I received my PhD degree in Mechanical Engineering with a focus on Bioengineering from the Sharif University of Technology, Tehran, Iran in 2021. My Ph.D. thesis was about the design, fabrication of microfluidic devices for separating circulating tumor cells from blood. During my Ph.D., I joined Prof. Ali Khademhossini's Lab at the University of California, Los Angeles and Terasaki Institute for Biomedical innovation for two years as a visiting researcher. Following my PhD, I joined Prof. Anna Herland’s lab at KTH Royal Institute of Technology as a postdoctoral researcher from Sep. 2021 for two years. In Herland’s lab my research focused on the investigation of the brain energy metabolism using a Brain-on-a-chip model integrated with metabolic biosensors.
Currently, I am working as a postdoctoral researcher at Prof. Pratx's lab in Radiation Oncology Department at Stanford University. My current research focuses on developing an advanced Tumor-on-a-chip model for drug screening applications.
Postdoc, KTH Royal of Technology, Biomedical Engineering (2023)
PhD, Sharif University of Technology, Mechanical Engineering (Bioengineering) (2021)
Visting Researcher, University of California, Los Angeles (UCLA), Bioengineering (2020)
MSc, Sharif University of Technology, Mechanical Engineering (2014)
BSc, University of Tehran, Mechanical Engineering (2012)
Guillem Pratx, Postdoctoral Faculty Sponsor
Rapid integration of screen-printed electrodes into thermoplastic organ-on-a-chip devices for real-time monitoring of trans-endothelial electrical resistance.
2023; 25 (4): 37
Trans-endothelial electrical resistance (TEER) is one of the most widely used indicators to quantify the barrier integrity of endothelial layers. Over the last decade, the integration of TEER sensors into organ-on-a-chip (OOC) platforms has gained increasing interest for its efficient and effective measurement of TEER in OOCs. To date, microfabricated electrodes or direct insertion of wires has been used to integrate TEER sensors into OOCs, with each method having advantages and disadvantages. In this study, we developed a TEER-SPE chip consisting of carbon-based screen-printed electrodes (SPEs) embedded in a poly(methyl methacrylate) (PMMA)-based multi-layered microfluidic device with a porous poly(ethylene terephthalate) membrane in-between. As proof of concept, we demonstrated the successful cultures of hCMEC/D3 cells and the formation of confluent monolayers in the TEER-SPE chip and obtained TEER measurements for 4 days. Additionally, the TEER-SPE chip could detect changes in the barrier integrity due to shear stress or an inflammatory cytokine (i.e., tumor necrosis factor-α). The novel approach enables a low-cost and facile fabrication of carbon-based SPEs on PMMA substrates and the subsequent assembly of PMMA layers for rapid prototyping. Being cost-effective and cleanroom-free, our method lowers the existing logistical and technical barriers presenting itself as another step forward to the broader adoption of OOCs with TEER measurement capability.
View details for DOI 10.1007/s10544-023-00669-9
View details for PubMedID 37740819
Enhanced Maturation of 3D Bioprinted Skeletal Muscle Tissue Constructs Encapsulating Soluble Factor-Releasing Microparticles
Several microfabrication technologies have been used to engineer native-like skeletal muscle tissues. However, the successful development of muscle remains a significant challenge in the tissue engineering field. Muscle tissue engineering aims to combine muscle precursor cells aligned within a highly organized 3D structure and biological factors crucial to support cell differentiation and maturation into functional myotubes and myofibers. In this study, the use of 3D bioprinting is proposed for the fabrication of muscle tissues using gelatin methacryloyl (GelMA) incorporating sustained insulin-like growth factor-1 (IGF-1)-releasing microparticles and myoblast cells. This study hypothesizes that functional and mature myotubes will be obtained more efficiently using a bioink that can release IGF-1 sustainably for in vitro muscle engineering. Synthesized microfluidic-assisted polymeric microparticles demonstrate successful adsorption of IGF-1 and sustained release of IGF-1 at physiological pH for at least 21 days. Incorporating the IGF-1-releasing microparticles in the GelMA bioink assisted in promoting the alignment of myoblasts and differentiation into myotubes. Furthermore, the myotubes show spontaneous contraction in the muscle constructs bioprinted with IGF-1-releasing bioink. The proposed bioprinting strategy aims to improve the development of new therapies applied to the regeneration and maturation of muscle tissues.
View details for DOI 10.1002/mabi.202300276
View details for Web of Science ID 001050996500001
View details for PubMedID 37534566
Aerogel-Based Biomaterials for Biomedical Applications: From Fabrication Methods to Disease-Targeting Applications
Aerogel-based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol-gel, aging, drying, and self-assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic-based technologies and 3D printing can be combined with aerogel-based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel-based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels.
