@article{reynolds_wilkins_martin_taggart_rivera_tunc-ozdemir_rufty_lobaton_bozkurt_daniele_2024, title={Evaluating Bacterial Nanocellulose Interfaces for Recording Surface Biopotentials from Plants}, volume={24}, ISSN={["1424-8220"]}, url={https://doi.org/10.3390/s24072335}, DOI={10.3390/s24072335}, abstractNote={The study of plant electrophysiology offers promising techniques to track plant health and stress in vivo for both agricultural and environmental monitoring applications. Use of superficial electrodes on the plant body to record surface potentials may provide new phenotyping insights. Bacterial nanocellulose (BNC) is a flexible, optically translucent, and water-vapor-permeable material with low manufacturing costs, making it an ideal substrate for non-invasive and non-destructive plant electrodes. This work presents BNC electrodes with screen-printed carbon (graphite) ink-based conductive traces and pads. It investigates the potential of these electrodes for plant surface electrophysiology measurements in comparison to commercially available standard wet gel and needle electrodes. The electrochemically active surface area and impedance of the BNC electrodes varied based on the annealing temperature and time over the ranges of 50 °C to 90 °C and 5 to 60 min, respectively. The water vapor transfer rate and optical transmittance of the BNC substrate were measured to estimate the level of occlusion caused by these surface electrodes on the plant tissue. The total reduction in chlorophyll content under the electrodes was measured after the electrodes were placed on maize leaves for up to 300 h, showing that the BNC caused only a 16% reduction. Maize leaf transpiration was reduced by only 20% under the BNC electrodes after 72 h compared to a 60% reduction under wet gel electrodes in 48 h. On three different model plants, BNC–carbon ink surface electrodes and standard invasive needle electrodes were shown to have a comparable signal quality, with a correlation coefficient of >0.9, when measuring surface biopotentials induced by acute environmental stressors. These are strong indications of the superior performance of the BNC substrate with screen-printed graphite ink as an electrode material for plant surface biopotential recordings.}, number={7}, journal={SENSORS}, author={Reynolds, James and Wilkins, Michael and Martin, Devon and Taggart, Matthew and Rivera, Kristina R. and Tunc-Ozdemir, Meral and Rufty, Thomas and Lobaton, Edgar and Bozkurt, Alper and Daniele, Michael A.}, year={2024}, month={Apr} }
 @article{rivera_bilton_burclaff_czerwinski_liu_trueblood_hinesley_breau_deal_joshi_et al._2023, title={Hypoxia Primes Human ISCs for Interleukin-Dependent Rescue of Stem Cell Activity}, volume={16}, ISSN={["2352-345X"]}, DOI={10.1016/j.jcmgh.2023.07.012}, abstractNote={Background and AimsHypoxia in the intestinal epithelium can be caused by acute ischemic events or chronic inflammation in which immune cell infiltration produces inflammatory hypoxia starving the mucosa of oxygen. The epithelium has the capacity to regenerate after some ischemic and inflammatory conditions suggesting that intestinal stem cells (ISCs) are highly tolerant to acute and chronic hypoxia; however, the impact of hypoxia on human ISC (hISC) function has not been reported. Here we present a new microphysiological system (MPS) to investigate how hypoxia affects hISCs from healthy donors and test the hypothesis that prolonged hypoxia modulates how hISCs respond to inflammation-associated interleukins (ILs).MethodshISCs were exposed to <1.0% oxygen in the MPS for 6, 24, 48, and 72 hours. Viability, hypoxia-inducible factor 1a (HIF1a) response, transcriptomics, cell cycle dynamics, and response to cytokines were evaluated in hISCs under hypoxia. HIF stabilizers and inhibitors were screened to evaluate HIF-dependent responses.ResultsThe MPS enables precise, real-time control and monitoring of oxygen levels at the cell surface. Under hypoxia, hISCs maintain viability until 72 hours and exhibit peak HIF1a at 24 hours. hISC activity was reduced at 24 hours but recovered at 48 hours. Hypoxia induced increases in the proportion of hISCs in G1 and expression changes in 16 IL receptors. Prolyl hydroxylase inhibition failed to reproduce hypoxia-dependent IL-receptor expression patterns. hISC activity increased when treated IL1β, IL2, IL4, IL6, IL10, IL13, and IL25 and rescued hISC activity caused by 24 hours of hypoxia.ConclusionsHypoxia pushes hISCs into a dormant but reversible proliferative state and primes hISCs to respond to a subset of ILs that preserves hISC activity. These findings have important implications for understanding intestinal epithelial regeneration mechanisms caused by inflammatory hypoxia. Hypoxia in the intestinal epithelium can be caused by acute ischemic events or chronic inflammation in which immune cell infiltration produces inflammatory hypoxia starving the mucosa of oxygen. The epithelium has the capacity to regenerate after some ischemic and inflammatory conditions suggesting that intestinal stem cells (ISCs) are highly tolerant to acute and chronic hypoxia; however, the impact of hypoxia on human ISC (hISC) function has not been reported. Here we present a new