In the summer of 2020, a biochemist, a software consultant and a chartered accountant form a biotechnology company that is fast becoming a global market leader in biofabrication.
With an initial focus on 3D cell culture, CEO Jordan Copner concludes that current offerings on the market are of poor quality and sets about developing better scaffolds for biotechnological research.
He has an idea, but to realise his goal he needs a bespoke CAD modelling software. Development of an initial basic CAD modelling software is undertaken to enable the development of 3D Cell Culture Scaffold models, with the creation of these model layers based on rectangular construct primitives that realise the required 3D model on subsequent assembly of the layers.
“Thus,” Jordan tells TCT, “Graphical Rectangular Actual Positioning Encoding (GRAPE) modelling software is born.”
The birth of GRAPE is seen as the key enabler in Copner Biotech’s journey so far. It allows the company to carry out experimental prints of these scaffold models on a medium-range performing FDM 3D printer. The company uses a combination of different materials and printer configuration settings before finally arriving at the 3D PETG Cell Culture Scaffold product that is gaining global attention.
Inside the biotech
Copner Biotech
Copner Biotech’s 3D PETG Cell Culture Scaffold is the latest commercially available product to be added to its ever-evolving portfolio. The early success of that portfolio has helped the company to be in revenue for the last three years, attract 600,000 GBP in investor grant funding, and grow the team from three people to eight.
Prior to the introduction of the 3D PETG Cell Culture Scaffold product, the company had sought to address the shortcomings of conventional CAD to STL to g-code workflows with the development of its first 3D extrusion bioprinter. Backed by a SMART Cymru grant from Welsh Government, the machine boasts a 30 x 30 cm footprint, weight of around four kilogrammes and retail price of just 8,500 GBP. It has been designed as an entry-level platform that can facilitate the printing of scaffolds and basic tissue constructs, with control software enabling the reading and printing of GRAPE-derived models.
Development of the GRAPE S1 4D extrusion bioprinter swiftly followed, with this machine boasting improved printer movement resolution dictated by its CoreXY technique and a clean room type temperature-controlled enclosure. This closed chamber environment makes the system suitable for more complex materials requiring temperature stimuli, such as pure collagen. An Innovate UK grant from UK Government is now aiding the development of the company’s GRAPE S2 4D inkjet bioprinting, which is set to provide the company a launch pad into tissue engineering and organ replacement research activities. But more on that later.
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Both the GRAPE S1 3D and 4D Bioprinters harness microfluidic droplet deposition in combination with ‘raster-style, sequential print head movement.’ They are able to print hydrogels, with the machines capable of optimising the method of deposition to the user’s BioINK via the company’s ‘droplet optimisation protocol’, promising a ‘new level of precision and control.’
“We can print the gel, with high accuracy, and we’re not getting the inertia you typically see with syringe-based systems,” Jordan says of the extrusion process. “Because we’re using microfluidics in our delivery, we’re getting laminar flow and precise material control. We’re not getting the shear stress on the cells, so that cells can be put into the gel and printed and achieve high viability post-print.”
Copner Biotech
Copner Biotech has sought not only to provide quality, but also flexibility. It allows its users to process whatever inks and scaffolds they want, with operators able to optimise printer parameters to their preference. The only stipulation when deploying Copner’s bioprinting systems, is that to get the best out of them, you have to lean on the company’s GRAPE 3D modelling format.
It is, CTO Alan Copner explains, the company’s core innovation. GRAPE’s application of rectangles as the primitive construct units deliver what Copner Biotech believes is ‘superior modelling.’ The format has been developed to address the perceived challenge of modelling spherical structures in the STL format.
Copner Biotech is confident it has not only brought to market a modelling platform that is superior to STL, but also more user friendly, with a context sensitive graphical user interface (GUI) directing the user through the platform to make the design and manipulation of models easier and facilitate the creation of complex structures.
This software is not only supporting Copner Biotech’s 3D and 4D bioprinting products, but its application of traditional FDM 3D printing too.
Copner's core
It is, in fact, the foremost reason TCT is here today. On Jordan’s desk is a small plastic bag, completely transparent and without labels, there is only a QR code on the back and 12 PETG Cell Culture Scaffolds inside.
These PETG Cell Culture Scaffolds have been developed to address the constraints of cells grown in two-dimensional environments like petri dishes. These environments can generate forced polarity, whereas Copner’s 3D scaffolds are said to exhibit more physiologically relevant characteristics. As Jordan explains, when cells are placed in the 2D environment, they randomly distribute and form pockets, with areas of high cell growth and high cell death. It therefore is not replicating accurately the physiological tissue.