View details for DOI 10.1002/advs.202204681
View details for Web of Science ID 000992292300001
View details for PubMedID 37217831
View details for PubMedCentralID PMC10427407
- Modelling Brain in a Chip JOURNAL OF CRANIOFACIAL SURGERY 2023; 34 (3): 845-847
- Micromechanical property mismatch between pericellular and extracellular matrices regulates stem cell articular and hypertrophic chondrogenesis MATTER 2023; 6 (2)
Magnetically Driven Manipulation of Nonmagnetic Liquid Marbles: Billiards with Liquid Marbles
2023; 14 (1)
Liquid marbles are droplets encapsulated by a layer of hydrophobic nanoparticles and have been extensively employed in digital microfluidics and lab-on-a-chip systems in recent years. In this study, magnetic liquid marbles were used to manipulate nonmagnetic liquid marbles. To achieve this purpose, a ferrofluid liquid marble (FLM) was employed and attracted toward an electromagnet, resulting in an impulse to a water liquid marble (WLM) on its way to the electromagnet. It was observed that the manipulation of the WLM by the FLM was similar to the collision of billiard balls except that the liquid marbles exhibited an inelastic collision. Taking the FLM as the projectile ball and the WLM as the other target balls, one can adjust the displacement and direction of the WLM precisely, similar to an expert billiard player. Firstly, the WLM displacement can be adjusted by altering the liquid marble volumes, the initial distances from the electromagnet, and the coil current. Secondly, the WLM direction can be adjusted by changing the position of the WLM relative to the connecting line between the FLM center and the electromagnet. Results show that when the FLM or WLM volume increases by five times, the WLM shooting distance approximately increases by 200% and decreases by 75%, respectively.
View details for DOI 10.3390/mi14010049
View details for Web of Science ID 000918593700001
View details for PubMedID 36677108
View details for PubMedCentralID PMC9865651
A Microfluidic Contact Lens to Address Contact Lens-Induced Dry Eye
2023; 19 (11): e2207017
The contact lens (CL) industry has made great strides in improving CL-wearing experiences. However, a large amount of CL wearers continue to experience ocular dryness, known as contact lens-induced dry eye (CLIDE), stemming from the reduction in tear volume, tear film instability, increased tear osmolarity followed by inflammation and resulting in ocular discomfort and visual disturbances. In this article, to address tear film thinning between the CL and the ocular surface, the concept of using a CL with microchannels to deliver the tears from the pre-lens tear film (PrLTF) to the post-lens ocular surface using in vitro eye-blink motion is investigated. This study reports an eye-blink mimicking system with microfluidic poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogel with integrated microchannels to demonstrate eye-blink assisted flow through microchannels. This in vitro experimental study provides a proof-of-concept result that tear transport from PrLTF to post-lens tear film can be enhanced by an artificial eyelid motion in a pressure range of 0.1-5 kPa (similar to human eyelid pressure) through poly(HEMA) microchannels. Simulation is conducted to support the hypothesis. This work demonstrates the feasibility of developing microfluidic CLs with the potential to help prevent or minimize CLIDE and discomfort by the enhanced transport of pre-lens tears to the post-lens ocular surface.
View details for DOI 10.1002/smll.202207017
View details for Web of Science ID 000903646800001
View details for PubMedID 36564357
The Effect of Non-Uniform Magnetic Field on the Efficiency of Mixing in Droplet-Based Microfluidics: A Numerical Investigation
2022; 13 (10)
Achieving high efficiency and throughput in droplet-based mixing over a small characteristic length, such as microfluidic channels, is one of the crucial parameters in Lab-on-a-Chip (LOC) applications. One solution to achieve efficient mixing is to use active mixers in which an external power source is utilized to mix two fluids. One of these active methods is magnetic micromixers using ferrofluid. In this technique, magnetic nanoparticles are used to make one phase responsive to magnetic force, and then by applying a magnetic field, two fluid phases, one of which is magneto-responsive, will sufficiently mix. In this study, we investigated the effect of the magnetic field's characteristics on the efficiency of the mixing process inside droplets. When different concentrations of ferrofluids are affected by a constant magnetic field, there is no significant change in mixing efficiency. As the magnetic field intensifies, the magnetic force makes the circulation flow inside the droplet asymmetric, leading to chaotic advection, which creates a flow that increases the mixing efficiency. The results show that the use of magnetic fields is an effective method to enhance the mixing efficiency within droplets, and the efficiency of mixing increases from 65.4 to 86.1% by increasing the magnetic field intensity from 0 to 90 mT. Besides that, the effect of ferrofluid's concentration on the mixing efficiency is studied. It is shown that when the concentration of the ferrofluid changes from 0 to 0.6 mol/m3, the mixing efficiency increases considerably. It is also shown that by changing the intensity of the magnetic field, the mixing efficiency increases by about 11%.
