Publications by authors named "Woojung Shin"

17 Publications

  • Page 1 of 1

Multiplex recreation of human intestinal morphogenesis on a multi-well insert platform by basolateral convective flow.

Lab Chip 2021 Jul 29. Epub 2021 Jul 29.

Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, South Korea. and Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), 77, Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea and Institute for Convergence Research and Education in Advanced Technology, Yonsei University, 50, Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Here, we report a multiplex culture system that enables simultaneous recreation of multiple replications of the three-dimensional (3D) microarchitecture of the human intestinal epithelium in vitro. The "basolateral convective flow-generating multi-well insert platform (BASIN)" contains 24 nano-porous inserts and an open basolateral chamber applying controllable convective flow in the basolateral compartment that recreates a biomimetic morphogen gradient using a conventional orbital shaker. The mechanistic approach by which the removal of morphogen inhibitors in the basolateral medium can induce intestinal morphogenesis was applied to manipulate the basolateral convective flow in space and time. In a multiplex BASIN, we successfully regenerated a 3D villi-like intestinal microstructure using the Caco-2 human intestinal epithelium that presents high barrier function with minimal insert-to-insert variations. The enhanced cytodifferentiation and proliferation of the 3D epithelial layers formed in the BASIN were visualized with markers of absorptive (villin) and proliferative cells (Ki67). The paracellular transport and efflux profiles of the microengineered 3D epithelial layers in the BASIN confirmed its reproducibility, robustness, and scalability for multiplex biochemical or pharmaceutical studies. Finally, the BASIN was used to investigate the effects of dextran sodium sulfate on the intestinal epithelial barrier and morphology to validate its practical applicability for investigating the effects of external chemicals on the intestinal epithelium and constructing a leaky-gut model. We envision that the BASIN may provide an improved multiplex, scalable, and physiological intestinal epithelial model that is readily accessible to researchers in both basic and applied sciences.
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http://dx.doi.org/10.1039/d1lc00404bDOI Listing
July 2021

Robust Formation of an Epithelial Layer of Human Intestinal Organoids in a Polydimethylsiloxane-Based Gut-on-a-Chip Microdevice.

Front Med Technol 2020 Aug 7;2. Epub 2020 Aug 7.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States.

Polydimethylsiloxane (PDMS) is a silicone polymer that has been predominantly used in a human organ-on-a-chip microphysiological system. The hydrophobic surface of a microfluidic channel made of PDMS often results in poor adhesion of the extracellular matrix (ECM) as well as cell attachment. The surface modification by plasma or UV/ozone treatment in a PDMS-based device produces a hydrophilic surface that allows robust ECM coating and the reproducible attachment of human intestinal immortalized cell lines. However, these surface-activating methods have not been successful in forming a monolayer of the biopsy-derived primary organoid epithelium. Several existing protocols to grow human intestinal organoid cells in a PDMS microchannel are not always reproducibly operative due to the limited information. Here, we report an optimized methodology that enables robust and reproducible attachment of the intestinal organoid epithelium in a PDMS-based gut-on-a-chip. Among several reported protocols, we optimized a method by performing polyethyleneimine-based surface functionalization followed by the glutaraldehyde cross linking to activate the PDMS surface. Moreover, we discovered that the post-functionalization step contributes to provide uniform ECM deposition that allows to produce a robust attachment of the dissociated intestinal organoid epithelium in a PDMS-based microdevice. We envision that our optimized protocol may disseminate an enabling methodology to advance the integration of human organotypic cultures in a human organ-on-a-chip for patient-specific disease modeling.
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http://dx.doi.org/10.3389/fmedt.2020.00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849371PMC
August 2020

Spatiotemporal Gradient and Instability of Wnt Induce Heterogeneous Growth and Differentiation of Human Intestinal Organoids.

iScience 2020 Aug 16;23(8):101372. Epub 2020 Jul 16.

Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton St., Austin, TX 78712, USA; Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA; Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address:

In a conventional culture of three-dimensional human intestinal organoids, extracellular matrix hydrogel has been used to provide a physical space for the growth and morphogenesis of organoids in the presence of exogenous morphogens such as Wnt3a. We found that organoids embedded in a dome-shaped hydrogel show significant size heterogeneity in different locations inside the hydrogel. Computational simulations revealed that the instability and diffusion limitation of Wnt3a constitutively generate a concentration gradient inside the hydrogel. The location-dependent heterogeneity of organoids in a hydrogel dome substantially perturbed the transcriptome profile associated with epithelial functions, cytodifferentiation including mucin 2 expression, and morphological characteristics. This heterogeneous phenotype was significantly mitigated when the Wnt3a was frequently replenished in the culture medium. Our finding suggests that the morphological, transcriptional, translational, and functional heterogeneity in conventional organoid cultures may lead to a false interpretation of the experimental results in organoid-based studies.
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http://dx.doi.org/10.1016/j.isci.2020.101372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398973PMC
August 2020

Engineering Microphysiological Immune System Responses on Chips.

