Search Results for '3d Bioprinting'

  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. Changing the future of medicine with 3D Bioprinting

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    The creation of artificial human tissues and organs may sound like a futuristic dream, but it is happening right now. Research institutes and hospitals around the globe have been working on bioprinting applications, which are providing new options for treatment and scientific study. Potentially, 3d bioprinting will be the next big thing in health care and personalised medicine.

    The idea of printing human organs, has its origins  in the invention of stereolithography in 1983. This special type of 3D printing relied on a laser to solidify a polymer material extruded from a nozzle. However, the material used in this process was not robust enough to create a long-lasting structure. By the early 1990s, the next generation of materials was introduced. Called nanocomposites, they were blends of plastics and powdered metals. These materials were more durable. They made possible the scientist to produce longer lasting end-products.

    It did not take long for medical researchers to notice the protentional of such materials and 3d printing technology in clinical application. In 1999, scientists at the Wake Forest Institute for Regenerative Medicine used a 3D printer to build a synthetic scaffold of a human bladder. They then coated the scaffold with cells taken from their patients and successfully grew working organs. This set the stage for true bioprinting. In 2002, scientists printed a miniature functional kidney capable of filtering blood and producing urine in an animal model. And in 2010,Organovo printed the first blood vessel. Today, 3d bioprinting companies like Cellink, Allevi , Regemat or SunP are focusing on printer and living inks development to provide future opportunities for complex organ printing.

    Within bioprinting, there are three main technologies, namely inkjet, extrusion, and laser-assisted printing. Inkjet printers possess a print-head that generates a pressure pulse (either thermally or acoustically) that forces droplets from the nozzle. Laser-assisted printers use pressure generated by a laser to propel cell-containing material from an absorbing substrate onto a collect substrate. Finally, and most commonly used, are extrusion printers that use pneumatic or mechanical piston/screw dispensing systems to extrude continuous beads of bio-ink.

    There are also different biomaterials which are reported as bioinks for 3D bioprinting. They are the Agarose-based, Alginate-based, Collagen-based, Hyaluonic acid-based, Fibrin-based, Cellulose-based, Silk-based and Synthetic biomaterials. Each class of bioink has pros and cons, however, they have a common requirement for control of mechanical and biological properties of the printable material.In terms of mechanical control, it is imperative that the bioink forms a microstructure which mimics that of the cell’s native environment. As well as a familiar architecture, the gel stiffness and porosity should be matched to that found in vivo so as to support cell growth, signalling, and proliferation. Ideally, the bioink will exhibit shear-thinning behaviour, as this will reduce the stress exerted on the cells during the printing process, which most commonly involves extrusion of the bioink through a narrow print-head. In order to assure biocompatibility, the raw materials used for the production of the bioink should not be cytotoxic to the cells in question, nor elicit an immune or inflammatory response.

    Using a combination of the right printing process and bioink, researchers have already been printing bone and skin tissues in the labs. Whilst work towards the bioprinting of more complex internal organs, such as the liver, is happening today in research labs all across the world,  it is anticipated that  fully functioning lab grown versions of these are still at least 10 years away, possibly more.

     

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  3. Novel 3D bioprinting method for creating ligaments and tendons from a patient’s own cells

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    Dr Robby Bowles and his team at the University of Utah have developed a 3D bioprinting method that allows them to lay down human cells in a controlled manner to produce human musculoskeletal tissue.

    Ligaments and tendons are both made up of fibrous connective tissue. Ligaments appear as crisscross bands that attach bone to bone and help stabilize joints. Tendons, located at each end of a muscle, attach muscle to bone. Their injury is often the result of habitual movements and can cause constant pain and body mechanics issues for the sufferer. Whilst current treatments, can include the replacement of these tissues using tissue harvested from another part of the patient’s body, often these samples do not meet the requirements  Furthermore, the treatment requires a long recovery period, and there is the risk of an unsuccessful outcome in many cases.

    Dr Bowles, assisstant professor of biomedical engineering, and his team have developed a novel 3D bioprinting technology capable of mimicking the complex cell gradients and transitions characteristic of musculoskeletal tissues, allowing the development of long-term solutions for patients with ligaments or tendons issues. Bowles’s technology is based on stem cells taken from the patients’ own body fat. These cells are printed on a layer of hydrogel in highly controlled manner to form a tendon or ligament. Then they grow in vitro before implanting them in a patient. This treatment would improve recovery outcomes since it would eliminate the need for tissue-replacement surgeries. “It will allow patients to receive replacement tissues without additional surgeries and without having to harvest tissue from other sites, which has its own source of problems,” said Bowles in a University of Utah press release.

    3D bioprinting ligaments or tendons is an extremely complicated process because they are made up of different cells in complex patterns. “For example, cells that make up the tendon or ligament must then gradually shift to bone cells, so the tissue can attach to the bone,” explained Dr Bowles. To provide resolution for this issue, Dr Bowles and his team have developed a unique printhead which allows them to create a pattern and organizations of cells. “It allows us to very specifically put cells where we want them,” said Bowles. The technology currently is designed for creating ligaments, tendons and spinal discs, but “it literally could be used for any type of tissue engineering application, or it could be applied to the 3D printing of whole organs”. Bowles believes that the novel printhead could be compatible with any kind of 3D bioprinter in the future.