View details for DOI 10.3390/mi13101661
View details for Web of Science ID 000873210300001
View details for PubMedID 36296014
View details for PubMedCentralID PMC9608787
Metabolic Assessment of Human Induced Pluripotent Stem Cells-Derived Astrocytes and Fetal Primary Astrocytes: Lactate and Glucose Turnover
2022; 12 (10)
Astrocytes represent one of the main cell types in the brain and play a crucial role in brain functions, including supplying the energy demand for neurons. Moreover, they are important regulators of metabolite levels. Glucose uptake and lactate production are some of the main observable metabolic actions of astrocytes. To gain insight into these processes, it is essential to establish scalable and functional sources for in vitro studies of astrocytes. In this study, we compared the metabolic turnover of glucose and lactate in astrocytes derived from human induced pluripotent stem cell (hiPSC)-derived Astrocytes (hiAstrocytes) as a scalable astrocyte source to human fetal astrocytes (HFAs). Using a user-friendly, commercial flow-based biosensor, we could verify that hiAstrocytes are as glycogenic as their fetal counterparts, but their normalized metabolic turnover is lower. Specifically, under identical culture conditions in a defined media, HFAs have 2.3 times higher levels of lactate production compared to hiAstrocytes. In terms of glucose, HFAs have 2.1 times higher consumption levels than hiAstrocytes at 24 h. Still, as we describe their glycogenic phenotype, our study demonstrates the use of hiAstrocytes and flow-based biosensors for metabolic studies of astrocyte function.
View details for DOI 10.3390/bios12100839
View details for Web of Science ID 000874174100001
View details for PubMedID 36290976
View details for PubMedCentralID PMC9599592
Brain-on-a-chip: Recent advances in design and techniques for microfluidic models of the brain in health and disease
2022; 285: 121531
Recent advances in biomaterials, microfabrication, microfluidics, and cell biology have led to the development of organ-on-a-chip devices that can reproduce key functions of various organs. Such platforms promise to provide novel insights into various physiological events, including mechanisms of disease, and evaluate the effects of external interventions, such as drug administration. The neuroscience field is expected to benefit greatly from these innovative tools. Conventional ex vivo studies of the nervous system have been limited by the inability of cell culture to adequately mimic in vivo physiology. While animal models can be used, their relevance to human physiology is uncertain and their use is laborious and associated with ethical issues. To date, organ-on-a-chip systems have been developed to model different tissue components of the brain, including brain regions with specific functions and the blood brain barrier, both in normal and pathophysiological conditions. While the field is still in its infancy, it is expected to have major impact on studies of neurophysiology, pathology and neuropharmacology in future. Here, we review advances made and limitations faced in an effort to stimulate development of the next generation of brain-on-a-chip devices.
View details for DOI 10.1016/j.biomaterials.2022.121531
View details for Web of Science ID 000799391800002
View details for PubMedID 35533441
Droplet-based microfluidics in biomedical applications
2022; 14 (2)
Droplet-based microfluidic systems have been employed to manipulate discrete fluid volumes with immiscible phases. Creating the fluid droplets at microscale has led to a paradigm shift in mixing, sorting, encapsulation, sensing, and designing high throughput devices for biomedical applications. Droplet microfluidics has opened many opportunities in microparticle synthesis, molecular detection, diagnostics, drug delivery, and cell biology. In the present review, we first introduce standard methods for droplet generation (i.e. passive and active methods) and discuss the latest examples of emulsification and particle synthesis approaches enabled by microfluidic platforms. Then, the applications of droplet-based microfluidics in different biomedical applications are detailed. Finally, a general overview of the latest trends along with the perspectives and future potentials in the field are provided.
View details for DOI 10.1088/1758-5090/ac39a9
View details for Web of Science ID 000746161500001
View details for PubMedID 34781274
Additively manufactured metallic biomaterials
2022; 15: 214-249
Metal additive manufacturing (AM) has led to an evolution in the design and fabrication of hard tissue substitutes, enabling personalized implants to address each patient's specific needs. In addition, internal pore architectures integrated within additively manufactured scaffolds, have provided an opportunity to further develop and engineer functional implants for better tissue integration, and long-term durability. In this review, the latest advances in different aspects of the design and manufacturing of additively manufactured metallic biomaterials are highlighted. After introducing metal AM processes, biocompatible metals adapted for integration with AM machines are presented. Then, we elaborate on the tools and approaches undertaken for the design of porous scaffold with engineered internal architecture including, topology optimization techniques, as well as unit cell patterns based on lattice networks, and triply periodic minimal surface. Here, the new possibilities brought by the functionally gradient porous structures to meet the conflicting scaffold design requirements are thoroughly discussed. Subsequently, the design constraints and physical characteristics of the additively manufactured constructs are reviewed in terms of input parameters such as design features and AM processing parameters. We assess the proposed applications of additively manufactured implants for regeneration of different tissue types and the efforts made towards their clinical translation. Finally, we conclude the review with the emerging directions and perspectives for further development of AM in the medical industry.