Trends Biotechnol 2020 08 18;38(8):857-872. Epub 2020 Feb 18.

Department of Bioengineering, University of Washington, Seattle, WA 98109, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

Tissues- and organs-on-chips are microphysiological systems (MPSs) that model the architectural and functional complexity of human tissues and organs that is lacking in conventional cell monolayer cultures. While substantial progress has been made in a variety of tissues and organs, chips recapitulating immune responses have not advanced as rapidly. This review discusses recent progress in MPSs for the investigation of immune responses. To illustrate recent developments, we focus on two cases in point: immunocompetent tumor microenvironment-on-a-chip devices that incorporate stromal and immune cell components and pathomimetic modeling of human mucosal immunity and inflammatory crosstalk. More broadly, we discuss the development of systems immunology-on-a-chip devices that integrate microfluidic engineering approaches with high-throughput omics measurements and emerging immunological applications of MPSs.
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http://dx.doi.org/10.1016/j.tibtech.2020.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368088PMC
August 2020

Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.

Micromachines (Basel) 2020 Jul 7;11(7). Epub 2020 Jul 7.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.

The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.
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http://dx.doi.org/10.3390/mi11070663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408321PMC
July 2020

Microphysiological Engineering of Immune Responses in Intestinal Inflammation.

Immune Netw 2020 Apr 8;20(2):e13. Epub 2020 Apr 8.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.

The epithelial barrier in the gastrointestinal (GI) tract is a protective interface that endures constant exposure to the external environment while maintaining its close contact with the local immune system. Growing evidence has suggested that the intercellular crosstalk in the GI tract contributes to maintaining the homeostasis in coordination with the intestinal microbiome as well as the tissue-specific local immune elements. Thus, it is critical to map the complex crosstalks in the intestinal epithelial-microbiome-immune (EMI) axis to identify a pathological trigger in the development of intestinal inflammation, including inflammatory bowel disease. However, deciphering a specific contributor to the onset of pathophysiological cascades has been considerably hindered by the challenges in current and models. Here, we introduce various microphysiological engineering models of human immune responses in the EMI axis under the healthy conditions and gut inflammation. As a prospective model, we highlight how the human "gut inflammation-on-a-chip" can reconstitute the pathophysiological immune responses and contribute to understanding the independent role of inflammatory factors in the EMI axis on the initiation of immune responses under barrier dysfunction. We envision that the microengineered immune models can be useful to build a customizable patient's chip for the advance in precision medicine.
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http://dx.doi.org/10.4110/in.2020.20.e13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192834PMC
April 2020

Recapitulation of the accessible interface of biopsy-derived canine intestinal organoids to study epithelial-luminal interactions.

PLoS One 2020 17;15(4):e0231423. Epub 2020 Apr 17.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States of America.

Recent advances in canine intestinal organoids have expanded the option for building a better in vitro model to investigate translational science of intestinal physiology and pathology between humans and animals. However, the three-dimensional geometry and the enclosed lumen of canine intestinal organoids considerably hinder the access to the apical side of epithelium for investigating the nutrient and drug absorption, host-microbiome crosstalk, and pharmaceutical toxicity testing. Thus, the creation of a polarized epithelial interface accessible from apical or basolateral side is critical. Here, we demonstrated the generation of an intestinal epithelial monolayer using canine biopsy-derived colonic organoids (colonoids). We optimized the culture condition to form an intact monolayer of the canine colonic epithelium on a nanoporous membrane insert using the canine colonoids over 14 days. Transmission and scanning electron microscopy revealed a physiological brush border interface covered by the microvilli with glycocalyx, as well as the presence of mucin granules, tight junctions, and desmosomes. The population of stem cells as well as differentiated lineage-dependent epithelial cells were verified by immunofluorescence staining and RNA in situ hybridization. The polarized expression of P-glycoprotein efflux pump was confirmed at the apical membrane. Also, the epithelial monolayer formed tight- and adherence-junctional barrier within 4 days, where the transepithelial electrical resistance and apparent permeability were inversely correlated. Hence, we verified the stable creation, maintenance, differentiation, and physiological function of a canine intestinal epithelial barrier, which can be useful for pharmaceutical and biomedical researches.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231423PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164685PMC
July 2020

"Good Fences Make Good Neighbors": How does the Human Gut Microchip Unravel Mechanism of Intestinal Inflammation?

