LONDON – GE Healthcare Life Sciences is bringing its heft to 3D bioprinting in an agreement with Advanced Solutions Life Science Inc. (ASLS), in which the partners aim to automate the production of quality-assured, vascularized tissues, for bone, soft tissue and organ replacements.
The first fruit of the partnership, a system integrating ASLS’s 3D bioprinting robot, Bioassemblybot, with GE’s IN Cell Analyzer high-throughput microscopy imaging and screening platform, is being unveiled at the joint meeting of the American Society of Cell Biology and the European Molecular Biology Organization, taking place in Washington this week.
Combining the two technologies is intended to get to the heart of the reproducibility problem in manufacturing with cells – of being able to show it is possible to deliver the same product, time after time.
While the longer-term aim is to manufacture replacement organs and tissues, most immediately the system will enable high-throughput screening of 3D-printed human tissue models in drug discovery.
Those 3D models will mimic the reaction of human tissue, providing a physiologically more relevant environment for drug testing than traditional 2D cell monoculture, according to Emmanuel Abate, general manager of Genomics and Cellular Research at GE. Printing multimaterial objects inside microwell plates will create 3D discovery and cytotoxic models “that more accurately reflect native biology and disease,” he said.
The IN Cell Analyzer can automatically track how the 3D tissues respond to chemical and biological challenges in real time and makes it possible to monitor response in fine detail.
Traditional 3D bioprinters are not designed to interoperate with high-throughput screening tools. The combination of the two technologies will allow cellular imaging information to feed back into the tissue design process, speeding the development of quality-assured assays.
“The biggest challenge in drug discovery is safety and effectiveness, and [the industry] has always had very poor models; they are either human cell 2D monolayers or animal models,” said Prachi Bogetto, segment leader, Diagnostics, GE Healthcare. New tools including organoids and 3D culturing systems appear to represent an advance, but Bogetto said, “Do we really know if they organize as a human [tissue] would?”
The combination of bioprinting with high-throughput microscopy will create more faithful mimics. “We can tell if it is a fair model, and we can do it very quickly. Artificial intelligence will help us recognize what is high quality. It sounds simple, but it is complex,” Bogetto told BioWorld.
While it is early days, the partners have developed some protocols for 3D human tissue models that will have guaranteed, consistent properties.
GE and ASLS had support from Biofab USA, a Department of Defense (DOD)-funded project, managed by the Advanced Regenerative Manufacturing Institute (ARMI) based in Manchester, N.H., in carrying out the work to integrate their products.
BiofabUSA is a public-private partnership between DOD and ARMI with a mission to make large-scale manufacturing of engineered tissues a reality. To do that, it is fostering development of methods for automating and monitoring production methods to ensure consistency and quality assurance of tissue identity, viability, functionality and efficacy.
In addition to its robot, Louisville, Ky.-based ASLS lays claim to technology for bioprinting small blood vessels, which it says self-assemble into functional capillary beds that deliver nutrients, oxygen and hormones, and remove waste, from the 3D tissue models.
“It’s well known the big challenge with bioprinting lies in how cells organize without a blood supply. They can’t survive and can’t grow,” Bogetto said. ASLS’s Angiomics technology “mimics angiogenesis and vascularization that you would see in vivo. For me, that is very exciting,” said Bogetto.
Researchers elsewhere are seeding tissue constructs with endothelial culture media to promote formation of capillaries. Another approach is to cut networks of vascular channels, or dissolve away the polymer matrix in which the cells are suspended, to create a route through which to perfuse oxygenated media.
The problem with those and other protocols for generating microvasculature has been to find ways to get them to self-assemble, rather than having to bioprint the vessels.
Jay Hoying, of ASLS, has devised a way to generate more realistic vasculature using adipose tissue. He discovered that microvasculature in the abdominal fat of mice spontaneously grows new vessels which self-assemble into a vascular bed that mimics the disorganized native structure.
When those vascular beds are placed into heart, liver, kidney and neural tissues, they go on to form vascular beds that are characteristic of the different tissues.
Printed cells with vascularization are the first step toward more complex biological structures.
While it is a starting point, Bogetto does not expect replacement organs to be a reality any time soon, pointing to the long time it took for gene and cell therapies to become a therapeutic and commercial reality.
There are parallels between bioprinting and cell and gene therapy in terms of GE’s business, with the company becoming a major supplier of tools and equipment for cell and gene therapy manufacturing, after making a strategic move into the field a decade ago.
Beyond tools for drug discovery, and automating and scaling up bioprinting, GE is looking to move research in replacement tissues and organs forward by developing replacement knee menisci. Bogetto said the company is in “active conversations” with scientists at the U.S. Department of Veterans Affairs, who are working in that area.