Bioprinting and 

COVID-19

Our brief on how the technology of 3D Bioprinting is changing the world and on how its aiding in the fight against COVID-19

24th August 2020

Authors – Anubha Mehra and Sairam Reddy

3D Bioprinting is a revolutionary technology that has created an immense impact in the field of medicine and healthcare. It has enabled us to mimic the natural tissue microenvironment into an in-house printed three-dimensional tissue model. This groundbreaking technology has enabled researchers to expand the horizon of their multidisciplinary research areas.

Currently, the focus is on the development of application-specific bioinks and new biomaterials, which play a crucial step for the advancements in bioprinting tissues and organs for clinical use.

Wake Forest Institute of Regenerative Medicine

A spatial scaffold was used to build the world's first synthetic organ.
The scaffold was colonised with the patient's cells to rule out the chances of organ rejection. Ten years after implantation, the patient did not show any dangerous complications.
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Organovo

the first scaffold-free vascular constructs were developed by Organovo.
By 2010, skin printing and injection of hepatocytes into collagen was also possible. Over the years, Organovo had effectively established itself as a leader in bioprinting technology.
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Tel Aviv University

A team of scientists from Israel printed a mini-heart, that was capable of contraction and had blood vessels.
The print, although the size of a rabbit's heart, had its anatomical arrangement and biochemical functions preserved. This 3D bioprinted heart proves that printing fully functional organs is one day plausible, although it still has a long way.
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Bioprinting finds its utility in the fields of tissue engineering and regenerative medicine, transplantation, drug screening, and cancer research. Tissue engineering using bioprinting technology is the most recognised application. Bioprinters are used to manufacture scaffolds and fabricate anatomically correct patient-specific tissue constructs. In-vitro bioprinted tissues such as skin, nerve and bone have been implanted on animals to evaluate their functionality, neovascularisation, and engraftment with the host.

Bioprinting for Organ Transplantation

Several bioprinted tissue types have been transplanted into animals to examine their functionality in a host. These studies have not been conducted on humans yet due to the lack of regulatory protocols. Eventually, given the time for maturity and appropriate regulatory protocols, we might be able to bioprint an entire functional organ.

Inclusion of blood vessels, lymphatic vessels and nerves that are capable of integrating with the patient’s systems, will allow the creation of fully functional transplantable organs like livers, kidneys, lungs and hearts.

Bioprinting for Drug and Toxicology Testing

Innoskin®, developed by Next Big Innovation Labs®, is an alternative to animal testing for cosmetic, chemical and agro-chemical testing applications.

Drug discovery involves testing a vast number of candidate molecules which, in turn, requires a substantial investment of money and resources. 3D bioprinted models can assist in testing the efficacy of the candidate drugs as they closely mimic the native tissue environment. Bioprinted tissues can be constrained for their dimension and microarchitecture, high-throughput capability, co-culture ability, and possess low-risk of cross-contamination. 

Cosmetics, Chemical, and agribusiness are required to provide data on the efficacy and safety of their formulations or product on consumers. Bioprinted tissue models offer more effective results than poorly predictive animal models or poorly constructed 3D models that are built using the traditional biotech approach.

Bioprinting tissue models for cancer research

Two-dimensional tumour models lack the cell to cell and cell to matrix interactions that are present in 3D models as 2D models do not precisely mimic the native physiological environment. Bioprinting mimics the complicated cancer microenvironment by accurately situating various cell types and even microcapillaries. This approach will help the study of cancer as bioprinting can also aid in developing patient specific organ-on-a-chip platforms for personalised testing and develop much more precise research data.

3D Bioprinting in the battle against SARS-CoV-2

Over the last few months many Startups, Biotech, Engineering and 3D printing companies have launched initiatives to fight against the Pandemic by providing the necessary PPE’s kits, Faceshields, UV boxes, Antibodies, respiratory support apparatus, etc.

As hundreds of millions become infected, 3D bioprinting plays a crucial role in the pursuit of a cure for the novel coronavirus. Currently, bioprinting researchers are developing 3D Bioprinted Human micro-tissues, which are then infected with SARS-CoV-2. This allows them to study the disease progression in a tissue setup that closely mimics the native tissue micro-environment and physiology. The novel coronavirus is still being studied globally and we still do not understand much about it. Understanding the kinetics of the viral infection and disease progression better will aid in faster and effective vaccine development.

