in underlying matrix is compromised. Here, we develop a class of slippery material that harnesses the dual advantages of both solid and lubricant. This is achieved by rationally constructing a photothermal-responsive composite matrix with real-time light-induced surface charge regeneration capability, enabling photocontrol of droplets in various working scenarios. We demonstrate that this light-induced charged slippery surface (LICS) exerts photocontrol of droplets with fast speed, long distance, antigravity motion, and directionally collective motion. We further extend the LICS to biomedical domains, ranging from specific morphological hydrogel bead formation in an open environment to biological diagnosis and analysis in closed-channel microfluidics.
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In nature, some creatures have the capability to change shapes to adapt to ever-changing environments, which greatly inspire researchers to develop soft actuators. To endow soft actuators with capabilities to interact with environment and integrate more feedbacks is of great significance. Colour-tunable soft actuators that provide colour change feedbacks have therefore attracted extensive attention. Based on either chemical-colour or structural-colour based materials, a variety of colour-tunable soft actuators enabling shape deformations (or locomotion) and colour changes have been prepared and hold promise for applications in soft robotics and biomedical devices. This review summarizes the recent advances of colour-tunable soft actuators, with emphasis on their colour-change mechanisms and highlighting their applications. Existing challenges and future perspectives on colour-tunable soft actuators are presented.
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[This corrects the article DOI: 10.1093/nsr/nwz188.].
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Shape-morphing hydrogels can be widely used to develop artificial muscles, reconfigurable biodevices, and soft robotics. However, conventional approaches for developing shape-morphing hydrogels highly rely on composite materials or complex manufacturing techniques, which limit their practical applications. Herein, we develop an unprecedented strategy to edit the shape morphing of monocomponent natural polysaccharide hydrogel films via integrating gradient cross-linking density and geometry effect. Owing to the synergistic effect, the shape morphing of chitosan (CS) hydrogel films with gradient cross-linking density can be facilely edited by changing their geometries (length-to-width ratios or thicknesses). Therefore, helix, short-side rolling, and long-side rolling can be easily customized. Furthermore, various complex artificial 3D deformations such as artificial claw, horn, and flower can also be obtained by combining various flat CS hydrogel films with different geometries into one system, which can further demonstrate various shape transformations as triggered by pH. This work offers a simple strategy to construct a monocomponent hydrogel with geometry-directing programmable deformations, which provides universal insights into the design of shape-morphing polymers and will promote their applications in biodevices and soft robotics.
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Octopus suckers that possess the ability to actively control adhesion through muscle actuation have inspired artificial adhesives for safe manipulation of thin and delicate objects. However, the design of adhesives with fast adhesion switching speed to transport cargoes in confined spaces remains an open challenge. Here, we present an untethered magnetic adhesive pad combining the functionality of fast adhesion switching and remotely controlled locomotion. The adhesive pad can be activated from low-adhesion state to high-adhesion state by near infrared laser within 30 s, allowing to fulfill a high-throughput task of retrieving and releasing objects. Moreover, under the guidance of external magnetic field, the proposed pad is demonstrated to transport thin and fragile electronic components across a tortuous path, thus indicating its potential for dexterous delivery in complex working environments.
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Adesivos , Locomoção , Eletrônica , Fenômenos Magnéticos , Fenômenos FísicosRESUMO
This communication describes a novel water-soluble membrane prepared from chitosan intended for SARS-CoV-2 viral nucleic acid collection and detection. The CSH membrane formed from nanofibers shows promising potential in the quantitative determination of the SARS-CoV-2 viral nucleic acids at a concentration of 102 copies per L in air. The sponge-like structure which allows gas to pass through for collection of viral nucleic acids potentially provides simple, fast, and reliable sampling as well as detection of various types of airborne viruses.
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COVID-19 , Ácidos Nucleicos , Humanos , RNA Viral , SARS-CoV-2 , Manejo de Espécimes , ÁguaRESUMO
Acoustic tweezers have great application prospects because they allow noncontact and noninvasive manipulation of microparticles in a wide range of media. However, the nontransparency and heterogeneity of media in practical applications complicate particle trapping and manipulation. In this study, we designed a 1.04 MHz 256-element 2D matrix array for 3D acoustic tweezers to guide and monitor the entire process using real-time 3D ultrasonic images, thereby enabling acoustic manipulation in nontransparent media. Furthermore, we successfully performed dynamic 3D manipulations on multiple microparticles using multifoci and vortex traps. We achieved 3D particle manipulation in heterogeneous media (through resin baffle and ex vivo macaque and human skulls) by introducing a method based on the time reversal principle to correct the phase and amplitude distortions of the acoustic waves. Our results suggest cutting-edge applications of acoustic tweezers such as acoustical drug delivery, controlled micromachine transfer, and precise treatment.
