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Advanced Healthcare Materials Jan 2018In the drug development process, the accurate prediction of drug efficacy and toxicity is important in order to reduce the cost, labor, and effort involved. For this... (Review)
Review
In the drug development process, the accurate prediction of drug efficacy and toxicity is important in order to reduce the cost, labor, and effort involved. For this purpose, conventional 2D cell culture models are used in the early phase of drug development. However, the differences between the in vitro and the in vivo systems have caused the failure of drugs in the later phase of the drug-development process. Therefore, there is a need for a novel in vitro model system that can provide accurate information for evaluating the drug efficacy and toxicity through a closer recapitulation of the in vivo system. Recently, the idea of using microtechnology for mimicking the microscale tissue environment has become widespread, leading to the development of "organ-on-a-chip." Furthermore, the system is further developed for realizing a multiorgan model for mimicking interactions between multiple organs. These advancements are still ongoing and are aimed at ultimately developing "body-on-a-chip" or "human-on-a-chip" devices for predicting the response of the whole body. This review summarizes recently developed organ-on-a-chip technologies, and their applications for reproducing multiorgan functions.
Topics: Animals; Humans; Lab-On-A-Chip Devices; Microtechnology; Models, Biological; Organ Culture Techniques
PubMed: 28945001
DOI: 10.1002/adhm.201700419 -
Biofabrication Jun 2019Biofabrication techniques have enabled the formation of complex models of many biological tissues. We present a framework to contextualize biofabrication techniques... (Review)
Review
Biofabrication techniques have enabled the formation of complex models of many biological tissues. We present a framework to contextualize biofabrication techniques within a disease modeling application. Fibrosis is a progressive disease interfering with tissue structure and function, which stems from an aberrant wound healing response. Epithelial injury and clot formation lead to fibroblast invasion and activation, followed by contraction and remodeling of the extracellular matrix. These stages have healthy wound healing variants in addition to the pathogenic analogs that are seen in fibrosis. This review evaluates biofabrication of a variety of phenotypic cell-based fibrosis assays. By recapitulating different contributors to fibrosis, these assays are able to evaluate biochemical pathways and therapeutic candidates for specific stages of fibrosis pathogenesis. Biofabrication of these culture models may enable phenotypic screening for improved understanding of fibrosis biology as well as improved screening of anti-fibrotic therapeutics.
Topics: Animals; Biological Assay; Fibroblasts; Humans; Microtechnology; Models, Biological; Phenotype; Pulmonary Fibrosis
PubMed: 31215521
DOI: 10.1088/1758-5090/ab2286 -
Biomedical Microdevices Aug 2019Untethered microgrippers that can navigate in hard-to-reach and unpredictable environments are significantly important for biomedical applications such as targeted drug... (Review)
Review
Untethered microgrippers that can navigate in hard-to-reach and unpredictable environments are significantly important for biomedical applications such as targeted drug delivery, micromanipulation, minimally invasive surgery and in vivo biopsy. Compared with the traditional tethered microgrippers, the wireless microgrippers, due to the exceptional characteristics such as miniaturized size, untethered actuation, dexterous and autonomous motion, are projected to be promising microtools in various future applications. In this review, we categorize the untethered microgrippers into five major classes, i.e. microgrippers responsive to thermal, microgrippers actuated by magnetic fields, microgrippers responsive to chemicals, light-driven microgrippers and hybrid actuated microgrippers. Firstly, the actuation mechanisms of these microgrippers are introduced. The challenges faced by these microgrippers are also covered in this part. With that, the fabrication methods of these microgrippers are summarized. Subsequently, the applications of microgrippers are presented. Additionally, we conduct a comparison among different actuation mechanisms to explore the advantages and potential challenges of various types of microgrippers. In the end of this review, conclusions and outlook of the development and potential applications of the microgrippers are discussed.
Topics: Biomimetics; Hand; Humans; Microtechnology; Robotics; Temperature
PubMed: 31418070
DOI: 10.1007/s10544-019-0430-9 -
Biomedical Microdevices Sep 2017Micro and nano technologies are of increasing importance in microfluidics devices used for electroporation (electroporation - the permeabilization of the cell membrane...