Gut Microbes 2020 05 14;11(3):581-586. Epub 2019 Jun 14.

Department of Biomedical Engineering, The University of Texas at Austin , Austin, TX, USA.

A microengineered human gut-on-a-chip has demonstrated intestinal physiology, three-dimensional (3D) epithelial morphogenesis, and longitudinal host-microbiome interactions . The modular accessibility and modularity of the microphysiological gut-on-a-chip can lead to the identification of the seminal trigger in intestinal inflammation. By coupling microbial and immune cells in a spatiotemporal manner, we discovered that the maintenance of healthy epithelial barrier function is necessary and sufficient to demonstrate the homeostatic tolerance of the gut. Here, we highlight the breakthrough of our new disease model and discuss the future impact of investigating the etiology and therapeutic targets in the multifactorial inflammatory bowel disease.
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http://dx.doi.org/10.1080/19490976.2019.1626684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524309PMC
May 2020

Human Intestinal Morphogenesis Controlled by Transepithelial Morphogen Gradient and Flow-Dependent Physical Cues in a Microengineered Gut-on-a-Chip.

iScience 2019 May 3;15:391-406. Epub 2019 May 3.

Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX 78712, USA; Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA; Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address:

We leveraged a human gut-on-a-chip (Gut Chip) microdevice that enables independent control of fluid flow and mechanical deformations to explore how physical cues and morphogen gradients influence intestinal morphogenesis. Both human intestinal Caco-2 and intestinal organoid-derived primary epithelial cells formed three-dimensional (3D) villi-like microarchitecture when exposed to apical and basal fluid flow; however, 3D morphogenesis did not occur and preformed villi-like structure involuted when basal flow was ceased. When cells were cultured in static Transwells, similar morphogenesis could be induced by removing or diluting the basal medium. Computational simulations and experimental studies revealed that the establishment of a transepithelial gradient of the Wnt antagonist Dickkopf-1 and flow-induced regulation of the Frizzled-9 receptor mediate the histogenesis. Computational simulations also predicted spatial growth patterns of 3D epithelial morphology observed experimentally in the Gut Chip. A microengineered Gut Chip may be useful for studies analyzing stem cell biology and tissue development.
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http://dx.doi.org/10.1016/j.isci.2019.04.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526295PMC
May 2019

A Robust Longitudinal Co-culture of Obligate Anaerobic Gut Microbiome With Human Intestinal Epithelium in an Anoxic-Oxic Interface-on-a-Chip.

Front Bioeng Biotechnol 2019 7;7:13. Epub 2019 Feb 7.

Department of Biomedical Engineering, The University of Texas at Austin Austin, TX, United States.

The majority of human gut microbiome is comprised of obligate anaerobic bacteria that exert essential metabolic functions in the human colon. These anaerobic gut bacteria constantly crosstalk with the colonic epithelium in a mucosal anoxic-oxic interface (AOI). However, recreation of the metabolically mismatched colonic AOI has been technically challenging. Furthermore, stable co-culture of the obligate anaerobic commensal microbiome and epithelial cells in a mechanically dynamic condition is essential for demonstrating the host-gut microbiome crosstalk. Here, we developed an anoxic-oxic interface-on-a-chip (AOI Chip) by leveraging a modified human gut-on-a-chip to demonstrate a controlled oxygen gradient in the lumen-capillary transepithelial interface by flowing anoxic and oxic culture medium at various physiological milieus. Computational simulation and experimental results revealed that the presence of the epithelial cell layer and the flow-dependent conditioning in the lumen microchannel is necessary and sufficient to create the steady-state vertical oxygen gradient in the AOI Chip. We confirmed that the created AOI does not compromise the viability, barrier function, mucin production, and the expression and localization of tight junction proteins in the 3D intestinal epithelial layer. Two obligate anaerobic commensal gut microbiome, and , that exert metabolic cross-feeding , were independently co-cultured with epithelial cells in the AOI Chip for up to a week without compromising any cell viability. Our new protocol for creating an AOI in a microfluidic gut-on-a-chip may enable to demonstrate the key physiological interactions of obligate anaerobic gut microbiome with the host cells associated with intestinal metabolism, homeostasis, and immune regulation.
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http://dx.doi.org/10.3389/fbioe.2019.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374617PMC
February 2019

Intestinal barrier dysfunction orchestrates the onset of inflammatory host-microbiome cross-talk in a human gut inflammation-on-a-chip.