microphysiological system (MPS) to investigate how hypoxia affects hISCs from healthy donors and test the hypothesis that prolonged hypoxia modulates how hISCs respond to inflammation-associated interleukins (ILs). hISCs were exposed to <1.0% oxygen in the MPS for 6, 24, 48, and 72 hours. Viability, hypoxia-inducible factor 1a (HIF1a) response, transcriptomics, cell cycle dynamics, and response to cytokines were evaluated in hISCs under hypoxia. HIF stabilizers and inhibitors were screened to evaluate HIF-dependent responses. The MPS enables precise, real-time control and monitoring of oxygen levels at the cell surface. Under hypoxia, hISCs maintain viability until 72 hours and exhibit peak HIF1a at 24 hours. hISC activity was reduced at 24 hours but recovered at 48 hours. Hypoxia induced increases in the proportion of hISCs in G1 and expression changes in 16 IL receptors. Prolyl hydroxylase inhibition failed to reproduce hypoxia-dependent IL-receptor expression patterns. hISC activity increased when treated IL1β, IL2, IL4, IL6, IL10, IL13, and IL25 and rescued hISC activity caused by 24 hours of hypoxia. Hypoxia pushes hISCs into a dormant but reversible proliferative state and primes hISCs to respond to a subset of ILs that preserves hISC activity. These findings have important implications for understanding intestinal epithelial regeneration mechanisms caused by inflammatory hypoxia.}, number={5}, journal={CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY}, author={Rivera, Kristina R. and Bilton, R. Jarrett and Burclaff, Joseph and Czerwinski, Michael J. and Liu, Jintong and Trueblood, Jessica M. and Hinesley, Caroline M. and Breau, Keith A. and Deal, Halston E. and Joshi, Shlok and et al.}, year={2023}, pages={823–846} }
 @article{pozdin_erb_downey_rivera_daniele_2021, title={Monitoring of random microvessel network formation by in-line sensing of flow rates: A numerical and in vitro investigation}, volume={331}, ISSN={["1873-3069"]}, DOI={10.1016/j.sna.2021.112970}, abstractNote={The directed or de novo formation of microvasculature in engineered tissue constructs is essential for accurately replicating physiological function. A limiting factor of a system relying on spontaneous microvessel formation is the inability to precisely quantify the development of the microvascular network and control fluid moving through formed vessels. Herein, we report a strategy to monitor the dynamic formation of microscale fluid networks, which can be translated to the monitoring of microvasculature development in engineered tissue constructs. The non-invasive, non-destructive monitoring and characterization of the fluid network is achieved via in-line sensing of fluid flow rate and correlating this measurement to the hydrodynamic resistance of the fluid network to model the progression of microvessel formation and connectivity. Computational fluid dynamics, equivalent circuit, and experimental models were compared, which simulated multi-generational branching or splitting microvessel networks. The networks simulated vessels with varying cross-sectional area, up to 16 branching vessels, and microvessel network volume ranging from ˜20−30 mm3. In all models, the increasing degree of network complexity and volume corresponded to a decrease in jumper flow-rate measured; however, vessel cross-section also impacted the measured jumper flow rate, i.e. at low vessel height (<200 μm) response was dominated by increased network volume and at higher vessel height (>200 μm) the response was dominated by resistance of narrow channels. An approximately 2% error was exhibited between the models, which was attributed to variation in the geometry of the fabricated models and illustrates the potential to precisely and non-destructively monitor microvessel network development and volumetric changes.}, journal={SENSORS AND ACTUATORS A-PHYSICAL}, author={Pozdin, Vladimir A. and Erb, Patrick D. and Downey, McKenna and Rivera, Kristina R. and Daniele, Michael}, year={2021}, month={Nov} }
 @article{zwarycz_gracz_rivera_williamson_samsa_starmer_daniele_salter-cid_zhao_magness_2019, title={IL22 Inhibits Epithelial Stem Cell Expansion in an Ileal Organoid Model}, volume={7}, ISSN={["2352-345X"]}, DOI={10.1016/j.jcmgh.2018.06.008}, abstractNote={Crohn's disease is an inflammatory bowel disease that affects the ileum and is associated with increased cytokines. Although interleukin (IL)6, IL17, IL21, and IL22 are increased in Crohn's disease and are associated with disrupted epithelial regeneration, little is known about their effects on the intestinal stem cells (ISCs) that mediate tissue repair. We hypothesized that ILs may target ISCs and reduce ISC-driven epithelial renewal.A screen of IL6, IL17, IL21, or IL22 was performed on ileal mouse organoids. Computational modeling was used to predict microenvironment cytokine concentrations. Organoid size, survival, proliferation, and differentiation were characterized by morphometrics, quantitative reverse-transcription polymerase chain reaction, and immunostaining on whole organoids or isolated ISCs. ISC function was assayed using serial passaging to single cells followed by organoid quantification. Single-cell RNA sequencing was used to assess Il22ra1 expression