THE PROBLEM
The culture of human cells in the laboratory traditionally uses simple flat surfaces (cell culture flasks, petri dishes, and multiwell plates). It is increasingly understood that this '2D cell culture' is not representative of the 3D environment that these cells experience in the body, with effects on their health, behaviour, and functions. 2D cell culture is non-physiological, and limits the validity of scientific investigations in which it is employed.
Additionally, tissue engineering requires human cells to be grown and assembled into complex 3D geometries in order to form replacement tissues or organs for the treatment of injury or disease.
A great need exists for materials that can support the culture of human cells in 3D for laboratory research and tissue engineering applications.
CONTEXT
3D cell culture is an emergent market in the pharmaceutical, medical, and biotechnology fields, driven by increased research in cancer, stem cell therapies, tissue engineering, and regenerative medicine, and adoption of alternatives to animal testing. This market is currently estimated to be worth ~$1.4 billion, growing to over $6.5 billion by 2022. Significant business opportunities exist and are indeed growing for new 3D cell culture technologies.
In pharmaceutical research, many drugs fail in development at the transition from lab culture to animal experiments. The lack of physiological relevance in current 2D cell culture systems contributes heavily to these failures. Using 3D cell culture systems in the laboratory will power more relevant investigations, improving drug development efficiency, and reducing costs.
In medicine, tissue engineering is set to revolutionise current treatment pathways, by allowing damaged tissues and organs to be regrown. 3D cell culture technologies are required to underpin this emergent field.
UNDERPINNING RESEARCH
Professor Frederik Claeyssens and Dr Sam Pashneh-Tala have developed two photocurable, polymer biomaterials as the basis for a 3D cell culture platform.
These materials, polycaprolactone-methacrylate (PCL-M) and poly(glycerol sebacate)-methacrylate (PGS-M), are both elastomeric, degradable under physiological conditions, and have mechanical properties that can be tailored (Young’s modulus from kPa to MPa range).
RESULTS
Using emulsion templating techniques, the photocurable polymers PCL-M and PGS-M were formed into highly porous structures suitable for supporting 3D cell culture. These 'scaffolds' are ~80% porous with pore sizes suitable for cell infiltration.
Critically, the emulsion templating technique, permits the porous polymer scaffolds to be fabricated in almost any shape, using casting or moulding processes followed by rapid photocuring. Simple disk structures can be produced for insertion into standard cell culture multiwell plates to enable 3D cell culture. More complicated 3D structures can be produced for use in tissue engineering.
Various tubular structures have been fabricated for use in growing tissue-engineered blood vessels. Where these structures had previously been limited to simple straight tubes, a variety of anatomically relevant designs are now possible, including bends, branches, and even valves.
IMPACT
The work has yielded a patent application in order to allow the commercial exploitation of the technology across the cell culture and tissue engineering fields.
This highly adaptable 3D cell culture platform has the potential to revolutionise laboratory research, providing more physiologically relevant investigations, and driving new discoveries.
In tissue engineering, the technology permits highly complex and even patient-matched scaffold designs, as has been proven in vascular applications. This will provide new treatment pathways based on replacing damaged tissues and allow for improved research platforms, reducing or replacing the use of animals.