Proc Natl Acad Sci U S A 2018 11 22;115(45):E10539-E10547. Epub 2018 Oct 22.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712;

The initiation of intestinal inflammation involves complex intercellular cross-talk of inflammatory cells, including the epithelial and immune cells, and the gut microbiome. This multicellular complexity has hampered the identification of the trigger that orchestrates the onset of intestinal inflammation. To identify the initiator of inflammatory host-microbiome cross-talk, we leveraged a pathomimetic "gut inflammation-on-a-chip" undergoing physiological flow and motions that recapitulates the pathophysiology of dextran sodium sulfate (DSS)-induced inflammation in murine models. DSS treatment significantly impaired, without cytotoxic damage, epithelial barrier integrity, villous microarchitecture, and mucus production, which were rapidly recovered after cessation of DSS treatment. We found that the direct contact of DSS-sensitized epithelium and immune cells elevates oxidative stress, in which the luminal microbial stimulation elicited the production of inflammatory cytokines and immune cell recruitment. In contrast, an intact intestinal barrier successfully suppressed oxidative stress and inflammatory cytokine production against the physiological level of lipopolysaccharide or nonpathogenic in the presence of immune elements. Probiotic treatment effectively reduced the oxidative stress, but it failed to ameliorate the epithelial barrier dysfunction and proinflammatory response when the probiotic administration happened after the DSS-induced barrier disruption. Maintenance of epithelial barrier function was necessary and sufficient to control the physiological oxidative stress and proinflammatory cascades, suggesting that "good fences make good neighbors." Thus, the modular gut inflammation-on-a-chip identifies the mechanistic contribution of barrier dysfunction mediated by intercellular host-microbiome cross-talk to the onset of intestinal inflammation.
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http://dx.doi.org/10.1073/pnas.1810819115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233106PMC
November 2018

Pathomimetic modeling of human intestinal diseases and underlying host-gut microbiome interactions in a gut-on-a-chip.

Methods Cell Biol 2018 25;146:135-148. Epub 2018 Jun 25.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States. Electronic address:

The gut-on-a-chip is a microengineered in vitro model of the living human intestine that reconstitutes the lumen-capillary tissue interface. Intestinal epithelial Caco-2 cells cultured on the extracellular matrix-coated porous membrane in a gut-on-a-chip undergo three-dimensional villus morphogenesis and physiological cytodifferentiation. The gut-on-a-chip closely recapitulates biomechanical and functional characteristics under peristalsis-like cyclic movements and trickling flow, which enables to co-culture gut microbiome with villus epithelium from days to weeks. Host-gut microbiome ecosystem emulated in the gut-on-a-chip allows the pathomimetic modeling of human intestinal diseases such as gut inflammation and bacterial overgrowth. Here, we describe a protocol for microfabrication of a gut-on-a-chip device, reconstitution of intestinal microenvironment, recreation of host-gut microbiome intercellular interactions, and demonstration of the pathophysiology of representative human intestinal diseases associated with the gut microbiome. The modeling of intestinal disease pathophysiology on-chip can potentiate the development of patient-specific disease models that can validate the efficacy and safety of novel therapeutic interventions.
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http://dx.doi.org/10.1016/bs.mcb.2018.05.006DOI Listing
December 2018

Microfluidic Organ-on-a-Chip Models of Human Intestine.

Cell Mol Gastroenterol Hepatol 2018 24;5(4):659-668. Epub 2018 Apr 24.

Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.

Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology and pathophysiology. In this article, we review this field and describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability to analyze contributions of individual cellular, chemical, and physical control parameters one-at-a-time; to coculture human intestinal cells with commensal microbiome for extended times; and to create human-relevant disease models. We also discuss potential future applications of human Intestine Chips, including how they might be used for drug development and personalized medicine.
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http://dx.doi.org/10.1016/j.jcmgh.2017.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924739PMC
April 2018

Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro.

Stem Cell Rev Rep 2017 Jun;13(3):321-334

Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton St. BME 4.202C, Austin, TX, 78712, USA.

The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human. However, controlling the multi-species microbial communities and their uncontrolled growth has remained a notable technical challenge. Furthermore, conventional two-dimensional (2D) or 3D culture systems do not recapitulate multicellular microarchitectures, mechanical dynamics, and tissue-specific functions. Here, we review recent advances and current pitfalls of in vitro and ex vivo models that display human GI functions. We also discuss how the disruptive technologies such as 3D organoids or a human organ-on-a-chip microphysiological system can contribute to better emulate host-gut microbiome crosstalks in health and disease. Finally, the medical and pharmaceutical significance of the gut microbiome-based personalized interventions is underlined as a future perspective.
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http://dx.doi.org/10.1007/s12015-017-9739-zDOI Listing
June 2017

Photothermal-modulated drug delivery and magnetic relaxation based on collagen/poly(γ-glutamic acid) hydrogel.

