A lot of technology breakthrough stories come from humble garages and garden shed, but it was a coffee shop in Derbyshire where the lift of the UK's lockdown restrictions this past Spring enabled 4D Biomaterials’ CEO Philip Smith and additive manufacturing (AM) consultant Phil Reeves to meet for the first time and experience one of their own.
“I told him what we were doing,” Smith recalled in a recent conversation with TCT. “[Phil] started laughing and said, ‘I've got a client, he's asked me to find that material. I've been looking all over the world for that material.’”
That material, or materials, is 4Degra, a range of novel polymeric 3D printing resin-inks (patents applied for) that can be used to additively manufacture implantable medical devices which degrade and resorb into the body over time.
It all started 15 years ago with Professor Andrew Dove, a leading researcher in degradable polymers, who started developing a new class of stereolithography-type resins that would deliver better patient outcomes. To commercialise the technology, 4D Biomaterials has since spun out of the Universities of Birmingham and Warwick, assembled a full-time team of six, secured a recent seed round of £1.6m, and is now ready to take the technology into its next phase.
Degradable polymers such as polylactic acid (PLA), poly lactic-co-glycolic acid (PLGA) and polycaprolactone (PCL) are well established in the medical device field, with some already able to be printed via processes such as FDM, but they can pose some limitations.
"With things like PLA and PLGA, which are polyesters, degradation is triggered by moisture and those materials in particular hydrate very easily," Dr Andy Naylor, Head of Product Development at 4D Biomaterials, explained. "So, when they go into the body, the water goes all the way through the material. That triggers a reaction causing them to degrade from the inside out. That degradation can lead to a potentially very acidic local environment, which is not very good for tissue and that's a key drawback with those materials."
By contrast, 4Degra materials degrade via a progressive surface erosion process that stops the structure itself from collapsing suddenly. This means that any by- products are also released much more gradually, resulting in reduced concentration levels. As tissue grows into the scaffold, this progressive erosion also improves the way the device itself is resorbed over time.
Lattice structured 3D printed in 4Degra
4D Biomaterials’ team of engineers and chemists is able to formulate the material for different needs. These can range from incredibly soft and flexible materials to those with rigid and strong properties. The company neighboured alongside TCT 3Sixty at the 2021 Med-Tech Innovation Expo where an array of application examples, from 3D printed lattice structures for bone regeneration to microstructures for splints, displayed the wealth of potential such material flexibility could bring. In one of the larger application examples, the materials were used to print a breast conserving lumpectomy device which is implanted into the void after the removal of a tumour. The device, printed in a soft tissue version of 4Degra, features a shape memory lattice structure and sponge-like quality, similar to breast tissue, so that it can be compressed into a smaller shape on implantation and then expand once it reaches body temperature. Over time, the patient’s natural tissue grows into the scaffold which will then degrade and be resorbed into the body. The device is said to have piqued the interest of breast surgeons in the U.S. who see this as a more efficient way of delivering better cosmetic outcomes without the need for reconstructive surgery.
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In a different example featuring a stiffer material formulation, a lattice structure was applied to bridge the gap in a fracture and promote bone growth. For more complex cases, thanks to 3D printing, these kinds of devices can also be personalised.
“Those types of tissue scaffolds, with a very well-defined pore size and very high resolution, are great for growing tissue through,” Naylor added. “You couldn't make it any other way other than 3D printing.”
Leveraging Reeves’ connections within the AM industry, the company has been working with early customers and machine vendors – both of which are being kept under wraps – to get the materials ready for clinical trials. While the team has plenty of ideas around where these materials could have an impact, Smith says the long-term intention is not to become a medical device manufacturer but rather a provider of materials and a development partner. Yet, getting a medical device through the necessary regulations is a long and rigorous process and currently, Reeves describes the “chicken and egg” situation the start-up finds itself in as it plans to select one device to focus on pushing through clinical trials to attain regulatory approval without relying on a third party to take the leap for them.
“It's just a way of us making sure we get the material in a device that's approved,” Smith adds, “and then that qualifies it as a material for other people to use in whichever device they're developing or have.”
Though, with what the team believes to be a “world-beating” material on their hands, Reeves argues that for those devices where 3D printing makes sense, 4Degra is a no brainer.
“The reality is, it doesn't matter what the material is, whether it's PEEK, whether it's titanium, whether it's known and accepted biomedical materials, you still have to go through this whole process for a medical device,” Reeves explained. “What excites me about this is that we have a better material than the incumbent material and it won't take necessarily any longer to get it into a medical device, if you want to use 3D printing.”
4Degra can be formulated for different application requirements
Whilst it was a serendipitous meeting of minds in a local café – and a short Happy Birthday exchange between Smith and Naylor over LinkedIn that evolved to finding a home and a kitted-out lab inside Nottingham’s MediCity – which led 4D Biomaterials to where it is today, the trio believe the switch to remote working and Zoomification of business meetings also played a part by creating a level playing field.
“We've had Zoom meetings with some of the biggest medical device manufacturers and 3D printing companies in the world,” Reeves shared. “We're a tiny start-up in Nottingham and I think pre-COVID there would have been an expectation that we would have to have travelled to them to be seen and I think that's completely changed now. I think it's become a much more level playing field in the way that you communicate with prospective partners and clients and supply chain partners.”
The start-up has ambitions to select its first device this year with intent to start human trials around 2023. Right now, the resin is only suitable for design development purposes but the next step is to engage with a GMP manufacturing facility to prepare the material for clinical trials. Once that is achieved, the possibilities could be boundless.
“I think we're actually in a pretty strong position that we've got, potentially, a world-beating material that’s better than what you've got, and it's 3D printable,” Phil concluded. “So, if you're a device manufacturer and you want to move into 3D printing, why would you do that using a substandard material?”
Visit 4D Biomaterials at TCT 3Sixty on 8-9 June, NEC Birmingham, HALL 9, A50.