View details for DOI 10.1016/j.bioactmat.2021.12.027
View details for Web of Science ID 000789696200001
View details for PubMedID 35386359
View details for PubMedCentralID PMC8941217
Advanced Materials and Sensors for Microphysiological Systems: Focus on Electronic and Electrooptical Interfaces
2022; 34 (17): e2107876
Advanced in vitro cell culture systems or microphysiological systems (MPSs), including microfluidic organ-on-a-chip (OoC), are breakthrough technologies in biomedicine. These systems recapitulate features of human tissues outside of the body. They are increasingly being used to study the functionality of different organs for applications such as drug evolutions, disease modeling, and precision medicine. Currently, developers and endpoint users of these in vitro models promote how they can replace animal models or even be a better ethically neutral and humanized alternative to study pathology, physiology, and pharmacology. Although reported models show a remarkable physiological structure and function compared to the conventional 2D cell culture, they are almost exclusively based on standard passive polymers or glass with none or minimal real-time stimuli and readout capacity. The next technology leap in reproducing in vivo-like functionality and real-time monitoring of tissue function could be realized with advanced functional materials and devices. This review describes the currently reported electronic and optical advanced materials for sensing and stimulation of MPS models. In addition, an overview of multi-sensing for Body-on-Chip platforms is given. Finally, one gives the perspective on how advanced functional materials could be integrated into in vitro systems to precisely mimic human physiology.
View details for DOI 10.1002/adma.202107876
View details for Web of Science ID 000768329700001
View details for PubMedID 34913206
- Design of two Inertial-based microfluidic devices for cancer cell separation from Blood: A serpentine inertial device and an integrated inertial and magnetophoretic device CHEMICAL ENGINEERING SCIENCE 2022; 252
Assessing the aneurysm occlusion efficacy of a shear-thinning biomaterial in a 3D-printed model.
Journal of the mechanical behavior of biomedical materials
2022; 130: 105156
Metallic coil embolization is a common method for the endovascular treatment of visceral artery aneurysms (VAA) and visceral artery pseudoaneurysms (VAPA); however, this treatment is suboptimal due to the high cost of coils, incomplete volume occlusion, poor reendothelialization, aneurysm puncture, and coil migration. Several alternative treatment strategies are available, including stent flow diverters, glue embolics, gelfoam slurries, and vascular mesh plugs-each of which have their own disadvantages. Here, we investigated the in vitro capability of a shear-thinning biomaterial (STB), a nanocomposite hydrogel composed of gelatin and silicate nanoplatelets, for the minimally-invasive occlusion of simple necked aneurysm models. We demonstrated the injectability of STB through various clinical catheters, engineered an in vitro testing apparatus to independently manipulate aneurysm neck diameter, fluid flow rate, and flow waveform, and tested the stability of STB within the models under various conditions. Our experiments show that STB is able to withstand at least 1.89Pa of wall shear stress, as estimated by computational fluid dynamics. STB is also able to withstand up to 10mLs-1 pulsatile flow with a waveform mimicking blood flow in the human femoral artery and tolerate greater pressure changes than those in the human aorta. We ultimately found that our in vitro system was limited by supraphysiologic pressure changes caused by aneurysm models with low compliance.
View details for DOI 10.1016/j.jmbbm.2022.105156
View details for PubMedID 35397405
Three-dimensional transistor arrays for intra- and inter-cellular recording
2022; 17 (3): 292-+
Electrical impulse generation and its conduction within cells or cellular networks are the cornerstone of electrophysiology. However, the advancement of the field is limited by sensing accuracy and the scalability of current recording technologies. Here we describe a scalable platform that enables accurate recording of transmembrane potentials in electrogenic cells. The platform employs a three-dimensional high-performance field-effect transistor array for minimally invasive cellular interfacing that produces faithful recordings, as validated by the gold standard patch clamp. Leveraging the high spatial and temporal resolutions of the field-effect transistors, we measured the intracellular signal conduction velocity of a cardiomyocyte to be 0.182 m s-1, which is about five times the intercellular velocity. We also demonstrate intracellular recordings in cardiac muscle tissue constructs and reveal the signal conduction paths. This platform could provide new capabilities in probing the electrical behaviours of single cells and cellular networks, which carries broad implications for understanding cellular physiology, pathology and cell-cell interactions.