Int J Nanomedicine 2017 31;12:2607-2620. Epub 2017 Mar 31.

SKKU Advanced Institute of Nanotechnology (SAINT).

Injectable and stimuli-responsive hydrogels have attracted attention in molecular imaging and drug delivery because encapsulated diagnostic or therapeutic components in the hydrogel can be used to image or change the microenvironment of the injection site by controlling various stimuli such as enzymes, temperature, pH, and photonic energy. In this study, we developed a novel injectable and photoresponsive composite hydrogel composed of anticancer drugs, imaging contrast agents, bio-derived collagen, and multifaceted anionic polypeptide, poly (γ-glutamic acid) (γ-PGA). By the introduction of γ-PGA, the intrinsic temperature-dependent phase transition behavior of collagen was modified to a low viscous sol state at room temperature and nonflowing gel state around body temperature. The modified temperature-dependent phase transition behavior of collagen/γ-PGA hydrogels was also evaluated after loading of near-infrared (NIR) fluorophore, indocyanine green (ICG), which could transform absorbed NIR photonic energy into thermal energy. By taking advantage of the abundant carboxylate groups in γ-PGA, cationic-charged doxorubicin (Dox) and hydrophobic MnFeO magnetic nanoparticles were also incorporated successfully into the collagen/γ-PGA hydrogels. By illumination of NIR light on the collagen/γ-PGA/Dox/ICG/MnFeO hydrogels, the release kinetics of Dox and magnetic relaxation of MnFeO nanoparticles could be modulated. The experimental results suggest that the novel injectable and NIR-responsive collagen/γ-PGA hydrogels developed in this study can be used as a theranostic platform after loading of various molecular imaging probes and therapeutic components.
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http://dx.doi.org/10.2147/IJN.S133078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383084PMC
June 2017

Priming nanoparticle-guided diagnostics and therapeutics towards human organs-on-chips microphysiological system.

Nano Converg 2016 1;3(1):24. Epub 2016 Oct 1.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712 USA ; School of Medicine, Pusan National University, Yangsan, 50612 Republic of Korea.

Nanotechnology and bioengineering have converged over the past decades, by which the application of multi-functional nanoparticles (NPs) has been emerged in clinical and biomedical fields. The NPs primed to detect disease-specific biomarkers or to deliver biopharmaceutical compounds have beena validated in conventional in vitro culture models including two dimensional (2D) cell cultures or 3D organoid models. However, a lack of experimental models that have strong human physiological relevance has hampered accurate validation of the safety and functionality of NPs. Alternatively, biomimetic human "Organs-on-Chips" microphysiological systems have recapitulated the mechanically dynamic 3D tissue interface of human organ microenvironment, in which the transport, cytotoxicity, biocompatibility, and therapeutic efficacy of NPs and their conjugates may be more accurately validated. Finally, integration of NP-guided diagnostic detection and targeted nanotherapeutics in conjunction with human organs-on-chips can provide a novel avenue to accelerate the NP-based drug development process as well as the rapid detection of cellular secretomes associated with pathophysiological processes.
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http://dx.doi.org/10.1186/s40580-016-0084-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5271165PMC
October 2016

A Fluorescent Tile DNA Diagnocode System for In Situ Rapid and Selective Diagnosis of Cytosolic RNA Cancer Markers.

Sci Rep 2015 Dec 18;5:18497. Epub 2015 Dec 18.

School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea.

Accurate cancer diagnosis often requires extraction and purification of genetic materials from cells, and sophisticated instrumentations that follow. Otherwise in order to directly treat the diagnostic materials to cells, multiple steps to optimize dose concentration and treatment time are necessary due to diversity in cellular behaviors. These processes may offer high precision but hinder fast analysis of cancer, especially in clinical situations that need rapid detection and characterization of cancer. Here we present a novel fluorescent tile DNA nanostructure delivered to cancer cytosol by employing nanoparticle technology. Its structural anisotropicity offers easy manipulation for multifunctionalities, enabling the novel DNA nanostructure to detect intracellular cancer RNA markers with high specificity within 30 minutes post treatment, while the nanoparticle property bypasses the requirement of treatment optimization, effectively reducing the complexity of applying the system for cancer diagnosis. Altogether, the system offers a precise and rapid detection of cancer, suggesting the future use in the clinical fields.
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http://dx.doi.org/10.1038/srep18497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683441PMC
December 2015
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