How can bioprinting enable better drug discovery?
Stephanie Willerth , CEO, Axolotl Biosciences
Dr. Stephanie Willerth is a biomedical engineer, entrepreneur, and thought leader in 3D bioprinting and neural tissue engineering. As CEO of Axolotl Biosciences and a Full Professor at the University of Victoria, she leads innovations in personalized medicine through bioink development and human tissue models. Her work bridges academia and industry, bringing groundbreaking research into real-world healthcare applications.
Abstract:
3D bioprinting generates tissues on demand by using cell laden bioinks patterned structures based on specifications provided in a computer file. This field has progressed at a rapid rate and recent technological advances have enabled the generation of human tissue models with physiological properties that are suitable for applications, including drug screening and regenerative medicine.
1. How is 3D bioprinting reshaping traditional drug discovery models, particularly in reducing reliance on animal testing and 2D cell cultures?
Traditionally, drug screening has been performed in animal models – usually mice and rats – whose biology does not accurately reflect human physiology. This effect is particularly pronounced when screening potential drugs to treat neurodegenerative disease, which have a high failure rate when such drugs are evaluated in clinical trials. 3D bioprinting using human cells provides a more reproducible humanised system compared to animals and 2D models, given their 3D structure. These 3D bioprinted tissues also avoid some of the limitations of organoids by increasing reproducibility.
2. What recent technological advancements have significantly improved the physiological relevance of bioprinted human tissue models?
Recent efforts have demonstrated how complex tissue models containing multiple cell types can be produced in a high throughput fashion and then cultured for extended time to enable drug screening. 3D bioprinting can pattern multiple cell types into physiologically relevant, complex functional structures. Additionally, work has been on-going to incorporate components of the immune system in these 3D bioprinted models.
3. How do cell-laden bioinks influence the accuracy and reproducibility of drug screening outcomes?
Appropriate bioink design ensures that the cells maintain their viability and function post printing, which are important considerations when using them as a tool for drug screening.
4. In what ways can bioprinted tissues better mimic human organ complexity compared to existing in vitro models?
Bioprinting allows you to control the number and type of cells in a construct. Additionally, the additive manufacturing nature of the process enables the patterning of physiologically relevant structures, including vasculature – which is highly important when mimicking the properties of human organs. It also enables the study of how these cells behave and respond to drug treatment in a 3D structure similar to what they would encounter in an in vivo setting.
5. What are the key challenges in standardizing bioprinted tissue models for widespread adoption in pharmaceutical R&D?
3D bioprinting requires large numbers of cells to generate physiologically relevant tissue so scale up of cell production poses a challenge. Bioinks have also continued to evolve into more sophisticated materials for maintaining cell viability and function.
6. How can bioprinting accelerate early-stage drug screening and reduce time-to-market for new therapeutics?
Using 3D bioprinted human tissue models can enable more rapid screening of early stage drugs compared to traditional animal models. The movement away from animal models is in part due to a need to be able to screen drugs in a more relevant and rapid fashion. 3D bioprinting also lends itself to high throughput tissue production, providing an additional advantage over traditional animal models.
7. What role does computational design and digital modeling play in improving the precision of bioprinted structures?
The use of computer aided design enables the production of complex structures. Often the bioinks limit the precision of the structures produced during the bioprinted process.
8. How close are we to integrating bioprinted tissues into mainstream preclinical testing pipelines?
There has been uptake by Contract Research Organisations to use these models in preclinical testing pipelines.
9. What are the regulatory considerations and barriers for using bioprinted tissues in drug validation processes?
It will be necessary to validate these 3D bioprinted models to confirm their performance in comparison with their corresponding animal models and work with regulators to ensure that data obtained using these models can be used as the basis for clinical trials.
10. How can bioprinting contribute to personalized medicine and patient-specific drug testing?
Such 3D bioprinted tissues can be generated using cell lines derived from patients, including induced pluripotent stem cells (iPSCs). For example, our group has generated tissues from iPSCs taken from patients with Alzheimer's and Parkinson’s disease and these tissues do express disease relevant features.
11. What limitations still exist in replicating vascularisation and long-term tissue viability in bioprinted constructs?
Ensuring that the integrity of vessels and their function remains intact presents a big challenge in the field. Additionally, mimicking the properties of blood and fluid flow also pose a challenge when 3D bioprinting.
12. How are collaborations between biotech companies, pharmaceutical firms, and academic institutions driving innovation in this space?
There are numerous examples of collaborations between academic institutions and bioprinting companies. For example, my lab received one the first Aspect Biosystems RX1 bioprinters back in 2016 and we have several joint publications together. We have also used our Cellink bioprinter in combination with Axolotl Bioscience’s TissuePrint bioink to generate neural and skin tissues. The 3D bioprinting ecosystem is quite strong.
13. What cost-related challenges must be addressed to make bioprinting a scalable solution for drug discovery?
Both cells and bioink tend to be expensive so being able to make these components affordable to create a scalable solution for drug discovery.
14. Looking ahead, what breakthroughs are needed for bioprinting to fully transform the future of drug discovery?
Better bioink formulations for supporting the 3D bioprinting of complex tissues are necessary to drive this field forward. Additionally, production of more complex structures that fully replicate tissue and immune function found in humans in vivo would be a major breakthrough in the field.