patterns in ISCs and transit-amplifying (TA) progenitors. An IL22-transgenic mouse was used to confirm the impact of increased IL22 on proliferative cells in vivo.High IL22 levels caused decreased ileal organoid survival, however, resistant organoids grew larger and showed increased proliferation over controls. Il22ra1 was expressed on only a subset of ISCs and TA progenitors. IL22-treated ISCs did not show appreciable differentiation defects, but ISC biomarker expression and self-renewal-associated pathway activity was reduced and accompanied by an inhibition of ISC expansion. In vivo, chronically increased IL22 levels, similar to predicted microenvironment levels, showed increases in proliferative cells in the TA zone with no increase in ISCs.Increased IL22 limits ISC expansion in favor of increased TA progenitor cell expansion.}, number={1}, journal={CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY}, author={Zwarycz, Bailey and Gracz, Adam D. and Rivera, Kristina R. and Williamson, Ian A. and Samsa, Leigh A. and Starmer, Josh and Daniele, Michael A. and Salter-Cid, Luisa and Zhao, Qihong and Magness, Scott T.}, year={2019}, pages={1–17} }
 @article{rivera_pozdin_young_erb_wisniewski_magness_daniele_2019, title={Integrated phosphorescence-based photonic biosensor (iPOB) for monitoring oxygen levels in 3D cell culture systems}, volume={123}, ISSN={["1873-4235"]}, DOI={10.1016/j.bios.2018.07.035}, abstractNote={Physiological processes, such as respiration, circulation, digestion, and many pathologies alter oxygen concentration in the blood and tissue. When designing culture systems to recapitulate the in vivo oxygen environment, it is important to integrate systems for monitoring and controlling oxygen concentration. Herein, we report the design and engineering of a system to remotely monitor and control oxygen concentration inside a device for 3D cell culture. We integrate a photonic oxygen biosensor into the 3D tissue scaffold and regulate oxygen concentration via the control of purging gas flow. The integrated phosphorescence-based oxygen biosensor employs the quenching of palladium-benzoporphyrin by molecular oxygen to transduce the local oxygen concentration in the 3D tissue scaffold. The system is validated by testing the effects of normoxic and hypoxic culture conditions on healthy and tumorigenic breast epithelial cells, MCF-10A cells and BT474 cells, respectively. Under hypoxic conditions, both cell types exhibited upregulation of downstream target genes for the hypoxia marker gene, hypoxia-inducible factor 1α (HIF1A). Lastly, by monitoring the real-time fluctuation of oxygen concentration, we illustrated the formation of hypoxic culture conditions due to limited diffusion of oxygen through 3D tissue scaffolds.}, journal={BIOSENSORS & BIOELECTRONICS}, author={Rivera, Kristina R. and Pozdin, Vladimir A. and Young, Ashlyn T. and Erb, Patrick D. and Wisniewski, Natalie A. and Magness, Scott T. and Daniele, Michael}, year={2019}, month={Jan}, pages={131–140} }
 @misc{rivera_yokus_erb_pozdin_daniele_2019, title={Measuring and regulating oxygen levels in microphysiological systems: design, material, and sensor considerations}, volume={144}, ISSN={["1364-5528"]}, DOI={10.1039/c8an02201a}, abstractNote={Quantifying and regulating oxygen in a microphysiological models can be achievedviaan array of technologies, and is an essential component of recapitulating tissue-specific microenvironments.}, number={10}, journal={ANALYST}, author={Rivera, Kristina R. and Yokus, Murat A. and Erb, Patrick D. and Pozdin, Vladimir A. and Daniele, Michael}, year={2019}, month={May}, pages={3190–3215} }
 @misc{young_rivera_erb_daniele_2019, title={Monitoring of Microphysiological Systems: Integrating Sensors and Real-Time Data Analysis toward Autonomous Decision-Making}, volume={4}, ISSN={["2379-3694"]}, DOI={10.1021/acssensors.8b01549}, abstractNote={Microphysiological systems replicate human organ function and are promising technologies for discovery of translatable biomarkers, pharmaceuticals, and regenerative therapies. Because microphysiological systems require complex microscale anatomical structures and heterogeneous cell populations, a major challenge remains to manufacture and operate these products with reproducible and standardized function. In this Perspective, three stages of microphysiological system monitoring, including process, development, and function, are assessed. The unique features and remaining technical challenges for the required sensors are discussed. Monitoring of microphysiological systems requires nondestructive, continuous biosensors and imaging techniques. With such tools, the extent of cellular and tissue development, as well as function, can be autonomously determined and optimized by correlating physical and chemical sensor outputs with markers of physiological performance. Ultimately, data fusion and analyses across process, development, and function monitors can be implemented to adopt microphysiological systems for broad research and commercial applications.}, number={6}, journal={ACS SENSORS}, author={Young, Ashlyn T. and Rivera, Kristina R. and Erb, Patrick D. and Daniele, Michael A.}, year={2019}, month={Jun}, pages={1454–1464} }