Copner Biotech, then, decided to work towards a solution. Its 3D scaffolds can be produced on concentric shape constructs (such as circles) to deliver a consistent variability of pore size and provide clear regions of scaffold where cells can benefit from more favourable nutrient and oxygen exchange. This, according to the company, enables constructs with better representations of physiological conditions in the body.
“What 3D culture looks to do is to take it one step closer to the real thing,” Jordan says. “The reason for that is to have cells that think they’re in the body so [you get] better drug responses and you help your cells. If you want to create tissues of interest, you need to have 3D, you can’t have a 2D model there.”
Where this solution fits in the cell culture research space are between 2D testing and animal testing, with Jordan noting how often companies will see their cells fail during expensive animal studies.
“If it works in the 3D environment, it will probably work in the animal, whereas if it doesn’t work in the 3D environment, you haven’t lost much money there. These retail at £130, so you could do a couple of tests in 3D, or you could do a £100,000 animal study. The choice is yours. That’s what they tell people, and they go the right way.”
Copner Biotech is additively manufacturing these PETG scaffold parts on standard FDM machines. But they are enabled by the company’s GRAPE modelling format.
“It creates these 3D files which are much more precise,” Jordan explains of the GRAPE modelling format. “It allows the printer to take on an atomic style of printing. It’ll finish a whole circle, then pause, move slightly, and do another whole circle. It’s not like normal 3D printing, which is constant, it is slowly taking its time, doing each circle and then once we build this up layer by layer, we’ve got those interconnected pores within the scaffold itself. In between the circle layers, there are strut layers. This is very atomic.”
Copner Biotech
Copner Biotech has combined the capabilities of its GRAPE modelling format and FDM 3D printing with a material selection that prioritised strength and stiffness. Having conducted research into PLA and polystyrene polycarbonate, it was concluded that PETG was the best bet. In addition to a ‘high Youngs modulus that is appreciated by cells,’ the PETG also promises a two-year shelf life and an ability to be stored and shipped at room temperature.
The company therefore believes it is offering a really good alternative to animal-based hydrogels. Copner Biotech sees animal-derived products as having a smaller shelf life, higher cost, and ‘huge batch to batch variability.’ Its 3D printed PETG scaffolds, on the other hand, it would describe as ‘off-the-shelf, animal-free, with high batch to batch consistency that can ship at room temperature.’
Typical applications of Copner Biotech’s PETG scaffolds include the development of organoids, cell culture, exosomes and therapeutic reagents. And as CFO Elizabeth Copner points out: “The organoids market alone was around 2.5 billion USD last year, with growth projections reaching up to 12.2 billion USD by 2030.” So, plenty for Copner Biotech to go after as it looks to rival animal-based hydrogels in addressing the needs of millions of biomedical scientists.
Going global
While solving problems for its customers is the name of the game, the animal-free PETG scaffolds will also provide Copner Biotech the opportunity to build its brand awareness across the globe. Though a potentially powerful product, the set-up is relatively simple for the company to scale, meaning Copner is confident it can reach all corners of the globe while additional R&D and go-to-market strategies commence in the background.
As Copner Biotech ramps up the distribution of its PETG scaffolds, it is also planning a Europe launch of its GRAPE S1 4D Bioprinter in 2025, and the launch of the GRAPE S2 4D inkjet-based bioprinting system in 2026. The inkjet system harnesses a patented technology – Negative Space Inkjet Printing – and processes low viscosity materials. It is set to be Copner Biotech’s step into the regenerative medical space by enabling the creation of vascularised tissue. The applications here would include developing tissues for organ replacement and personalised medicines for cancer patients, with Copner Biotech identifying a need to replace organs and complex tissues.
“The company is continually innovating,” explains CTO Alan Copner. “Research demands on biofabrication dictates that you have to keep pushing the boundaries and not settle for the conventional.”
Copner Biotech has secured funding from the Welsh Government to continue its work undertaken with Innovate UK to further develop the Negative Space Inkjet Printing technology. Once commercialised, the idea is to license out the technology to market leaders. That is the company’s end goal.
“Our goal is to be licensing to big pharma,” Jordan finishes. “The business is already creating that brand awareness and those contacts. Scaffolds is now, bioprinters are also now but in the UK, and then we should have a global distribution network, then moving on with the printers, and in the very future the regenerative medicine side of things, licensing that tech to the big guys. That’s the future of the business.”