    More information:

    Robby Bowles assistant professor of bioengineering
    Email: robert.bowles@utah.edu

    Source:

    D. Ede, N. Davidoff, A. Blitch, N.Farhang, and R. D. Bowles, TISSUE ENGINEERING: Part C, 2018,24, 9, 546 The University of Utah, Press release (Oct 2018): https://unews.utah.edu/the-fine-print/

     

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  4. Challenges of 3D bioprinting

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    Despite the successful studies and reported outstanding research efforts, the goal of 3D bioprinted organs has yet to be accomplished and there are several challenges which must be overcome. 

    1. Bioprinter technology

    Bioprinter technology needs to increase resolution and speed and should be compatible with a wide spectrum of biocompatible materials. Higher resolution will enable better interaction and control in the 3D microenvironment. Speeding up could build the opportunity to reach a commercially acceptable level and allow the process to be scaled up. 

    2. Biomaterials

    Biomaterials are undoubtedly the primary limitation of this technology. Today, we are limited to several biocompatible synthetic and natural bio-inks. Synthetic materials provide good mechanical strength and can mimic naturally-derived materials, which are particularly adept at promoting cell attachment, proliferation, and differentiation. 

    3. Choice of the cell source

    The choice of cell source also determines the success of the printed construct. Stem cells have the ability to differentiate into multiple different cell types and can build different tissues. Hence, their differentiation and interaction with the scaffold material are essential.

    4.  Vasculature of the printed construct

    Another fundamental issue is the vasculature of the printed construct. In vivo 3D tissue is constantly fed by oxygen and nutrients. If the tissue is constructed using a bioprinter, then it also needs a vascular system. Diffusion by itself will only work up to 150-micrometer thickness. Beyond this thickness, the tissue will not develop properly.

    These challenges will need to be addressed down this novel technology becomes fully operational and effective.  

     

    Sources: 

    Li, Jipeng et al. “Recent advances in bioprinting techniques: approaches, applications, and future prospects.” Journal of Translational Medicine (2016)

    Zhang, B., Luo, Y., Ma, L. et al. “3D bioprinting: an emerging technology full of opportunities and challenges“ Bio-design and Manufacturing (2018) 

    Veysi Malkoc “Challenges and the future of 3D bioprinting” Journal of Biomedical Imaging and Bioengineering (2018)

     

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  5. How to minimise cell damage during 3D Bioprinting

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    5 considerations to improve the biocompatibility of the 3D fabrication process

    Three-dimensional (3D) Bioprinting is a novel and promising technology, which may help to address the serious problem of human organ shortage in health care. Nowadays, 3D bioprinting is successfully used in many areas including tissue engineering and regenerative medicine, where it has allowed researchers to print complex structures such as a blood vessel, heart valves, bone, cartilage, kidneys, skin, nerves, and other tissues. 

    3D Bioprinting differs from other forms of 3D cell culture and requires the user to control several factors which are relevant to the printing process, which may place extra strain on the cells used for printing. 

    1.    Material properties

    3D Bioprinting technology uses biomaterials to mimic the extracellular matrix (ECM), which promotes cell adhesion, growth, proliferation, migration, and differentiation. These materials should support cell metabolism and provide a similar environment to that which is found in vivo. The biomaterials used should have excellent biocompatibility and tunable mechanical strength. Hydrogels are promising materials for this application, as they can be optimised to meet both of these requirements.

    2.    Scaffold Structure

    3D Bioprinting is aiming to fabricate organs with a high degree of similarity not only in shape but also in functionality with the human body. Therefore, the biocompatibility of biomaterials is the first parameter to be considered when fabricating scaffolds. The biological scaffold must simultaneously support the growth of different cell types, which may require specific mechanical properties, chemical gradients, cell populations, and geometric structures. The ideal material must have appropriate hydrophilicity, pH neutrality, and degradability. It needs to be biocompatible and mechanically stable. The cells are usually encapsulated in biodegradable hydrogels that mimic a tissue-like environment for building bioprinted ink. Hydrogels can be tuned to protect the cell contained within from the shear force generated in the printing process and maintain their bio-functions, such as the self-renewal ability and multi-lineage differentiation potency of stem cells.

    3.    Environmental control

    The external factors such as temperature and humidity are also important factors, as they can affect cell growth and proliferation. Some research show that the survival rate of cells is best at a temperature between 29 and 31 degrees and with humidity levels maintained at 65-85%. 

    4.    Printing precision

    In 3D bioprinting, a long-term goal is to achieve controlled single cell deposition. Especially for complex multi-cellular organs, single-cell control can simulate the structure of the human body to closely mimic human organs. Unfortunately, existing bioprinting technologies cannot yet achieve single-cell control. Improving the accuracy of the printers, coupled with a reasonable control algorithm is an important way to enhance the function of the fabricated tissues and organs.

    5.    Sterile conditions

    One of the key drivers of 3D bioprinting technology is to reproduce human organs for use in clinical transplantation. The printing process and final printed organs must, therefore, be sterile to eliminate the risk of infections. If the 3D printing process is time-consuming, the possibility of contamination is increased, and therefore decreasing printing time is a way to optimise 3D Bioprinting for this purpose.

     

    Sources: 

    Li, Jipeng et al. “Recent advances in bioprinting techniques: approaches, applications, and future prospects.” Journal of Translational Medicine (2016)

    Zhang, B., Luo, Y., Ma, L. et al. “3D bioprinting: an emerging technology full of opportunities and challenges“ Bio-design and Manufacturing (2018)

     

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