Search Results for '3d cell culture systems'

  1. Why is the application of 3D Bioprinting important in Drug Development?

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    Drug development is a time-consuming and expensive process that proceeds through several stages from target identification to lead discovery and optimization, preclinical validation, and clinical trials, ending up in approval for clinical use. It is well known that 90 percent of drugs that reach clinical stage development never make it to FDA approval and commercialization. The cost of a failed drug is between $800m and £1.4bn. With this low success rate in clinical trials, drug discovery remains a slow and costly business. Hence, there is an urgent need for new technologies which can mitigate the risk of failures.

    3D bioprinting is one of the most promising areas expected to improve the success rates in drug development. Whilst most people start to imagine printed human organs for transplanting into the patients when they hear the word bioprinting, in realitywe probably won’t see 3D printed, transplantable human organs for many years yet. Internal organs are more complex than simply printing layers of cells into the shape of a kidney or liver. They need to have nerves and blood vessels to function and survive, and bioprinting technology still has a way to go before reaching the required level of complexity.

    The most realistic application of 3D Bioprinting in this decade will most likely be  in drug discovery and development. In the pharma industry, the companies test drugs on animals before the drugs go to expensive clinical trials. However, the human physiology is very different from that of test animals, so what works in an animal, will not necessarily be effective in a person.

    Bioprinting can be used to print a range of 3D culture systems and human tissue models to produce better in vitro testing by generating models with improved physiological relevance and high reproducibility. By applying bioprinting in drug discovery and development organisations can identify ineffective or harmful drugs earlier in the discovery process and shift their resources to more promising drug candidates. They can also reduce the cost of drug development caused by clinical trial failures.

    Organovo’s bioprinted ExVive liver tissues have already proven useful in preclinical toxicology assessment. According to Organovo, the market for liver and kidney in vivo tissue testing is currently valued at close to $3 billion combined1. 3D bioprinting has also been shown to enable the investigation of cancer progression, including tumour heterogeneity, cancer metastasis, and patient specific anticancer drug testing. As bioprinting proves to be a cost-effective and efficient solution, its value in this field is expected to grow from the current $11 million to several hundred millions of dollars over the next decade1.

     

    1SmartTechMarkets (2017) Use Of 3D Bioprinting In Drug Discovery And Cosmetics Testing Expected To Reach $500 Million By 2027 [link]

     

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  2. Biogelx hydrogels utilized to generate a 3D model of a human epiblast

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    An article by MijoSimunovic and colleagues from the Brivanlou and Siggia labs at The Rockefeller University in New York City showcases the use of Biogelx hydrogels in a 3D model of a human epiblast.

    The authors used human embryonic stem cells (hECSs) to create an in vitro 3D model of an epiblast in which size, cell polarity, and gene expression mimicked those of a 10-day human epiblast.

    The epiblast is a polarized epithelium, which will give rise to all cells of the fetus. During gastrulation, the three body axes (anterior-posterior, dorsal-ventral and the left-right axes) are created, establishing the vertebrate body plan. Mouse gastrulation 3D models (called gastruloids) have been previously generated from mouse embryonic stem cells (mESCs), and the morphogenetic movements that establish body symmetry at gastrulation and much of the signaling network underlying these processes have been elucidated in the mouse. However, some of these complex mechanisms are different in humans. Moreover, directly studying human gastrulation and human embryonic development is very challenging due to ethical guidelines (among other considerations) and has been largely unexplored. Therefore, synthetic models of human embryos are needed to address these questions.

    In this work, the authors initallly used Matrigel to culture 3D hESC colonies, however observed the cells differentiated despite the absence of added morphogens. Thus, the researchers concluded that they could not use a Matrigel system to model a pre-gastrulating human epiblast. To improve culture conditions, Simunovic and colleagues utilized Biogelx peptide hydrogel as the 3D matrix.They observed how the 3D hESC colonies displayed “…similar size range, morphology, molecular markers, and tissue polarity that matched our in vitro attached 10-day human embryos”. Furthermore, cells cultured in this 3D model formed a quasi-spherical hollow shell and uniformly expressed key biomarkers like NANOG, SOX2, and OCT4 unlike in pure Matrigel. Additional parameters like the radius of the human epiblast and the surface cell density compared very well with their model epiblast.

    This shows how Biogelx, a peptide hydrogel with defined composition and controlled chemical and mechanical properties proves to be very useful in modelling complex systems which are aim to elucidate intricate processes. Biogelx gels can be utilized either combined with other biomaterials or on their own; especially when using the new functionalized products which are based on the original Biogelx technology, but also contain specific biomimetic sequences relevant to the ECM and basement membrane proteins.

    REFERENCES: Simunovic et al. (2018) Molecular mechanism of symmetry breaking in a 3D model of a human epiblast.bioRxiv 330704.

