How can Bioprinted Tissue Models help develop drugs for COVID-19?

Bioprinting Tissue Models

The advent of bioprinted three-dimensional (3D) tissue models for drug discovery and development has been propelled by the lack of predictive in vitro systems and animal models for testing efficacy and safety of new drugs. Fortunately, as bioprinting tools have become more advanced and our knowledge-base continues to increase, the level of sophistication, precision and complexity of today's bioprinted tissue models are moving closer toward a reality - an in vivo like system that is representative of the human body ex vivo.

Tissue models: Cancer progression on the skin

Given how everything has been evolving and revolving around COVID-19, let's take a moment to highlight recent developments specific to bioprinting including ones that are targeted toward finding a solution for COVID-19.

Tissue Models for COVID-19

Lung Tissue Model

Last week, Viscient Biosciences announced that the company is leveraging their unique approach to bioprint and develop a lung tissue model to screen drugs against COVID-19. Dr. Keith Murphy, CEO of Viscient, was interviewed by Laura Elizabeth Lansdowne from Technology Networks to share their work. In diseases where multiple cellular interactions are involved, Keith believes that bioprinting can benefit us by helping researchers to create improved disease models to uncover novel 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 advancing medicinal chemistry by developing drugs that modulate these gene targets. Using a similar approach and building upon the success and knowledge gained from their work in NAFLD/NASH, Viscient plans to build a 3D human lung model that can be used to study viral infectivity - click here to read from this interview.

Respiratory Epithelium Model

Most recently, Korean bioprinting startup CLECELL announced it has bioprinted a respiratory epithelium model that can be used to test viruses including SARS-CoV-2 (read news). This work was motivated by a request from Harvard Medical School neurosurgeon, Dr. Choi-Fong Cho who was seeking to find a suitable in vitro testbed for developing a vaccine against this highly infectious virus. CLECELL has a proprietary bioprinting technology which includes a 15 multi-channel system that can support printing of low, medium and high viscosity materials. The company currently focuses on developing artificial tissue such as the skin.

So far, this has been the only two announcements made on the development of a tissue disease model for COVID-19, it will not be surprising to see more coming in the weeks ahead. So stay tuned.

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 model 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 biopriting of neural cells and tissues, including technology and bioink limitations, and a discussion around existing challenges in the field (click here to access this open-access article).

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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