A microfluidic device to perfuse pancreatic islets while simultaneously characterizing their functionality through fluorescence imaging of the mitochondrial membrane potential and intracellular calcium ([Ca2+]i) in addition to enzyme linked immunosorbent assay (ELISA) quantification of secreted insulin was developed and characterized. This multimodal characterization of islet function will facilitate rapid assessment of tissue quality immediately following isolation from donor pancreas and allow more informed transplantation decisions to be made which may improve transplantation outcomes. The microfluidic perfusion chamber allows flow rates of up to 1 mL/min, without any noticeable perturbation or shear of islets. This multimodal quantification was done on both mouse and human islets. The ability of this simple microfluidic device to detect subtle variations in islet responses in different functional assays performed in short time-periods demonstrates that the microfluidic perfusion chamber device can be used as a new gold standard to perform comprehensive islet analysis and obtain a more meaningful predictive value for islet functionality prior to transplantation into recipients, which is currently difficult to predict using a single functional assay.
An emerging approach for design of dynamic materials involves mimicking natural systems, which are adept at changing their structure and function in response to their environment. Biological systems possess a diverse range of dynamic mechanisms, including competitive ligand–protein binding, enzyme‐catalyzed remodeling, and allosteric protein conformational changes. These dynamic mechanisms are now being exploited by materials scientists and engineers to design “bioinspired” synthetic materials that undergo responsive assembly and disassembly as well as dynamic volume and shape changes. The purpose of this review is to describe recent progress in design and development of bioinspired dynamic materials, with a particular emphasis on hydrogel networks. We specifically focus on emerging approaches that use biological phenomena as an inspiration for design of materials.
A microfluidic islet perifusion device was developed for the assessment of dynamic insulin secretion of multiple pancreatic islets and simultaneous fluorescence imaging of calcium influx and mitochondrial potential changes. The fanned out design of the second generation device optimized the efficient mixing and uniform distribution of rapid alternating solutions in the perifusion chamber and allowed for the generation of reproducible glucose gradients. Simultaneous imaging of calcium influx and mitochondrial potential changes in response to glucose stimulation showed high signal-noise ratio and spatial-temporal resolution. These results suggest that this system can be used for detailed study of the endocrine function of pancreatic islets with simultaneous imaging of intracellular ion fluxes and mitochondrial membrane potential changes. This tool can be used for quality assessment of islets preparation before transplantation and for in vitro studies of islet function.
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