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Implantable neural interfaces and systems have attracted much attention due to their broad applications in treating diverse neuropsychiatric disorders. However, obtaining a long-term reliable implant-neural interface is extremely important but remains an urgent challenge due to the resulting acute inflammatory responses. Here, bioinspired microcone-array-based (MA) interfaces have been successfully designed, and their cytocompatibility with neurons and the inflammatory response have been explored. Compared with smooth control samples, MA structures cultured with neuronal cells result in much denser extending neurites, which behave similar to creepers, wrapping tightly around the microcones to form complex and interconnected neuronal networks. After further implantation in mouse brains for 6 weeks, the MA probes (MAPs) significantly reduced glial encapsulation and neuron loss around the implants, suggesting better neuron viability at the implant-neural interfaces than that of smooth probes. This bioinspired strategy for both enhanced glial resistance and neuron network formation via a specific structural design could be a platform technology that not only opens up avenues for next-generation artificial neural networks and brain-machine interfaces but also provides universal approaches to biomedical therapeutics.
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Point-of-care (POC) diagnosis is of great significance in offering precise and personalized treatment for patients with eye diseases. Contact lenses, as a kind of popular wearable device on the eye, provide a suitable platform for the integration of biosensors for the POC diagnosis of eye diseases. However, existing contact lens sensors usually involve complex electronics and circuits, the manufacturing of which is complicated and signal readout requires additional instruments. To realize the instrument-free detection of pathologically relevant signals of eye diseases, we successfully established a structurally coloured contact lens sensor with a tunable colour in this investigation, which can directly report changes in moisture and pressure that are critical signs for xerophthalmia and glaucoma diagnosis, respectively, by altering colours. Importantly, this structurally coloured contact lens sensor is made solely from a biocompatible hydrogel, without the addition of any chemical pigments, therefore exhibiting superior biosafety and wearing comfort for wearable applications. With both excellent biocompatibility and sensing capabilities, this structurally coloured contact lens sensors thus holds great promise for instrument-free ophthalmic health monitoring, which will benefit a large proportion of the population that have a high risk of eye disease.
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Materiais Biocompatíveis/química , Cor , Lentes de Contato , Glaucoma/diagnóstico , Hidrogéis/química , Sistemas Automatizados de Assistência Junto ao Leito , Animais , Humanos , Masculino , Tamanho da Partícula , Coelhos , Propriedades de Superfície , Dispositivos Eletrônicos VestíveisRESUMO
Emerging wearable and implantable biodevices have been significantly revolutionizing the diagnosis and treatment of disease. However, the geometrical mismatch between tissues and biodevices remains a great challenge for achieving optimal performances and functionalities for biodevices. Shape-adaptable biodevices enabling active compliance with human body tissues offer promising opportunities for addressing the challenge through programming their geometries on demand. This article reviews the design principles and control strategies for shape-adaptable biodevices with programmable shapes and actively compliant capabilities, which have offered innovative diagnostic/therapeutic tools and facilitated a variety of wearable and implantable applications. The state-of-the-art progress in applications of shape-adaptable biodevices in the fields of smart textiles, wound care, healthcare monitoring, drug and cell delivery, tissue repair and regeneration, nerve stimulation and recording, and biopsy and surgery, is highlighted. Despite the remarkable advances already made, shape-adaptable biodevices still confront many challenges on the road toward the clinic, such as enhanced intelligence for actively sensing and operating in response to physiological environments. Next-generation paradigms will shed light on future directions for extending the breadth and performance of shape-adaptable biodevices for wearable and implantable applications.
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Dispositivos Eletrônicos Vestíveis , Humanos , Próteses e Implantes , TêxteisRESUMO
Endothelialization is of great significance for vascular remodeling, as well as for the success of implanted vascular grafts/stents in cardiovascular disease treatment. However, desirable endothelialization on synthetic biomaterials remains greatly challenging owing to extreme difficulty in offering dynamic guidance on endothelial cell (EC) functions resembling the native extracellular matrix-mediated effects. Here, we demonstrate a bilayer platform with near-infrared-triggered transformable topographies, which can alter the geometries and functions of human ECs by tunable topographical cues in a remote-controlled manner, yet cause no damage to the cell viability. The migration and the adhesion/spreading of human ECs are respectively promoted by the temporary anisotropic and permanent isotropic topographies of the platform in turn, which appropriately meet the requirements of stage-specific EC manipulation for endothelialization. In addition to the potential of promoting the development of a new generation of vascular grafts/stents enabling rapid endothelialization, this stage-specific cell-manipulation platform also holds promise in various biomedical fields, since the needs for stepwise control over different cell functions are common in wound healing and various tissue-regeneration processes.