View details for DOI 10.1038/s41565-021-01040-w
View details for Web of Science ID 000734148200004
View details for PubMedID 34949774
View details for PubMedCentralID PMC8994210
Recent developments in mussel-inspired materials for biomedical applications
2021; 9 (20): 6653-6672
Over the decades, researchers have strived to synthesize and modify nature-inspired biomaterials, with the primary aim to address the challenges of designing functional biomaterials for regenerative medicine and tissue engineering. Among these challenges, biocompatibility and cellular interactions have been extensively investigated. Some of the most desirable characteristics for biomaterials in these applications are the loading of bioactive molecules, strong adhesion to moist areas, improvement of cellular adhesion, and self-healing properties. Mussel-inspired biomaterials have received growing interest mainly due to the changes in mechanical and biological functions of the scaffold due to catechol modification. Here, we summarize the chemical and biological principles and the latest advancements in production, as well as the use of mussel-inspired biomaterials. Our main focus is the polydopamine coating, the conjugation of catechol with other polymers, and the biomedical applications that polydopamine moieties are used for, such as matrices for drug delivery, tissue regeneration, and hemostatic control. We also present a critical conclusion and an inspired view on the prospects for the development and application of mussel-inspired materials.
View details for DOI 10.1039/d1bm01126j
View details for Web of Science ID 000697792400001
View details for PubMedID 34550125
Design of a Hybrid Inertial and Magnetophoretic Microfluidic Device for CTCs Separation from Blood
2021; 12 (8)
Circulating tumor cells (CTCs) isolation from a blood sample plays an important role in cancer diagnosis and treatment. Microfluidics offers a great potential for cancer cell separation from the blood. Among the microfluidic-based methods for CTC separation, the inertial method as a passive method and magnetic method as an active method are two efficient well-established methods. Here, we investigated the combination of these two methods to separate CTCs from a blood sample in a single chip. Firstly, numerical simulations were performed to analyze the fluid flow within the proposed channel, and the particle trajectories within the inertial cell separation unit were investigated to determine/predict the particle trajectories within the inertial channel in the presence of fluid dynamic forces. Then, the designed device was fabricated using the soft-lithography technique. Later, the CTCs were conjugated with magnetic nanoparticles and Ep-CAM antibodies to improve the magnetic susceptibility of the cells in the presence of a magnetic field by using neodymium permanent magnets of 0.51 T. A diluted blood sample containing nanoparticle-conjugated CTCs was injected into the device at different flow rates to analyze its performance. It was found that the flow rate of 1000 µL/min resulted in the highest recovery rate and purity of ~95% and ~93% for CTCs, respectively.
View details for DOI 10.3390/mi12080877
View details for Web of Science ID 000690471300001
View details for PubMedID 34442499
View details for PubMedCentralID PMC8401779
Bioengineered Multicellular Liver Microtissues for Modeling Advanced Hepatic Fibrosis Driven Through Non-Alcoholic Fatty Liver Disease
2021; 17 (14): e2007425
Despite considerable efforts in modeling liver disease in vitro, it remains difficult to recapitulate the pathogenesis of the advanced phases of non-alcoholic fatty liver disease (NAFLD) with inflammation and fibrosis. Here, a liver-on-a-chip platform with bioengineered multicellular liver microtissues is developed, composed of four major types of liver cells (hepatocytes, endothelial cells, Kupffer cells, and stellate cells) to implement a human hepatic fibrosis model driven by NAFLD: i) lipid accumulation in hepatocytes (steatosis), ii) neovascularization by endothelial cells, iii) inflammation by activated Kupffer cells (steatohepatitis), and iv) extracellular matrix deposition by activated stellate cells (fibrosis). In this model, the presence of stellate cells in the liver-on-a-chip model with fat supplementation showed elevated inflammatory responses and fibrosis marker up-regulation. Compared to transforming growth factor-beta-induced hepatic fibrosis models, this model includes the native pathological and chronological steps of NAFLD which shows i) higher fibrotic phenotypes, ii) increased expression of fibrosis markers, and iii) efficient drug transport and metabolism. Taken together, the proposed platform will enable a better understanding of the mechanisms underlying fibrosis progression in NAFLD as well as the identification of new drugs for the different stages of NAFLD.
