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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 -
Soft Robotics Feb 2021Current additive manufacturing, including three-dimensional (3D) and so-called four-dimensional printing, of soft robotic devices is limited to millimeter sizes. In this...
Current additive manufacturing, including three-dimensional (3D) and so-called four-dimensional printing, of soft robotic devices is limited to millimeter sizes. In this study, we present additive manufacturing of soft microactuators and microrobots to fabricate even smaller structures in the micrometer domain. Using a custom-built extrusion 3D printer, microactuators are scaled down to a size of 300 × 1000 μm, with minimum thickness of 20 μm. Microactuators combined with printed body and electroactive polymers to drive the actuators are fabricated from computer-aided design model of the device structure. To demonstrate the ease and versatility of 3D printing process, microactuators with varying lengths ranging from 1000 to 5000 μm are fabricated and operated. Likewise, microrobotic devices consisting of a rigid body and individually controlled free-moving arms or legs are 3D printed to explore the microfabrication of soft grippers, manipulators, or microrobots through simple additive manufacturing technique.
Topics: Microtechnology; Polymers; Printing, Three-Dimensional; Robotics
PubMed: 32326869
DOI: 10.1089/soro.2019.0129 -
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 -
Molecular Microbiology Mar 2022Advances in microfabrication technology, and its increasing accessibility, allow us to explore fungal biology as never before. By coupling molecular genetics with... (Review)
Review
Advances in microfabrication technology, and its increasing accessibility, allow us to explore fungal biology as never before. By coupling molecular genetics with fluorescence live-cell imaging in custom-designed chambers, we can now probe single yeast cell responses to changing conditions over a lifetime, characterise population heterogeneity and investigate its underlying causes. By growing filamentous fungi in complex physical environments, we can identify cross-species commonalities, reveal species-specific growth responses and examine physiological differences relevant to diverse fungal lifestyles. As affordability and expertise broadens, microfluidic platforms will become a standard technique for examining the role of fungi in cross-kingdom interactions, ranging from rhizosphere to microbiome to interconnected human organ systems. This review brings together the perspectives already gained from studying fungal biology in microfabricated systems and outlines their potential in understanding the role of fungi in the environment, health and disease.
Topics: Biology; Fungi; Humans; Microtechnology; Rhizosphere; Saccharomyces cerevisiae
PubMed: 34592794
DOI: 10.1111/mmi.14816 -
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 -
Current Opinion in Biotechnology Feb 2014Micro-scale biological tools that have allowed probing of individual cells--from the genetic, to proteomic, to phenotypic level--have revealed important contributions of... (Review)
Review
Micro-scale biological tools that have allowed probing of individual cells--from the genetic, to proteomic, to phenotypic level--have revealed important contributions of single cells to direct normal and diseased body processes. In analyzing single cells, sample heterogeneity between and within specific cell types drives the need for high-throughput and quantitative measurement of cellular parameters. In recent years, high-throughput single-cell analysis platforms have revealed rare genetic subpopulations in growing tumors, begun to uncover the mechanisms of antibiotic resistance in bacteria, and described the cell-to-cell variations in stem cell differentiation and immune cell response to activation by pathogens. This review surveys these recent technologies, presenting their strengths and contributions to the field, and identifies needs still unmet toward the development of high-throughput single-cell analysis tools to benefit life science research and clinical diagnostics.
