Tag Archive: 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. When is a bioink not a bioink?

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    With interest in bioprinting continuing to soar, research focussed on new strategies to develop “printable” materials (a previously identified progress-limiting factor in the field) has been ever-growing.  In recent years, the fabrication and assessment of new materials suitable for bioprinting has gained increasing attention, and with it the term “bioink” has become ubiquitous. As the number of bioinks on the market continues to grow an important question to consider is, does the term “bioink” mean the same thing to everyone?

    In a recent special issue of Biofabrication dedicated to bioinks, the increasingly divergent definition of the term “bioink” is precisely the focus of an interesting article from a group of world-leading experts in the fields of bioprinting and biomaterials. The authors give a brief history of the evolution of the term, from its origins in describing cells being printing on/in a hydrogel “biopaper”, to its more recent division into multiple subcategories including support bioinks and fugitive bioinks. They suggest that these more recent classifications are unnecessarily complicated and, highlight that these are derived from the definition of the associated biomaterials, which may not necessarily need to be considered when defining a bioink.

    The authors ultimately propose that bioinks should be defined as ‘a formulation of cells suitable for processing by an automated biofabrication technology that may also contain biologically active components and biomaterials.’ Thus, to call something a bioink it should contain cellsand should be considered distinct from (bio-)materials that can be printed and subsequently seeded with cells after printing, which the authors suggest should be termed “biomaterial inks.”

    Check out the full article here

    When is a bioink not a bioink?

     

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  4. 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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  5. Advances in Tissue Engineering: Bio-printed Ovaries

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    Several organs and various tissue types have been successfully printed since 3D bioprinting techniques were developed in the early 2000s. Among those are mouse ovaries, which were printed and implanted in mice by researchers from Northwestern University. The ovaries were functional, and mice could conceive and gave birth to offspring.

    The researchers, from Shah’s lab at Northwestern, bio-printed layers of gelatin to form small 3D microporous hydrogel scaffolds of varying pore geometry and seeded mouse follicles containing precursor ovaries into the scaffolds.

    The synthetic, follicle-seeded ovaries were implanted into female mice who had been surgically sterilized (their natural ovaries removed). These synthetic ovaries became highly vascularized in a few days, and after mating, the female mice bearing 3D-printed ovaries birthed healthy pups that were confirmed to have resulted from an egg ovulated from the synthetic ovary. The litters, however, were smaller than average (1-2 vs. 6-8 pups).

    This study opened up the possibility of restoring reproductive health and fertility to cancer patients who have been sterilized by chemotherapy treatment and represented an important advance in the applications of tissue bioengineering to the reproductive system.

    The results were published in Nature Communications; you can read the article here.

     

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