Many Biotech companies and Researchers have already started developing bioprinted human tissues that are being tested with new methods or treatments. Below are examples of a few of them.

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Viscient Bioscience LLC has been working in the area of 3D Bioprinting for a long time. They have been involved in bioprinting of human liver tissues from diseased patients to study pathological tendencies. They are currently working on bioprinting lung tissues to support viral infectivity research. These tissues will help in developing effective therapy or treatment against the SARS-CoV-2.

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Researchers from 3D Bioprinting Solutions are using their proprietary method to build spherical cell aggregates or spheroids (created by using bioprinting). The spheroids are then infected with SARS-CoV-2 and used to test various formulations. The advantage here is the usage of spatial cell aggregates, whose reaction may differ from traditional two-dimensional cell substrates. They believe that testing new formulations on three-dimensional models gives more reliable results, comparable to the native tissue of the human body.

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CLECELL is mainly focused on research and development of artificial tissue by using their proprietary 3D bioprinting technology. The research team from CLECELL has been working on building respiratory epithelium models (epithelial cells are the first to get exposed to the virus). CLECELL also stated that the respiratory epithelium model is expected to become a test bed not only for SARS-CoV-2 but also for research of mechanisms of other viruses.

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The Wake Forest Institute for Regenerative Medicine is creating tiny replicas of human organs such as miniature lungs and Colons (as these two organs are most affected by SARS-CoV-2) to test drugs for COVID-19.

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The Wistar Insititute  has collaborated with Allevi Inc. on a 3D bioprinting project to advance COVID-19 Research. Allevi Inc will use its proprietary and patented 3D bioprinting platform to create three-dimensional lung models. Wistar scientists will use these models to study SARS-CoV-2.

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Research collaborators of CELLINK are using INKRECIBLE+ and BioX to bioprint an improved lung model to study SARS-CoV-2, using primary human lung fibroblast containing macrophage, air-liquid interface, and mechanical stimulation. The aim is to establish an infection model for SARS-CoV-2 and develop an RNAi strategy against the dealdly contagious virus.

With unemployment on the rise, people looking out for jobs are upskilling themselves and are working towards better and more stable futures for themselves. New age sectors, such as 3D Bioprinting, are currently providing researchers and students with an opportunity to amass niche tools that make them stand out in the sea of many. 3D Bioprinting provides new avenues for testing and development, as mentioned above. These are just a few of the many ways in which 3D Bioprinting is being deployed in the fight against COVID-19. With research and financial aid in this domain on the rise, employment opportunities in 3D Bioprinting is in an upward trend in a world where millions have lost their jobs in a span of months.

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Future of 3D Bioprinting

Bioprinting technology has gained enormous attention as a fabrication methodology for the production of 3D tissue structures that will play a crucial role in tissue engineering, regenerative medicine, transplantation, drug testing and clinical trials. As discussed earlier, 3D bioprinting is capable of producing living tissues, blood vessels and can generate patient-specific tissues for the development of personalised treatments. 3D bioprinted organs, when used for transplants, will comprise the patient’s own cells, this drastically reduces the chances for tissue rejection. There are many challenges yet to overcome to build complex tissues  that comprise of multiple cell types in a confined microarchitecture. 

Most countries are implementing a ban on animal testing. New formulations are tested on animals to study the efficacy and safety of formulations. Diseases that are induced in animals are never identical to human beings. NIH states 95% of the drugs that test safe in animals fail during human trials.

Although bioprinting transplantable organs is going to take a while for us to achieve, 3D bioprinting’s first call to action is the fight against animal testing. While 3D Bioprinting researchers, globally, are pushing the envelope towards fully transplantable organs, the immediate future for the technology lies in labs where bioprinting can be implemented to develop more standardised and accurate tissue testing platforms.

Author - Anubha Mehra

Anubha handles marketing, IP and regulatory activities within Next Big Innovation Labs. She is an experienced marketeer who focusses on building customer oriented marketing strategies for biotech led enterprises. Working on the IP and regulatory aspects of NBIL, Anubha understands the various nuances involved in building and marketing patentable and innovative products.

Author - Sairam Reddy Chinthamreddy

Sai is a senior project engineer at Next Big Innovation Labs. Prior to join NBIL, Sai has worked on key engineering and 3D printing projects for Merck KGaA at Germany. His experience working with 3D Printers and Bioprinters over the years has allowed him to explore the varied applications of the technology across industries.