Topics: Animals; High-Throughput Screening Assays; Humans; Microtechnology; Neoplasms; Proteomics; Single-Cell Analysis; Stem Cells
PubMed: 24484889
DOI: 10.1016/j.copbio.2013.09.005 -
Biotechnology Journal Jan 2014Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and... (Review)
Review
Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and pharmaceutical research. Here we review the recent development of microengineered physiological systems, or also known as "ogans-on-chips", that reconstitute the physiologically critical features of specific human tissues and organs and their interactions. This technology uses microengineering approaches to construct organ-specific microenvironments, reconstituting tissue structures, tissue-tissue interactions and interfaces, and dynamic mechanical and biochemical stimuli found in specific organs, to direct cells to assemble into functional tissues. We first discuss microengineering approaches to reproduce the key elements of physiologically important, dynamic mechanical microenvironments, biochemical microenvironments, and microarchitectures of specific tissues and organs in microfluidic cell culture systems. This is followed by examples of microengineered individual organ models that incorporate the key elements of physiological microenvironments into single microfluidic cell culture systems to reproduce organ-level functions. Finally, microengineered multiple organ systems that simulate multiple organ interactions to better represent human physiology, including human responses to drugs, is covered in this review. This emerging organs-on-chips technology has the potential to become an alternative to 2D and 3D cell culture and animal models for experimental medicine, human disease modeling, drug development, and toxicology.
Topics: Animals; Cellular Microenvironment; Human Umbilical Vein Endothelial Cells; Humans; Microfluidic Analytical Techniques; Microtechnology; Models, Biological; Precision Medicine; Tissue Culture Techniques; Tissue Engineering
PubMed: 24357624
DOI: 10.1002/biot.201300187 -
Advanced Drug Delivery Reviews 2020Orally ingestible medical devices provide significant advancement for diagnosis and treatment of gastrointestinal (GI) tract-related conditions. From micro- to... (Review)
Review
Orally ingestible medical devices provide significant advancement for diagnosis and treatment of gastrointestinal (GI) tract-related conditions. From micro- to macroscale devices, with designs ranging from very simple to complex, these medical devices can be used for site-directed drug delivery in the GI tract, real-time imaging and sensing of gut biomarkers. Equipped with uni-direction release, or self-propulsion, or origami design, these microdevices are breaking the barriers associated with drug delivery, including biologics, across the GI tract. Further, on-board microelectronics allow imaging and sensing of gut tissue and biomarkers, providing a more comprehensive understanding of underlying pathophysiological conditions. We provide an overview of recent advances in orally ingestible medical devices towards drug delivery, imaging and sensing. Challenges associated with gut microenvironment, together with various activation/actuation modalities of medical devices for micromanipulation of the gut are discussed. We have critically examined the relationship between materials-device design-pharmacological responses with respect to existing regulatory guidelines and provided a clear roadmap for the future.
Topics: Administration, Oral; Biomarkers; Delayed-Action Preparations; Drug Delivery Systems; Equipment and Supplies; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Hydrogen-Ion Concentration; Microtechnology; Nanoparticles
PubMed: 32416112
DOI: 10.1016/j.addr.2020.05.004 -
Biomedical Microdevices Aug 2019Conventional skin and blood sampling techniques for disease diagnosis, though effective, are often highly invasive and some even suffer from variations in analysis. With... (Review)
Review
Conventional skin and blood sampling techniques for disease diagnosis, though effective, are often highly invasive and some even suffer from variations in analysis. With the improvements in molecular detection, the amount of starting sample quantity needed has significantly reduced in some diagnostic procedures, and this has led to an increased interest in microsampling techniques for disease biomarker detection. The miniaturization of sampling platforms driven by microsampling has the potential to shift disease diagnosis and monitoring closer to the point of care. The faster turnaround time for actionable results has improved patient care. The variations in sample quantification and analysis remain a challenge in the microsampling field. The future of microsampling looks promising. Emerging techniques are being clinically tested and monitored by regulatory bodies. This process is leading to safer and more reliable diagnostic platforms. This review discusses the advantages and disadvantages of current skin and blood microsampling techniques.
Topics: Animals; Blood; Humans; Microtechnology; Point-of-Care Systems; Skin
PubMed: 31418068
DOI: 10.1007/s10544-019-0412-y -
Cellular and Molecular Gastroenterology... 2019
Topics: Animals; Cell Culture Techniques; Humans; Microtechnology; Organ Specificity; Organoids; Pluripotent Stem Cells; Tissue Engineering
PubMed: 30831074
DOI: 10.1016/j.jcmgh.2019.02.005