What is the role of Bioprinted Tissue Models in the development of drugs for COVID-19?

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A lot of the advances in additive manufacturing technology along with progress in material chemistry and tissue engineering techniques have led to the explosion of 3D bioprinting in recent years, which is largely due to advances in additive manufacturing technology. The key ingredients that make up the complex bioprinted structures are hydrogel-based biomaterials, often referred to as “bioinks,” and a cellular component that provides the building blocks to create 3D printed biological tissue from scratch. It is evident that the choice of cell source, proteins and other biological ingredients is largely determined by the application for which they are intended. I will only focus on the desire to create bioprinted tissue for the purpose of clinical translation in this blog post.

 

Models of human tissue that can be printed using bioprinting

There was a lack of predictive in vitro systems and animal models that could be used for testing the efficacy and safety of new drugs, which contributed to the emergence of bioprinted three-dimensional (3D) tissue models for drug discovery and development. Thankfully, as bioprinting tools have become more advanced and our knowledge-base continues to increase, the sophistication, precision, and complexity of today’s bioprinted tissue models are moving towards a reality – an ex vivo representative in vivo system.

Let’s take a moment to highlight recent developments related to bioprinting, including ones that are aimed at finding a cure for COVID-19.

 

A tissue model for COVID-19 has been developed

Model of lung tissue

The company Viscient Biosciences announced last week that they would utilize the company’s unique approach to bioprinting and develop a lung tissue model to screen drugs against the COVID-19 virus. Dr. Keith Murphy, CEO of Viscient, was interviewed by Laura Elizabeth Lansdowne from Technology Networks to provide an overview of the company’s work. It is Keith’s belief that bioprinting has the potential to be an invaluable tool for researchers in diseases involving multiple cellular interactions, in order to help them to develop improved disease models that will help them to uncover new drug targets.

The company has done this for NAFLD (nonalcoholic fatty liver disease) / NASH (nonalcoholic steatohepatitis) by modeling the disease in vitro, identifying novel gene targets through this process, and developing drugs that modulate these gene targets in order to advance medicinal chemistry. Viscient plans to construct a 3D human lung model that can be used to study viral diseases using a similar approach and building upon the success and knowledge gained from its work in NAFLD/NASH.

 

Model of the respiratory epithelium

In a recent announcement, Korean bioprinting startup CLECELL announced that they had bioprinted a respiratory epithelium model that can be used to test viruses such as SARS-CoV-2 in the future. As a result of a request from a Harvard Medical School neurosurgeon, Dr. Choi-Fong Cho who was looking for an in vitro testbed that could be used in the development of a vaccine against this highly infectious virus, this study was motivated. It is imperative to note that CLECELL has developed its own proprietary bioprinting technology, which includes a 15-channel multi-channel system, which is capable of printing low, medium, and high viscosity materials. Presently, the company is focused on developing artificial tissues such as skin in order to mimic the human body.

At this point, these are the only two announcements made on the development of a tissue disease model for COVID-19 that have been released. However, it will not be surprising if more announcements are made in the weeks to come.

NCATS 3-D Tissue Bioprinting Program

Aside from these recent developments, it is worth highlighting on-going work in the 3-D Tissue Bioprinting program at the National Center for Advancing Translational Sciences (NCATS). This program was initiated in 2016 funded by the Cures Acceleration Network and initially started out as a research collaboration between the National Institutes of Health (NIH) and San Diego based company Organovo. With the funding support, this group was able to expand their core facilities and imaging capabilities to support on-going research. Additional pilot programs including bioprinting of tissue models to study ovarian cancer metastasis and cardiovascular disease were initiated. The organizers continue to seek active collaboration in the development of bioprinted skin tissue and breast cancer metastasis models in a vascularized lung.

On-going work

In other areas of development, neurological disease modeling remains as one of the most highly pursued and challenging areas of research as the central nervous system bears the most complex tissue architecture in our body. Recently, a group of scientists from Utrecht University published a comprehensive review covering the current state in bioprinting of neural cells and tissues, including technology and bioink limitations, and a discussion around existing challenges in the field.

 

Some key takeaways from this review: With respect to extrusion or droplet based bioprinting lies in the dilemma of bioink selection versus print fidelity. Neural cells prefer softer materials and hydrogel which unfortunately do not generally have good print fidelity. Use of light based bioprinting techniques for neural cell printing have not been as extensive – some groups have used laser-induced forward transfer (LIFT) to bioprint human induced pluripotent stem cells. Looking ahead, researchers need to figure out how to combine the knowledge of material science, brain and neural cell biology, and electrophysiology supported by biofabrication techniques to orchestrate appropriate physiological guidances including mechanical cues and electrical stimulation to generate neuronal systems that capture the complexity of the brain.

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