Micro and nano technologies are of increasing importance in microfluidics devices used for electroporation (electroporation - the permeabilization of the cell membrane with brief high electric field pulses). Electrochemical reactions of electrolysis occur whenever an electric current flows between an electrode and an ionic solution. It can have substantial detrimental effects, both on the cells and solutions during the electroporation. As electrolysis is a surface phenomenon, between electrodes and solution, the extent of electrolysis is increased in micro and nano electroporation over macro-electroporation, because the surface area of the electrodes in micro and nano electroporation is much larger. A possible way to eliminate the electrolytic effect is to develop non-electrolytic microelectroporation by coating the microelectroporation devices with a dielectric insulating layer. In this study, we examine the effect of a dielectric insulating layer on the performance of a singularity microelectroporation device that we have recently designed. Using numerical analysis, we study the effects of various design parameters including, input sinusoidal voltage amplitude and frequency, geometrical configuration and material electrical properties on the electroporation performance of the non-electrolytic microelectroporation device. In the simulation, we used properties of four real dielectric materials and four solutions of interest for microelectroporation. We characterized the effect of various design parameters of relevance to singularity based microelectroporation, on non-electrolytic microelectroporation. Interestingly, we found that the system behaves in some aspects as a filter and in many circumstances saturation of performance is reached. After saturation is reached, changes in parameters will not affect the performance of the device.
Topics: Electroporation; Equipment Design; Microtechnology
PubMed: 28710644
DOI: 10.1007/s10544-017-0204-1 -
Lab on a Chip Apr 2020Electrochemistry provides possibilities to realize smart microdevices of the next generation with high functionalities. Electrodes, which constitute major components of... (Review)
Review
Electrochemistry provides possibilities to realize smart microdevices of the next generation with high functionalities. Electrodes, which constitute major components of electrochemical devices, can be formed by various microfabrication techniques, and integration of the same (or different) components for that purpose is not difficult. Merging this technique with microfluidics can further expand the areas of application of the resultant devices. To augment the development of next generation devices, it will be beneficial to review recent technological trends in this field and clarify the directions required for moving forward. Even when limiting the discussion to electrochemical microdevices, a variety of useful techniques should be considered. Therefore, in this review, we attempted to provide an overview of all relevant techniques in this context in the hope that it can provide useful comprehensive information.
Topics: Electrochemistry; Electrodes; Microtechnology
PubMed: 32129358
DOI: 10.1039/c9lc01112a -
Current Opinion in Otolaryngology &... Oct 2020Treatment of auditory dysfunction is dependent on inner ear drug delivery, with microtechnologies playing an increasingly important role in cochlear access and... (Review)
Review
PURPOSE OF REVIEW
Treatment of auditory dysfunction is dependent on inner ear drug delivery, with microtechnologies playing an increasingly important role in cochlear access and pharmacokinetic profile control. This review examines recent developments in the field for clinical and animal research environments.
RECENT FINDINGS
Micropump technologies are being developed for dynamic control of flow rates with refillable reservoirs enabling timed delivery of multiple agents for protection or regeneration therapies. These micropumps can be combined with cochlear implants with integral catheters or used independently with cochleostomy or round window membrane (RWM) delivery modalities for therapy development in animal models. Sustained release of steroids with coated cochlear implants remains an active research area with first-time-in-human demonstration of reduced electrode impedances. Advanced coatings containing neurotrophin producing cells have enhanced spiral ganglion neuron survival in animal models, and have proven safe in a human study. Microneedles have emerged for controlled microperforation of the RWM for significant enhancement in permeability, combinable with emerging matrix formulations that optimize biological interaction and drug release kinetics.
SUMMARY
Microsystem technologies are providing enhanced and more controlled access to the inner ear for advanced drug delivery approaches, alone and in conjunction with cochlear implants.
Topics: Animals; Drug Delivery Systems; Ear, Inner; Humans; Microtechnology
PubMed: 32796268
DOI: 10.1097/MOO.0000000000000648 -
Lab on a Chip Nov 2016Micro-/nanofabrication-based lab-on-a-chip (LOC) technologies have recently been substantially advanced and have become widely used in various inter-/multidisciplinary... (Review)
Review
Micro-/nanofabrication-based lab-on-a-chip (LOC) technologies have recently been substantially advanced and have become widely used in various inter-/multidisciplinary research fields, including biological, (bio-)chemical, and biomedical fields. However, such hybrid-scale LOC devices are typically fabricated using microfabrication and nanofabrication processes in series, resulting in increased cost and time and low throughput issues. In this review, after briefly introducing the conventional micro-/nanofabrication technologies, we focus on unconventional micro-/nanofabrication technologies that allow us to produce either in situ micro-/nanoscale structures or master molds for additional replication processes to easily and conveniently create novel LOC devices with micro- or nanofluidic channel networks. In particular, microfabrication methods based on crack-assisted photolithography and carbon-microelectromechanical systems (C-MEMS) are described in detail because of their superior features from the viewpoint of the throughput, batch fabrication process, and mixed-scale channels/structures. In parallel with previously reported articles on conventional micro-/nanofabrication technologies, our review of unconventional micro-/nanofabrication technologies will provide a useful and practical fabrication guideline for future hybrid-scale LOC devices.
