They say that practice makes perfect, and when it comes to major surgery, practice can be a matter of life and death. For Richard Arm – the man behind a new 3D printed liver – the desire to assist surgeons in these matters comes from a particularly personal place.
“I’ve had the idea for a while really, since my mother-in-law passed away with liver cancer,” Arm explained. “They were unable to operate on it. So I thought it would be good to try and provide some sort of opportunity for surgeons to practice and learn about the procedures before they go ahead, and help them plan for patient-specific procedures.”
Prior to the liver, Arm had worked on an MoD project known as the ‘thoracic trauma trainer’, a torso model with 3D printed heart and lungs to help train battlefield trauma surgeons. His background is in moulding, casting and prototyping, and he is currently a senior research fellow at Nottingham Trent University’s School of Art and Design, as well as a member of Trent’s Advanced Textiles Research Group (ATRG). Creating these lifelike synthetic organs requires a combination of artistic touch and feel as well as rigorous design and iteration, ensuring that the materials approximate the tactile feedback a surgeon would get when operating in real life.
“It’s definitely a collaboration, and an interdisciplinary one at that,” said Arm. “We speak to surgeons in the first instance and present them with a variety of materials.”
Experienced medics instinctively know what each organ feels like under various pressures, and consulting with them is an essential first step in the process. For the diseased liver most recently developed, Arm and his colleagues came up with numbers correlating to things like hardness and pliability for various parts, including blood vessels, liver tissue and tumours.
“We kind of reverse engineer it,” Arm explained. “We start with an experiential interpretation of the tissue, characterise that, then go back and ask it it’s correct.
“It’s about transferring that sort of tacit knowledge, the embodied knowledge of the surgeon into some sort of quantifiable numbers that we can use to base our further development on.”
As well as surgeons, key input also comes from radiologists who help decipher the data from the CT and MRI scans that the models are built on. For a large, complicated organ like the liver this is no mean feat, with blood vessels running across multiple axes, as well as a lymphatic system and bile ducts feeding the gall bladder.
“There’s lots of things happening in the liver,” said Arm. “The blood vessels are one of the main challenges. Interpreting how they overlap and interweave with one another. It’s like looking at a ball of roots on a tree. They’re all kind of meshed together and you have to pick one out by following the strand through.
“We use CT to map the blood vessels going through the organ then we overlay that with MRI just to verify that it is the correct blood vessel we’re looking at, and not just an anomaly in the scan.”
From the scan data, Arm and his team then make a multiplanar reconstruction of the organ, a digital version where different tissues and parts can be isolated in the model and printed separately, then assembled together into the complete liver. Post-print techniques developed in-house at Trent are then applied to transform the model from a rigid, printed structure to the tactile, pliable liver that surgeons can then work on.
“It’s very much a combination of fabrication know-how, what the materials do, and applying them in multiple layers to simulate not just the fidelity, but also the morphology of the organs,” Arm said. “By the third attempt we’d sort of nailed the process, and we want to roll that out now to the rest of the organs of the abdomen and start to explore that in a bit more detail.”
That final, third liver has only recently been completed and unveiled to the world, and although there has been extensive medical input throughout the development process, the finished product has yet to be put through its paces on the operating table. According to Arm, however, there has been no shortage of attention for the project, with surgeons both in the UK and abroad getting in contact to express interest in working with the synthetic organs.
“We’ve not had a chance to get a surgeon to operate on it yet,” said Arm. “We’ve made lots of contacts…there’s a liver surgeon in Leeds that’s interested. Obviously we’ve got liver specialists in QMC (Queen’s Medical Centre, Nottingham) that are interested. And further afield, in Canada, there’s a couple of surgeons that are interested. So there’s plenty of opportunity to test it, it’s just about creating enough prototypes so we can go ahead with proper user trials and validate what we’re doing.”
According to Arm, the 3D printed liver is a close enough analogue to the real thing that it can even be used to practice endoscopies and laser ablation techniques, where arteries are resealed by laser to prevent patients bleeding out during surgery. Another potential high-end use case is in the growing sector of robotic surgery. At seminars and conferences he attended pre-COVID, Arm witnessed cutting-edge and hugely expensive robotic platforms like DaVinci performing demonstrations on peppers.
“They’ve got this great big multi-million-pound machine and they’re practising on fruit and veg,” he said. “So it struck me that they were crying out for a tool to teach surgeons how to use this machine better.”
