Kenny Dalgarno, of Newcastle University, discusses his work on 3D printing of cells and how it’s helping to promote tissue regeneration
The ability to use 3D printing to create customised orthopaedic implants is now commercial reality, but combining these implants with cells to promote tissue regeneration remains a challenge.
Researchers at the EPSRC Centre for Innovative Manufacturing in Medical Devices (MeDe Innovation) are developing new techniques that will allow synthetic and biological materials to be processed alongside each other, reliably and at speed.
These approaches offer a glimpse into the future of orthopaedic implant surgery where customised implants are rapidly manufactured and then populated with the patient’s own cells, all during a single surgical procedure.
Central to success will be technologies such as our new 3D printing process, developed as part of the MeDe Innovation programme by researchers at Newcastle University. Called Reactive Jet Impingement, or ReJI, the process allows for cells distributed in a gel to be combined with structural implants. Depositing these gels onto the implant material creates a cell-filled layer at the interface between the implant and the native tissue.
The JeJI process works by jetting droplets of gel pre-cursors at one another, which then react in mid-air before dropping onto a substrate. The new process is quicker and allows for greater cell densities than syringe- or extrusion-based approaches to bioprinting, making it an excellent approach for in-clinic manufacture.
Another advantage is that the gel precursors are much easier to process than finished gels. By having the gel-forming reaction at a late stage, it allows printing to be faster and more reliable. We have printed cells in fibrin gels by mixing thrombin and fibrinogen through two impinging jet flows. It has also been possible to print cells in alginate gels, and in hybrid collagen gels, and we have been able to show that cell-filled gels printed in this way have high viability.
Our work has also led to the manufacture of a multiple jet head that is capable of printing four different materials at once. This provides new levels of control over the kinds of hydrogel structures that can be produced. By varying the gel formation from point to point, for example, it becomes possible to vary the stiffness of the gel.
These techniques could prove useful in a clinical setting where it might be desirable to have a stiffer gel in some areas to provide mechanical cushioning and a softer gel in others for faster release of cells to support integration.
A patent application has now been filed around the Reactive Jet Impingement technology and the methods for controlling the process. This is the first stage towards commercialisation of this new 3D printing process.
Technologies like these are central to making progress in one of MeDe Innovation’s key research themes: “Manufacture at the point of need”. Our aim is to develop processes that are minimally invasive, take place within a single surgical procedure, and can effectively deliver bioactive materials.
Printing cell cultures offers exciting possibilities for treating musculoskeletal disease and injury – but our work has also opened up new opportunities for printing cell co-cultures that can be used for drug testing or disease modelling. With funding from the National Centre for the Replacement, Refinement and Reduction of Animals in Research, we have begun a new collaboration with Alcyomics, a pre-clinical drug testing company, and the Universities of York, Nottingham and Leeds. Our aim is to develop a lab-on-a-chip device for in vitro testing of new drugs for osteoarthritis. By combining several cell types, such as chondrocytes, osteoblasts, synovial cells and immune cells, we hope to model the disease and test treatments without the need for animal models.
Kenny Dalgarno, is Sir James Woodeson Professor of Manufacturing Engineering at Newcastle University, and Deputy Director of the EPSRC Centre for Innovative Manufacture in Medical Devices (http://mede-innovation.ac.uk).