View details for DOI 10.1002/smll.202007425
View details for Web of Science ID 000626644800001
View details for PubMedID 33690979
View details for PubMedCentralID PMC8035291
Healthy and diseased in vitro models of vascular systems
LAB ON A CHIP
2021; 21 (4): 641-659
Irregular hemodynamics affects the progression of various vascular diseases, such atherosclerosis or aneurysms. Despite the extensive hemodynamics studies on animal models, the inter-species differences between humans and animals hamper the translation of such findings. Recent advances in vascular tissue engineering and the suitability of in vitro models for interim analysis have increased the use of in vitro human vascular tissue models. Although the effect of flow on endothelial cell (EC) pathophysiology and EC-flow interactions have been vastly studied in two-dimensional systems, they cannot be used to understand the effect of other micro- and macro-environmental parameters associated with vessel wall diseases. To generate an ideal in vitro model of the vascular system, essential criteria should be included: 1) the presence of smooth muscle cells or perivascular cells underneath an EC monolayer, 2) an elastic mechanical response of tissue to pulsatile flow pressure, 3) flow conditions that accurately mimic the hemodynamics of diseases, and 4) geometrical features required for pathophysiological flow. In this paper, we review currently available in vitro models that include flow dynamics and discuss studies that have tried to address the criteria mentioned above. Finally, we critically review in vitro fluidic models of atherosclerosis, aneurysm, and thrombosis.
View details for DOI 10.1039/d0lc00464b
View details for Web of Science ID 000620729800002
View details for PubMedID 33507199
Microengineered poly(HEMA) hydrogels for wearable contact lens biosensing
LAB ON A CHIP
2020; 20 (22): 4205-4214
Microchannels in hydrogels play an essential role in enabling a smart contact lens. However, microchannels have rarely been created in commercial hydrogel contact lenses due to their sensitivity to conventional microfabrication techniques. Here, we report the fabrication of microchannels in poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogels that are used in commercial contact lenses with a three-dimensional (3D) printed mold. We investigated the corresponding capillary flow behaviors in these microchannels. We observed different capillary flow regimes in these microchannels, depending on their hydration level. In particular, we found that a peristaltic pressure could reinstate flow in a dehydrated channel, indicating that the motion of eye-blinking may help tears flow in a microchannel-containing contact lens. Colorimetric pH and electrochemical Na+ sensing capabilities were demonstrated in these microchannels. This work paves the way for the development of microengineered poly(HEMA) hydrogels for various biomedical applications such as eye-care and wearable biosensing.
View details for DOI 10.1039/d0lc00446d
View details for Web of Science ID 000588192800007
View details for PubMedID 33048069
Gut-on-a-chip: Current progress and future opportunities
2020; 255: 120196
Organ-on-a-chip technology tries to mimic the complexity of native tissues in vitro. Important progress has recently been made in using this technology to study the gut with and without microbiota. These in vitro models can serve as an alternative to animal models for studying physiology, pathology, and pharmacology. While these models have greater physiological relevance than two-dimensional (2D) cell systems in vitro, endocrine and immunological functions in gut-on-a-chip models are still poorly represented. Furthermore, the construction of complex models, in which different cell types and structures interact, remains a challenge. Generally, gut-on-a-chip models have the potential to advance our understanding of the basic interactions found within the gut and lay the foundation for future applications in understanding pathophysiology, developing drugs, and personalizing medical treatments.
View details for DOI 10.1016/j.biomaterials.2020.120196
View details for Web of Science ID 000555693800035
View details for PubMedID 32623181
View details for PubMedCentralID PMC7396314
Combined Effects of Electric Stimulation and Microgrooves in Cardiac Tissue-on-a-Chip for Drug Screening
2020; 4 (10)
Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart-on-a-chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well-aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip is made with facile lithographic and laser-cutting processes that can be easily scaled up to high-throughput format. The maturation and phenotypic changes of CMs cultured on the heart-on-a-chip is validated and it can be treated with various drugs to evaluate cardiotoxicity and cardioprotective efficacy. The heart-on-a-chip can provide a high-throughput drug screening platform in preclinical drug development.
View details for DOI 10.1002/smtd.202000438
View details for Web of Science ID 000569327600001
View details for PubMedID 34423115
View details for PubMedCentralID PMC8372829
Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury
2020; 182 (3): 545-+
Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces expression of mechanosensitive integrins that drive fibroblast activation and increase scar size. Cilengitide, an inhibitor of specific integrins, rescues the phenotype of increased post-injury scarring in collagen-V-deficient mice. These observations demonstrate that collagen V regulates scar size in an integrin-dependent manner.