    You can read the full article here.

     

     

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  3. Disease-driven Changes in the Extracellular Matrix

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    It is widely accepted that cell-based assays traditionally performed in 2D on plastic surfaces are not representative of cells residing in the complex microenvironment of a tissue. This discrepancy is thought to make these systems relatively poor models to predict drug responses, and therefore a contributing factor to the high failure rate in drug discovery. It is believed that 3D cell culture can better reproduce the physiochemical environment of in vivo tissue, providing cells mechanical and biochemical cues like those of native ECM. Therefore, it can provide more physiologically-relevant results, which can ultimately lead to better precision in drug discovery. Despite increased focus, major challenges remain in creating 3D cell-based assays which are reproducible and can recapitulate microenvironmental factors that resemble in vivo tissue as well as disease pathology.

    From the smoothness of brain tissue to the toughness of bone, the mechanical properties of organs vary dramatically. The differences in these environments arise through cells secreting various ECM proteins and macromolecules in different proportionsin addition to intrinsic phenotypic intracellular cell type differences. Whilst such environments are regulated by depositions and degradation of these molecules during homeostasis, some diseases and injuries can disrupt this balancing process. Macromolecules in diseased ECM can be over-represented (upregulated) or reduced (downregulated) compared to levels in healthy tissue, meaning the microenvironment experienced by the cells drastically different in terms of the biochemical composition and in turn, mechanical properties. For example, major components of the microenvironment of the liver are collagen I, II, and IV, laminin, and elastin. During hepatic fibrosis downregulation of elastin is observed alongside an increase in liver stiffness as the disease progresses.

    Similarly, with regards to cancer it is known that most solid tumours are stiffer  than normal tissue, indeed breast cancer is usually screened by detecting hard lumps in the breast. This stiffening is generally accompanied by an increase in deposition of collagen I, II, III, V, and IX during tumour formation. These examples demonstrate that the different properties of the ECM are not independent; rather, they are intertwined. When the ECM stiffens under pathological conditions, its biomechanical properties change, and cells respond by exerting markedly different kinds of force. In addition, matrix stiffening also changes other ECM physical properties and, consequently, directly impacts how migrating cells interact with the ECM.

    Therefore, when developing cell-based models the ability to not only replicate the mechanical properties of the tissue of interest, but also being able to recapitulate the unbalanced ECM composition in diseased/injured tissue is important for providing a more physiologically relevant environment. This will enable amongst other things deeper investigation of the underlying mechanism of disease development, and more predictive pre-clinical assessment on the effects of drugs on both diseased and healthy tissue.

    Employing 3D cell culture matrices which incorporate cell adhesion peptides (CAPs) offers an excellent way to reproduce both healthy tissue- and diseases-specific ECM compositions in a synthetic system. Biogelx offers a range of peptide-based hydrogels which not only allow the stiffness of the final gels to be controlled to match the mechanical properties of specific tissues, but also incorporate biomimetic peptide sequences to mimic key ECM proteins, including fibronectin (RGD), Collagen (GFOGER) and Laminin (IKVAV and YIGSR). Whilst these products are available off the shelf, the simple modular nature of Biogelx technology means that it can be easily customised to your requirements e.g. we can work with you to develop gel formulations incorporating alternative CAPs to remodel a specific tissue microenvironment, or we can optimise the concentration and ratio of CAPs incorporated with your specific application in mind. So, if you are looking to develop more disease-relevant cell culture models, get in touch to discuss our hydrogel customisation service .

     

    References

    1. Forget et. al., Trends Biotechnol., 2018, 36, 4, 372-383
    2. Bataller & D. Brenner, J. Clin. Invest., 2005, 115, 209-218
    3. Lu et. al., J. Cell Biol., 2012, 196, 4, 395–406
    4. Yu et. al.,Trends Cell Biol.,2011, 21, 47–56

     

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  4. The advantages of peptide hydrogels over other 3D cell culture matrices.

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    Cell culture is an essential tool for the study of cell biology and preclinical biomedical research and has become a vital component of drug screening and toxicity testing in pharmacology research. Over recent years it has been widely acknowledged that 3D cell culture techniques can provide more physiologically-relevant results to more traditional 2D culture systems.

    Cell culture models utilising 3D matrices allow individual cells to maintain their normal morphology, allow complex cell-cell and cell-matrix interactions, and provides oxygen and nutrient gradients, thereby providing an environment which more closely mimics the natural ECM, promoting the creation of native architecture found in vivo. Such matrices often take the form of hydrogels.

    Hydrogels are water-swollen networks of crosslinked polymeric chains (up to 99% water) and have emerged as the most promising option for cell culture since they mimic salient elements of native ECMs and possess mechanics similar to those of many soft tissues.

