Bioreactor technologies to support liver function in vitro

Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drives efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models.National Institutes of Health (U.S.) (R01 EB010246)National Institutes of Health (U.S.) (P50-GM068762-08)National Institutes of Health (U.S.) (R01-ES015241)National Institutes of Health (U.S.) (P30-ES002109)5UH2TR000496-02National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (CBET-0939511)United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039

Nanoparticle functionalized laser patterned substrate: an innovative route towards low cost biomimetic platforms

Integration of nanotechnology and advanced manufacturing processes presents an attractive route to produce devices for adaptive biomedical device technologies. However, tailoring biological, physical, and chemical properties often leads to complex processing steps and therefore to high manufacturing cost impeding further scalability. Herein, a novel laser-based approach is introduced to manufacture low cost biocompatible polymer substrates functionalized with ultrapure nanoparticles. Laser direct writing was performed to create micron-sized patterns on 188 μm-thick cyclic olefin polymer (COP) substrates using a picosecond pulsed 1064 nm Nd:YAG laser. The Pulsed Laser Ablation in Liquids (PLAL) technique was exploited in this work to prepare colloidal solutions of ultrapure nanoparticles to impart bio-functionality onto laser patterned surfaces. Combining the laser patterns and their modification with PLAL-nanoparticles resulted in a functional and biocompatible substrate for biosensing applications. Our in vitro cell viability studies using a model cell line (human skin keratinocyte, HaCaT) suggest that these nanoparticles immobilized on the surfaces function as a biomimetic platform with the ability to interact with different biological entities (e.g. DNA, antibodies etc.)

Development of On-Line High Performance Liquid Chromatography (HPLC)-Biochemical Detection Methods as Tools in the Identification of Bioactives

Biochemical detection (BCD) methods are commonly used to screen plant extracts for specific biological activities in batch assays. Traditionally, bioactives in the most active extracts were identified through time-consuming bio-assay guided fractionation until single active compounds could be isolated. Not only are isolation procedures often tedious, but they could also lead to artifact formation. On-line coupling of BCD assays to high performance liquid chromatography (HPLC) is gaining ground as a high resolution screening technique to overcome problems associated with pre-isolation by measuring the effects of compounds post-column directly after separation. To date, several on-line HPLC-BCD assays, applied to whole plant extracts and mixtures, have been published. In this review the focus will fall on enzyme-based, receptor-based and antioxidant assays

Microtechnology-based organ systems and whole-body models for drug screening

After drug administration, the drugs are absorbed, distributed, metabolized, and excreted (ADME). Because ADME processes affect drug efficacy, various in vitro models have been developed based on the ADME processes. Although these models have been widely accepted as a tool for predicting the effects of drugs, the differences between in vivo and in vitro systems result in high attrition rates of drugs during the development process and remain a major limitation. Recent advances in microtechnology enable more accurate mimicking of the in vivo environment, where cellular behavior and physiological responses to drugs are more realistic; this has led to the development of novel in vitro systems, known as organ-on-a-chip systems. The development of organ-on-a-chip systems has progressed to include the reproduction of multiple organ interactions, which is an important step towards body-on-a-chip systems that will ultimately predict whole-body responses to drugs. In this review, we summarize the application of microtechnology for the development of in vitro systems that accurately mimic in vivo environments and reconstruct multiple organ models.OAIID:RECH_ACHV_DSTSH_NO:T201623717RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A002014CITE_RATE:3.781FILENAME:3. (2016.06) Microtechnology-based organ systems and.pdfDEPT_NM:화학생물공학부EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/ce1256c8-4084-4576-aa21-3470ab81611a/linkCONFIRM: