Dr. Mark Ungrin

My primary research focus is in the area of micro-tissue / organoid engineering – that is, tissue engineering on the sub-millimetre scale. Many groups around the world are working on producing various clinically useful cell types from stem and progenitor cells. The next major challenge is in assembling these cells into something useful, so they can be delivered to the patient to treat disease, or used in research labs as new model systems to study tissue behaviour. The injection of single cell suspensions into a patient has proved challenging, as many cells die, or end up in inappropriate locations. Engineered microtissues have many advantages, in that they are still small enough to be introduced through the bore of a needle – thus avoiding the need for major surgery – but the introduced cells come with their own supportive micro-environment, functional connections to their neighbours, and are not subjected to the trauma of dissociation.

We collaborate with a number of groups in a wide range of organoid and tissue types in both academia and industry, and of the projects that are currently public, it is our work in the area of diabetes that is likely closest to the human clinic. In addition, we are currently pursuing a novel strategy for intervention in orphan diseases, with funding from the NFRF, and exploring various applications of synthetic biology tools to tissue and organoid engineering.

Beyond development and study of the microtissues and organoids themselves, we are also developing the next generations of my AggreWell organoid engineering platform, and understanding how cell manufacturing processes can be adapted to make scalable production economically sustainable. As a research tool, it has already had a significant international impact and is now one of the standard approaches for the large scale production of uniform size- and composition-controlled organoids across tissue types in both academia and industry. Among other examples this notably includes both 2021 papers reporting groundbreaking models of the early human embryo, as well as the preceding mouse models reported in 2018/2019. Current efforts are focused on establishing and validating microtissue / organoid production at scale for clinical applications, to provide a bridge for the large existing user base to translate their bench-scale findings to pre-clinical and clinical trials. Members of the group have received various recognitions for this work, including being chosen for Mitacs' 2019 Outstanding Innovation Award (Doug Kondro, in the PhD category) and my own naming as a University of Calgary PEAK Scholar.

We also have an interest in the use of 3D printing and other prototyping technologies to develop simulated body parts for medical training applications and veterinary prosthetics.

My group also has a long-term interest in research quality and reproducibility - critical factors for successful translation of any research to the human clinic - and the under-recognized role of basic factors such oxygen in introducing variability into culture systems (if you are working with cell culture in a context where oxygen levels are relevant, you should probably read this paper). This work has also been incorporated in the recently published Guidance document on Good Cell and Tissue Culture Practice 2.0 (GCCP 2.0), where I was a member of the Scientific Advisory Board.

Dr. Ungrin’s research program centers on the assembly of cells into tissues and organs – how it occurs in nature, and how it may be induced for the purposes of tissue engineering and regenerative medicine. Formerly employed at Merck prior to starting his academic career, his underlying philosophy is to identify areas where research is limited by available technology, develop the necessary tools and techniques, and then apply them to pursue avenues of research that would not otherwise be accessible.

An example is his widely-adopted "AggreWell" microscale tissue / organoid engineering platform, now sold internationally via a license to StemCell Technologies Inc. He continues to develop this platform to enable both high throughput screening of conditions as well as clinical-scale engineered tissue construct production. His group is currently applying it to the generation of large numbers of uniform, engineered pseudoislets for both research and clinical applications in diabetes (published as the cover article for the September 2018 issue of Diabetologia).

Dr. Ungrin also has a broad interest in enhancing the efficiency of scientific research in the biomedical area (the conversion of time and resources to knowledge and innovation), in addition to pursuing the integration of his tissue engineering platform with laboratory automation and Response Surface Methodology to enhance his own group's productivity, is working to develop tools that will enhance the research of the community as a whole (e.g. in-press publication at PLOS One on the need for better consideration and reporting of oxygenation conditions in mammalian tissue culture to ensure reproducibility). His group is assessing the integration of microtissues with bioprinting, and he has co-founded a company to explore the commercial potential of 3D printing in the human and veterinary medical areas, including both clinical and training applications.