View details for DOI 10.1016/j.cell.2020.06.030
View details for Web of Science ID 000558649000005
View details for PubMedID 32621799
View details for PubMedCentralID PMC7415659
Design and Simulation of an Integrated Centrifugal Microfluidic Device for CTCs Separation and Cell Lysis
2020; 11 (7)
Separation of circulating tumor cells (CTCs) from blood samples and subsequent DNA extraction from these cells play a crucial role in cancer research and drug discovery. Microfluidics is a versatile technology that has been applied to create niche solutions to biomedical applications, such as cell separation and mixing, droplet generation, bioprinting, and organs on a chip. Centrifugal microfluidic biochips created on compact disks show great potential in processing biological samples for point of care diagnostics. This study investigates the design and numerical simulation of an integrated microfluidic device, including a cell separation unit for isolating CTCs from a blood sample and a micromixer unit for cell lysis on a rotating disk platform. For this purpose, an inertial microfluidic device was designed for the separation of target cells by using contraction-expansion microchannel arrays. Additionally, a micromixer was incorporated to mix separated target cells with the cell lysis chemical reagent to dissolve their membranes to facilitate further assays. Our numerical simulation approach was validated for both cell separation and micromixer units and corroborates existing experimental results. In the first compartment of the proposed device (cell separation unit), several simulations were performed at different angular velocities from 500 rpm to 3000 rpm to find the optimum angular velocity for maximum separation efficiency. By using the proposed inertial separation approach, CTCs, were successfully separated from white blood cells (WBCs) with high efficiency (~90%) at an angular velocity of 2000 rpm. Furthermore, a serpentine channel with rectangular obstacles was designed to achieve a highly efficient micromixer unit with high mixing quality (~98%) for isolated CTCs lysis at 2000 rpm.
View details for DOI 10.3390/mi11070699
View details for Web of Science ID 000558282200001
View details for PubMedID 32698447
View details for PubMedCentralID PMC7407509
3D Bioprinting of Oxygenated Cell-Laden Gelatin Methacryloyl Constructs
ADVANCED HEALTHCARE MATERIALS
2020; 9 (15): e1901794
Cell survival during the early stages of transplantation and before new blood vessels formation is a major challenge in translational applications of 3D bioprinted tissues. Supplementing oxygen (O2 ) to transplanted cells via an O2 generating source such as calcium peroxide (CPO) is an attractive approach to ensure cell viability. Calcium peroxide also produces calcium hydroxide that reduces the viscosity of bioinks, which is a limiting factor for bioprinting. Therefore, adapting this solution into 3D bioprinting is of significant importance. In this study, a gelatin methacryloyl (GelMA) bioink that is optimized in terms of pH and viscosity is developed. The improved rheological properties lead to the production of a robust bioink suitable for 3D bioprinting and controlled O2 release. In addition, O2 release, bioprinting conditions, and mechanical performance of hydrogels having different CPO concentrations are characterized. As a proof of concept study, fibroblasts and cardiomyocytes are bioprinted using CPO containing GelMA bioink. Viability and metabolic activity of printed cells are checked after 7 days of culture under hypoxic condition. The results show that the addition of CPO improves the metabolic activity and viability of cells in bioprinted constructs under hypoxic condition.
View details for DOI 10.1002/adhm.201901794
View details for Web of Science ID 000540440800001
View details for PubMedID 32548961
View details for PubMedCentralID PMC7500045
Microfluidic-Based Approaches in Targeted Cell/Particle Separation Based on Physical Properties: Fundamentals and Applications
2020; 16 (29): e2000171
Cell separation is a key step in many biomedical research areas including biotechnology, cancer research, regenerative medicine, and drug discovery. While conventional cell sorting approaches have led to high-efficiency sorting by exploiting the cell's specific properties, microfluidics has shown great promise in cell separation by exploiting different physical principles and using different properties of the cells. In particular, label-free cell separation techniques are highly recommended to minimize cell damage and avoid costly and labor-intensive steps of labeling molecular signatures of cells. In general, microfluidic-based cell sorting approaches can separate cells using "intrinsic" (e.g., fluid dynamic forces) versus "extrinsic" external forces (e.g., magnetic, electric field, etc.) and by using different properties of cells including size, density, deformability, shape, as well as electrical, magnetic, and compressibility/acoustic properties to select target cells from a heterogeneous cell population. In this work, principles and applications of the most commonly used label-free microfluidic-based cell separation methods are described. In particular, applications of microfluidic methods for the separation of circulating tumor cells, blood cells, immune cells, stem cells, and other biological cells are summarized. Computational approaches complementing such microfluidic methods are also explained. Finally, challenges and perspectives to further develop microfluidic-based cell separation methods are discussed.
