Category Archive: 3D Cell Culture

  1. Making Synthetic Hydrogels Better Extracellular Matrix Mimics

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    Extracellular matrix (ECM) mimics are used in a wide range of applications in cell culture, tissue engineering, regenerative medicine and the fast-growing market of bioprinting. Like the ECM itself, which is the non-cellular component present within all tissues and organs, they provide structural, biological and mechanical support which allows cells to survive, grow, migrate and differentiate and help maintain normal homeostasis. Often such ECM mimics come the form of hydrogels, and can be either naturally-derived or synthetic, with both having theirs benefits.

    Naturally-derived materials have inherent biological properties which can more closely mimic the in vivo cell environment, often providing cell adhesion sites and great biocompatibility for cells. Hydrogel materials such as collagen or the complex protein mixture Matrigel are widely used in research, and have allowed the generation of a multitude of invaluable cell culture data as a result. There can be drawbacks associated with the use of these naturally-derived ECM mimics however, as batch to batch consistency is renowned for being variable which can be troublesome for sensitive or long term experiments. Often, temperature dependency/sensitivity of these materials can cause practical issues for users e.g. having to chill equipment and work on ice to maintain an optimum temperature can impart added complexities to experimental procedures.

    Synthetic ECM mimics are increasingly being used as they can provide solutions to some of the issues that naturally-derived materials pose. The main benefit of synthetic hydrogels is consistency. There should be no batch to batch variations as they are produced using known quantities, optimised procedure, and generally the chemistry of the polymer does not change unless required. As they are synthetic, there are no components from animal-derived sources which can be an important factor for cell culture and tissue engineering research with the ultimate aim of clinical applicability. Synthetic ECM mimics also have the advantage of being carefully manipulated to suit an individual application. This can be done by tailoring the physical properties, but also by controlling the chemical structure of the materials. For example, the ability to incorporate biomimetic peptide sequences such as the RGD motif from fibronectin , or GFOGER from collagen at carefully controlled concentrations can be crucial for many synthetic matrices to provide good cell recognition sites. Indeed, with the addition of such components at similar concentrations to those found in vivo, synthetic ECM mimics have the potential to rival their naturally derived counterparts.

    The ability to combine the benefits of both naturally-derived and synthetic hydrogel matrices could provide a product which would mimic the biological, mechanical and structural support found in native ECMs, but with batch to batch consistency, easy handling and the ability to manipulate. A totally synthetic ECM containing a combination of biomimetic peptides sequences would provide the user with a more consistent product, whilst still retaining biologically active sites found in protein-based matrices.

    Biogelx currently provides 5 off the shelf synthetic hydrogel products including 4 containing biomimetic peptide sequences from ECM proteins fibronectin, laminin, and collagen  (RGD, IKVAV, YIGSR and GFOGER respectively), each demonstrating benefits to different cell types. We are excited to share that we have been developing our next generation of peptide hydrogel product! In this single product we combine such biomimetic sequences in ratios which match the protein composition of a highly effective naturally-derived hydrogel product, and thus more closely mimic the natural ECM. With this new product, we hope to bring users the best of both worlds, providing the biological relevance of naturally-derived materials with the consistency of a synthetic hydrogel. Watch this space for more info and details on the lauch!

     

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  2. 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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  3. Biogelx peptide hydrogels: Bio-inspired materials for 3D cell culture and bioprinting

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    Listen to our 25-minute presentation, and explore Biogelx core technology with Dr. Chris Allan, Development Scientist.

    At Biogelx, we are helping people who work in translational science, drug discovery and tissue engineering by making in vitro cell cultures more in vivo. We do this through manufacturing and supplying 3D cell culture materials that can be tuned to specific tissues, and synthetic bio-inks that are reproducible and easy to handle. Our portfolio of biomaterials is comprised of synthetic peptide hydrogels that mimic the extracellular-matrix to support cell growth. In addition, the chemical and physical properties of our biomaterials can be precisely tuned to replicate the characteristics of specific tissues so that the cells experience and engage with a realistic 3D environment.

    Key Learning Objectives:

    • The advantages of Biogelx hydrogel technology
    • Biocompatibility is key: growing a wide range of cell types
    • Printing with peptide hydrogels: A case study of synthetic bio-ink development
    • Here to support you: Bio-ink formulation service

    Do you want to learn more? Watch our recent webinar on ‘The advantage of peptide hydrogels over other 3D cell culture matrices’. Click on the link below!

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

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

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    Watch the video now!

    Try Biogelx 3D Hydrogel Systems! Buy a Discovery Kit!

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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. Advanced in vitro models analysis – TEDD Annual Meeting 2018

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    During the past two decades, we have witnessed significant scientific and technical advances in the fields of drug discovery and translational medicine along with advances in predictive in vitro model systems. As of now, microfabrication techniques and tissue engineering have enabled the development of a wide range of 3D cell culture technologies, including multicellular spheroids, organoids, scaffolds, hydrogels, organs-on-chips, and 3D bioprinting, each with its own advantages and disadvantages. 3D culture models have been penetrating into the early drug discovery process, starting from disease modeling to target identification and validation, screening, lead selection, efficacy, and safety assessment.

    This year’s TEDD Annual Meeting brings together experts from diverse fields with a shared interest in advanced 3D models. The idea is to help to foster collaborations between 3D cell culture developers, and experts in advanced analysis methods: microscopy, sensors, data modelling, and high-throughput screening. Several companies will exhibit during our famously long lunch break at the Greenhouse, where we have the opportunity to interact. Join us for this meeting to celebrate another fruitful collaboration year with the new perspectives ahead.

    Exhibitors:
    Thermo Fisher Scientific – Biogelx – Promega – Imactiv-3D – ABC Biopply ag – StemCell Technology – Hit Discovery – Bachem – Binder – Greiner Bio-One GmbH – Cellbox Solutions – LOT-QuantumDesign – Bio-techne – Optics11 – Biotek

    Program: click here

     

     

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