Multifunctional Bioreactor System for Human Intestine Tissues

Zhou, Wenda; Chen, Ying; Roh, Terrence T.; Lin, Yi-Nan; Ling, Shengjie; Zhao, Siwei; Lin, James; Khalil, Noor; Cairns, Dana M.; Manousiouthakis, Eleana; Tse, Megan W.; Kaplan, David L.

doi:10.1021/acsbiomaterials.7b00794

Cited by 44 publications

(36 citation statements)

References 28 publications

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“…Porous polymeric structures as an extracellular matrix (ECM) analogue provide a spatial conformation and orientation to cells and permits nutrient transport, fulfilling a pivotal role in tissue engineering [1][2] . The control of porosity and pore shape is crucial for the polymeric membranes and scaffolds since the size of the pores directs the cell and nutrition transport through the scaffold 3 .…”

Section: Introductionmentioning

confidence: 99%

Honeycomb-like PLGA-b-PEG Structure Creation with T-Junction Microdroplets

Gultekinoglu¹,

Jiang

Bayram³

et al. 2018

Langmuir

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Amphiphilic block copolymers are widely used in science owing to their versatile properties. In this study, amphiphilic block copolymer poly(lactic- co-glycolic acid)- block-poly(ethylene glycol) (PLGA- b-PEG) was used to create microdroplets in a T-junction microfluidic device with a well-defined geometry. To compare interfacial characteristics of microdroplets, dichloromethane (DCM) and chloroform were used to prepare PLGA- b-PEG solution as an oil phase. In the T-junction device, water and oil phases were manipulated at variable flow rates from 50 to 300 μL/min by increments of 50 μL/min. Fabricated microdroplets were directly collected on a glass slide. After a drying period, porous two-dimensional and three-dimensional structures were obtained as honeycomb-like structure. Pore sizes were increased according to increased water/oil flow rate for both DCM and chloroform solutions. Also, it was shown that increasing polymer concentration decreased the pore size of honeycomb-like structures at a constant water/oil flow rate (50:50 μL/min). Additionally, PLGA- b-PEG nanoparticles were also obtained on the struts of honeycomb-like structures according to the water solubility, volatility, and viscosity properties of oil phases, by the aid of Marangoni flow. The resulting structures have a great potential to be used in biomedical applications, especially in drug delivery-related studies, with nanoparticle forming ability and cellular responses in different surface morphologies.

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Section: Introductionmentioning

confidence: 99%

Honeycomb-like PLGA-b-PEG Structure Creation with T-Junction Microdroplets

Gultekinoglu¹,

Jiang

Bayram³

et al. 2018

Langmuir

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“…Many tissue engineering protocols rely on multi-day culture timelines and numerous reagents to evaluate products [34][35][36][37]. Reactors housing organs or vessels require calibrated perfusion [38][39][40]. Scale-up and product transport remain challenges for tissue engineered products [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

3D Printed Model of Extrahepatic Biliary Ducts for Biliary Stent Testing

et al. 2020

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Several inflammatory conditions of the bile ducts cause strictures that prevent the drainage of bile into the gastrointestinal tract. Non-pharmacological treatments to re-establish bile flow include plastic or self-expanding metal stents (SEMs) that are inserted in the bile ducts during endoscopic retrograde cholangiopancreatography (ERCP) procedures. The focus of this study was to 3D print an anatomically accurate model of the extrahepatic bile ducts (EHBDs) with tissue-like mechanical properties to improve in vitro testing of stent prototypes. Following generation of an EHBD model via computer aided design (CAD), we tested the ability of Formlabs SLA 3D printers to precisely print the model with polymers selected based on the desired mechanical properties. We found the printers were reliable in printing the dimensionally accurate EHBD model with candidate polymers. Next, we evaluated the mechanical properties of Formlabs Elastic (FE), Flexible (FF), and Durable (FD) resins pre- and post-exposure to water, saline, or bile acid solution at 37 °C for up to one week. FE possessed the most bile duct-like mechanical properties based on its elastic moduli, percent elongations at break, and changes in mass under all liquid exposure conditions. EHBD models printed in FE sustained no functional damage during biliary stent deployment or when tube connectors were inserted, and provided a high level of visualization of deployed stents. These results demonstrate that our 3D printed EHBD model facilitates more realistic pre-clinical in vitro testing of biliary stent prototypes.

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“…This method is on a much smaller scale than the hollow fiber cartridges and cannot produce large quantities of oocysts, but it may be more amenable to moderate-throughput screening or in vitro propagation of transgenic C. parvum lines. The authors have also adapted these 3D silk scaffolds into a multifunctional bioreactor to create a dynamic culture environment, allowing for control of oxygen levels in perfusion fluids, as well as the mechanical and chemical microenvironments present in human intestines [113]. The bioreactor system may be a much more physiologically relevant environment in which to study co-cultures of human pathogens such as Cryptosporidium.…”

Section: Advances In In Vitro Culturing Methodsmentioning

confidence: 99%

Phenotypic screening techniques forCryptosporidiumdrug discovery

Love

McNamara

2020

Expert Opinion on Drug Discovery

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Introduction: Two landmark epidemiological studies identified Cryptosporidium spp. as a significant cause of diarrheal disease in pediatric populations in resource-limited countries. Notably, nitazoxanide is the only approved drug for treatment of cryptosporidiosis but shows limited efficacy. As a result, many drug discovery efforts have commenced to find improved treatments. The unique biology of Cryptosporidium presents challenges for traditional drug discovery methods, which has inspired new assay platforms to study parasite biology and drug screening. Areas covered: The authors review historical advancements in phenotypic-based assays and techniques for Cryptosporidium drug discovery, as well as recent advances that will define future drug discovery. The reliance on phenotypic-based screens and repositioning of phenotypic hits from other pathogens has quickly created a robust pipeline of potential cryptosporidiosis therapeutics. The latest advances involve new in vitro culture methods for oocyst generation, continuous culturing capabilities, and more physiologically relevant assays for testing compounds. Expert opinion: Previous phenotypic screening techniques have laid the groundwork for recent cryptosporidiosis drug discovery efforts. The resulting improved methodologies characterize compound activity, identify, and validate drug targets, and prioritize new compounds for drug development. The most recent improvements in phenotypic assays are poised to help advance compounds into clinical development.

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Multifunctional Bioreactor System for Human Intestine Tissues

Cited by 44 publications

References 28 publications

Honeycomb-like PLGA-b-PEG Structure Creation with T-Junction Microdroplets

Honeycomb-like PLGA-b-PEG Structure Creation with T-Junction Microdroplets

3D Printed Model of Extrahepatic Biliary Ducts for Biliary Stent Testing

Phenotypic screening techniques forCryptosporidiumdrug discovery

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