Topics: Lab-On-A-Chip Devices; Microtechnology; Nanotechnology; Nanowires; Printing
PubMed: 27761529
DOI: 10.1039/c6lc01058j -
Biofabrication Jun 2019Skeletal muscle is a tissue with a complex and hierarchical architecture that influences its functional properties. In order to exert its contractile function, muscle... (Review)
Review
Skeletal muscle is a tissue with a complex and hierarchical architecture that influences its functional properties. In order to exert its contractile function, muscle tissue is connected to neural, vascular and connective compartments, comprising finely structured interfaces which are orchestrated by multiple signalling pathways. Pathological conditions such as dystrophies and trauma, or physiological situations such as exercise and aging, modify the architectural organization of these structures, hence affecting muscle functionality. To overcome current limitations of in vivo and standard in vitro models, microfluidics and biofabrication techniques have been applied to better reproduce the microarchitecture and physicochemical environment of human skeletal muscle tissue. In the present review, we aim to critically discuss the role of those techniques, taken individually or in combination, in the generation of models that mimic the complex interfaces between muscle tissue and neural/vascular/tendon compartments. The exploitation of either microfluidics or biofabrication to model different muscle interfaces has led to the development of constructs with an improved spatial organization, thus presenting a better functionality as compared to standard models. However, the achievement of models replicating muscle-tissue interfaces with adequate architecture, presence of fundamental proteins and recapitulation of signalling pathways is still far from being achieved. Increased integration between microfluidics and biofabrication, providing the possibility to pattern cells in predetermined structures with higher resolution, will help to reproduce the hierarchical and heterogeneous structure of skeletal muscle interfaces. Such strategies will further improve the functionality of these techniques, providing a key contribution towards the study of skeletal muscle functions in physiology and pathology.
Topics: Animals; Humans; Microtechnology; Models, Biological; Muscle, Skeletal; Tendons; Tissue Engineering
PubMed: 31042682
DOI: 10.1088/1758-5090/ab1e7c -
Advanced Drug Delivery Reviews 2020Oral administration is a pillar of the pharmaceutical industry and yet it remains challenging to administer hydrophilic therapeutics by the oral route. Smart and... (Review)
Review
Oral administration is a pillar of the pharmaceutical industry and yet it remains challenging to administer hydrophilic therapeutics by the oral route. Smart and controlled oral drug delivery could bypass the physiological barriers that limit the oral delivery of these therapeutics. Micro- and nanoscale technologies, with an unprecedented ability to create, control, and measure micro- or nanoenvironments, have found tremendous applications in biology and medicine. In particular, significant advances have been made in using these technologies for oral drug delivery. In this review, we briefly describe biological barriers to oral drug delivery and micro and nanoscale fabrication technologies. Micro and nanoscale drug carriers fabricated using these technologies, including bioadhesives, microparticles, micropatches, and nanoparticles, are described. Other applications of micro and nanoscale technologies are discussed, including fabrication of devices and tissue engineering models to precisely control or assess oral drug delivery in vivo and in vitro, respectively. Strategies to advance translation of micro and nanotechnologies into clinical trials for oral drug delivery are mentioned. Finally, challenges and future prospects on further integration of micro and nanoscale technologies with oral drug delivery systems are highlighted.
Topics: Administration, Oral; Animals; Drug Carriers; Drug Delivery Systems; Humans; Hydrophobic and Hydrophilic Interactions; Microspheres; Microtechnology; Nanoparticles; Nanotechnology; Pharmaceutical Preparations
PubMed: 32707147
DOI: 10.1016/j.addr.2020.07.012 -
Journal of Biomedical Science Oct 2019Engineering approaches were adopted for liver microsystems to recapitulate cell arrangements and culture microenvironments in vivo for sensitive, high-throughput and... (Comparative Study)
Comparative Study Review
Engineering approaches were adopted for liver microsystems to recapitulate cell arrangements and culture microenvironments in vivo for sensitive, high-throughput and biomimetic drug screening. This review introduces liver microsystems in vitro for drug hepatotoxicity, drug-drug interactions, metabolic function and enzyme induction, based on cell micropatterning, hydrogel biofabrication and microfluidic perfusion. The engineered microsystems provide varied microenvironments for cell culture that feature cell coculture with non-parenchymal cells, in a heterogeneous extracellular matrix and under controllable perfusion. The engineering methods described include cell micropatterning with soft lithography and dielectrophoresis, hydrogel biofabrication with photolithography, micromolding and 3D bioprinting, and microfluidic perfusion with endothelial-like structures and gradient generators. We discuss the major challenges and trends of liver microsystems to study drug response in vitro.
Topics: Cell Engineering; Drug Evaluation, Preclinical; Humans; Liver; Microtechnology; Pharmaceutical Preparations
PubMed: 31660980
DOI: 10.1186/s12929-019-0575-0