With advanced techniques like robotic surgery becoming more pervasive, it’s another potentially important market for realistic, synthetic organs. Ultimately, it’s about giving the medical profession as many tools as possible to improve skills and finesse techniques. Whether the scalpel is in the hand of a robot or a surgeon, understanding how organs respond is absolutely essential. Practising with 3D printed organs may not guarantee perfection, but it can almost certainly help improve patient outcomes across the board.
While this is an exceptional example, of course, additive manufacturing is now a relatively established technology in the manufacture of models (phantoms) for surgical planning and training, implants and prostheses, patient specific anti-microbial wound dressings, and some novel forms of drug delivery, but a relatively less advanced area is in the field of bioprinting and so called ‘organs-on-chip’.
The key stimulus behind AM driven bioprinting is to find a solution for organ / tissue rejection, and the requirement for lifelong immunosuppressant-based therapies. The area of regenerative medicine is constantly on the look-out for mechanisms that allow for the fabrication of multi-layer soft biological materials such as living cells, and in this extremely exacting area of research, AM is finding a foothold.
Wilgo Feliksdal, Co-Founder of FELIXprinters explains, “To date, AM has been mainly used for the preparation of tissue construct such as blood vessels, liver, kidneys, heart tissue, cartilage, and bone. But all developments in this area of the use of AM requires a focus on the long-term viability of the “printed” cells, the control of cell proliferation so as to provide sufficient amount of functional and supporting cells and tissue homeostasis, and the requirement for tissues used in 3D printing to be able to survive pressure and shear stress during the 3D printing process, as well as contact with potentially harmful compounds.”
With this in mind, FELIXprinters has launched its BIOprinter. This is characterised by key features that are specifically designed for medical, scientific, and research applications, including syringe cooling, print bed cooling and heating, a dual head system, easy syringe positioning (ergonomic access to the machine supports researchers in their work), and automatic bed levelling.
FELIXprinters has worked closely with the Technical University of Denmark (DTU) on bioprinting applications of 3D printing. Heading the research was Hakan Gürbüz, who explains the foundation of the work he is undertaking.
“The aim of the BIOprinter that we have developed with FELIXprinters is to allow the printing of scalable and perfusable hybrid scaffold structures, incorporating in the same structure at least two different material properties. For this purpose, we developed a hybrid 3D printing platform that enables the printing of 3D scaffolds with dual material properties (e.g. mechanical [soft/medium/hard], conductive or biological) and perfusable micro-channel networks, enabling the continuous supply of oxygen, nutrients, and necessary factors to cells growing and differentiating throughout the scaffold.”
3D printing has many advantages over conventional approaches to building scaffolds, not least its ability to position the cells precisely. Currently, there are three different classes of bioprinters that are used for deposition and patterning of biological materials including inkjet, micro-extrusion, and laser-assisted printing options. Each of these bioprinters has unique methods of depositing 3D cell structures with good resolution and viability. The FELIX BIOprinter is a micro-extrusion bioprinter, which makes it very simple to use.
Wilgo Feliksdal explains how micro-extrusion printers work. “Micro-extrusion bioprinters usually consist of a temperature-controlled biomaterial dispensing system, a stage capable of moving in the x, y, and z directions, light illuminated deposition area for photo-initiator activation, and a video camera for x-y-z command. Unlike other bioprinters, the micro-extrusion bioprinter generates a continuous string of bioink rather than many droplets of bioink by applying pressure – either pneumatically or mechanically – to force the bioink from a syringe.”
“These strings are deposited in two-dimensional layers (as directed by the CAD-CAM software), and served as the base for the subsequent layers while the stage is moved up the z-axis, resulting in the formation of a 3D structure. Micro-extrusion bioprinters are compatible with a wider selection of bioink including high viscosity materials such as hydrogels, biocompatible copolymers, and cell spheroids.”
Given its interdisciplinary nature, 3D bioprinting is accelerating at an ever-increasing rate. It’s exciting times, but we need to be careful to temper our expectations of this technology with the realities. The human body is incredibly complex and trying to replicate the many things that it does is difficult. Those working in the field are making advances every day, in both the technology and in their understanding of how it can be used and improved. There is no doubt that the future of medicine will be very different with bioprinting involved.