    In this context, both natural and synthetic hydrogels have been investigated extensively for the encapsulation and culture of cells, with both classes providing their own set of advantages and limitations. To achieve the best of both worlds, researchers are turning their attention to synthetic peptide hydrogels as 3D cell culture matrices where a balance of biocompatibility and consistency are possible.

    Watch this webinar and learn:

    • How our synthetic peptide hydrogels can provide a more physiologically relevant environment in vitro.
    • How our 3D hydrogels can be tailored to control cell behaviour
    • The potential of synthetic peptide hydrogels in applications including cancer research, cell-based assays, and regenerative medicine.
    Presented by

    Robert Edward Schwartz, M.D., Ph.D.

    Assistant Professor of Medicine at the Sanford I. Weill Medical College of Cornell University and an Attending Physician, New York-Presbyterian Hospital Cornell campus

    Professor Matthew Dalby

    Professor of Cell Engineering (Institute of Molecular Cell and Systems Biology) at the University of Glasgow

    Mitch Scanlan

    Chief Executive Officer of Biogelx Limited, former Sales & Marketing Director of Sartorius Stedim BioOutsource, and former Head of Sales & Marketing at Millipore UK

  5. MODELLING IN VIVO CONDITIONS IN VITRO: 3D HYDROGEL SYSTEMS FOR BIOMEDICAL APPLICATIONS

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    The advantages of peptide hydrogels over other 3D cell culture matrices
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    Cell culture is an essential tool for the study of cell biology and preclinical biomedical research and has become a vital component of drug screening and toxicity testing in pharmacology research. Over recent years it has been widely acknowledged that 3D cell culture techniques can provide more physiologically-relevant results to more traditional 2D culture systems.

    Cell culture models utilising 3D matrices allow individual cells to maintain their normal morphology, allow complex cell-cell and cell-matrix interactions, and provides oxygen and nutrient gradients, thereby providing an environment which more closely mimics the natural ECM, promoting the creation of native architecture found in vivo. Such matrices often take the form of hydrogels.

    Hydrogels are water-swollen networks of crosslinked polymeric chains (up to 99% water) and have emerged as the most promising option for cell culture since they mimic salient elements of native ECMs and possess mechanics similar to those of many soft tissues.

    In this context, both natural and synthetic hydrogels have been investigated extensively for the encapsulation and culture of cells, with both classes providing their own set of advantages and limitations. To achieve the best of both worlds, researchers are turning their attention to synthetic peptide hydrogels as 3D cell culture matrices where a balance of biocompatibility and consistency are possible.

    Key Learning Objectives
    • How synthetic peptide hydrogels can provide a more physiologically relevant environment in vitro.
    • How synthetic peptide hydrogels can be tailored to control cell behaviour
    • Understand the advantages of these materials over other 3D cell culture matrices
    • The potential of synthetic peptide hydrogels in applications including cancer research, cell-based assays, and regenerative medicine.
    •  Case studies – The use of synthetic peptide hydrogels to direct stem cell differentiation, to improve cartilage phenotype in 3D culture, and their use in the 3D culture of hepatocytes for the development of an in vitro liver model.
    Register Now For Free >>
    Presented by

    Robert Edward Schwartz, M.D., Ph.D.

    Assistant Professor of Medicine at the Sanford I. Weill Medical College of Cornell University and an Attending Physician, New York-Presbyterian Hospital Cornell campus

    Dr. Schwartz is an active physician scientist focused on developing and building models of human liver disease in vitro. His interests include viral hepatitis, autoimmune causes of liver disease, Non-Alcoholic Fatty Liver Disease as well as metabolic causes of liver disease. He uses stem cell biology, hepatocyte biology and incorporates engineering techniques to better understand human liver disease with the goal to improve clinical therapy. >>

    Professor Matthew Dalby

    Professor of Cell Engineering (Institute of Molecular Cell and Systems Biology) at the University of Glasgow

    Prof. Dalby is a biologist interested in the way that mesenchymal stem cells from bone marrow interact with materials. His research interest includes  adult stem cell interactions with nanotopography, dynamic (cell responsive) surfaces, 3D hydrogels and growth factors organising interfaces; metabolomics for stem cells; and stem cell mechanotransduction. >>

    Mitch Scanlan

    Chief Executive Officer of Biogelx Limited, former Sales & Marketing Director of Sartorius Stedim BioOutsource, and former Head of Sales & Marketing at Millipore UK

    Mr. Scanlan is a business development expert who has successfully driven the commercialization of a range of technology and service companies within the life sciences sector. Mitch has worked for large multinationals, SME’s and start-ups including Millipore, Quintiles, Deloitte, Touche, Sartorius Stedim Biotech, Bioprocessors Corporation, and BioOutsource Limited. In his current role, Mitch works on the business transformation of a Scottish biomaterial SME called Biogelx.

    Register Now For Free >>