View details for DOI 10.1002/smll.202000171
View details for Web of Science ID 000539572300001
View details for PubMedID 32529791
Enhancement of label-free biosensing of cardiac troponin I
SPIE-INT SOC OPTICAL ENGINEERING. 2020
The detection of cardiac troponin I (cTnI) is clinically used to monitor myocardial infarctions (MI) and other heart diseases. The development of highly sensitive detection assays for cTnI is needed for the efficient diagnosis and monitoring of cTnI levels. Traditionally, enzyme-based immunoassays have been used for the detection of cTnI. However, the use of label-free sensing techniques have the advantage of potentially higher speed and lower cost for the assays. We previously reported a Photonic Crystal-Total Internal Reflection (PC-TIR) biosensor for label-free quantification of cTnI. To further improve on this, we present a comparative study between an antibody based PC-TIR sensor that relies on recombinant protein G (RPG) for the proper orientation of anti-cTnI antibodies, and an aptamer-based PC-TIR sensor for improved sensitivity and performance. Both assays relied on the use of polyethylene glycol (PEG) linkers to facilitate the modification of the sensor surfaces with biorecognition elements and to provide fluidity of the sensing surface. The aptamer-based PC-TIR sensor was successfully able to detect 0.1 ng/mL of cTnI. For the antibody-based PC-TIR sensor, the combination of the fluidity of the PEG and the increased number of active antibodies allowed for an improvement in assay sensitivity with a low detection limit of 0.01 ng/mL. The developed assays showed good performance and potential to be applied for the detection of cTnI levels in clinical samples upon further development.
View details for DOI 10.1117/12.2546979
View details for Web of Science ID 000558221300024
View details for PubMedID 32528214
View details for PubMedCentralID PMC7288396
Micro and nanoscale technologies in oral drug delivery
ADVANCED DRUG DELIVERY REVIEWS
2020; 157: 37-62
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.
View details for DOI 10.1016/j.addr.2020.07.012
View details for Web of Science ID 000600556900002
View details for PubMedID 32707147
View details for PubMedCentralID PMC7374157
Three-Dimensional Bioprinting of Functional Skeletal Muscle Tissue Using Gelatin Methacryloyl-Alginate Bioinks
2019; 10 (10)
Skeletal muscle tissue engineering aims to fabricate tissue constructs to replace or restore diseased or injured skeletal muscle tissues in the body. Several biomaterials and microscale technologies have been used in muscle tissue engineering. However, it is still challenging to mimic the function and structure of the native muscle tissues. Three-dimensional (3D) bioprinting is a powerful tool to mimic the hierarchical structure of native tissues. Here, 3D bioprinting was used to fabricate tissue constructs using gelatin methacryloyl (GelMA)-alginate bioinks. Mechanical and rheological properties of GelMA-alginate hydrogels were characterized. C2C12 myoblasts at the density 8 × 106 cells/mL were used as the cell model. The effects of alginate concentration (0, 6, and 8% (w/v)) and crosslinking mechanism (UV crosslinking or ionic crosslinking with UV crosslinking) on printability, cell viability, proliferation, and differentiation of bioinks were studied. The results showed that 10% (w/v) GelMA-8% (w/v) alginate crosslinked using UV light and 0.1 M CaCl2 provided the optimum niche to induce muscle tissue formation compared to other hydrogel compositions. Furthermore, metabolic activity of cells in GelMA bioinks was improved by addition of oxygen-generating particles to the bioinks. It is hoped that such bioprinted muscle tissues may find wide applications in drug screening and tissue regeneration.
View details for DOI 10.3390/mi10100679
View details for Web of Science ID 000494485000053
View details for PubMedID 31601016
View details for PubMedCentralID PMC6843821
- Exploring contraction-expansion inertial microfluidic-based particle separation devices integrated with curved channels AICHE JOURNAL 2019; 65 (11)
- The emergence of 3D bioprinting in organ-on-chip systems PROGRESS IN BIOMEDICAL ENGINEERING 2019; 1 (1)
Bioinks and bioprinting technologies to make heterogeneous and biomimetic tissue constructs
MATERIALS TODAY BIO
2019; 1: 100008
The native tissues are complex structures consisting of different cell types, extracellular matrix materials, and biomolecules. Traditional tissue engineering strategies have not been able to fully reproduce biomimetic and heterogeneous tissue constructs because of the lack of appropriate biomaterials and technologies. However, recently developed three-dimensional bioprinting techniques can be leveraged to produce biomimetic and complex tissue structures. To achieve this, multicomponent bioinks composed of multiple biomaterials (natural, synthetic, or hybrid natural-synthetic biomaterials), different types of cells, and soluble factors have been developed. In addition, advanced bioprinting technologies have enabled us to print multimaterial bioinks with spatial and microscale resolution in a rapid and continuous manner, aiming to reproduce the complex architecture of the native tissues. This review highlights important advances in heterogeneous bioinks and bioprinting technologies to fabricate biomimetic tissue constructs. Opportunities and challenges to further accelerate this research area are also described.
View details for DOI 10.1016/j.mtbio.2019.100008
View details for Web of Science ID 000546326200005
View details for PubMedID 32159140
View details for PubMedCentralID PMC7061634