14-09-2021 | By Liam Critchey
3D printing technologies have gained much traction in different sectors, including in one of the most highly regulated industries—the medical industry. 3D printing has already gained a lot of interest for creating surgical tools and implants, and the interest in the medical sector has also extended to in-vivo bioprinting. In-vivo bioprinting is the direct printing of organic and biological matter inside the human body to create artificial tissues and print small medical devices on target sites.
In-vivo bioprinting is potentially seen as the future for healing organs by directly healing the tissue at the site and the facilitator of the next generation of medical monitoring. Printing the devices directly onto organs (in a minimally invasive manner) could help to reduce the need for implant surgeries—so long as there’s a seamless integration between the printed material and the biological matter inside the body.
Given the regulation in the medical sector and the fact that 3D bioprinting is not as widely tested or regulated yet, the area is still in its infancy compared to other 3D printing technologies. However, there is much interest in using 3D printing methods in the medical sector, so these technologies may be incorporated into regulations soon. We could start to see 3D printing, including in-vivo bioprinting, becoming a more common sight in the medical sector.
Even though in-vivo bioprinting holds a lot of promise for tissue engineering and human-interface applications, the sector is still in its infancy. Currently, many of the trials and applications involving in-vivo bioprinting take place at or near the skin level. Some of the applications trialled to date include skin or cartilage repair by direct ink writing or the fabrication of epidermal electrodes.
In its current state, surgical operations are typically required for in-vivo bioprinting to occur inside the body, such as on the internal organs. While the processes are more invasive, there has been some success, including printing patterned biopolymers under the skin and the direct writing of ink inside gastric chambers.
The invasive nature of many of these approaches means a higher risk of infection and a much longer recovery time for patients than if the process was minimally invasive. While many of the techniques to date are more invasive, soft robotics is starting to offer a way of making these surgical processes less invasive by providing an alternative solution to the conventional rigid printer nozzles. These types of nozzles have been responsible for the limited application scope inside the body (as the rigid nozzle struggle to penetrate and navigate the internal biological landscape of the body).
Where traditional and more rigid printing nozzles are failing, softer robotic printing nozzles offer a potential solution to make in-vivo bioprinting a minimally invasive surgical approach. Advances in soft robotics have created robotic systems capable of dextrous manipulation, making them much more suitable for navigating the dynamically changing, confined and deformable environment of the human body. In addition to these properties, several magnetoactive robots have been designed to be controlled remotely to navigate hard-to-reach areas of the body.
The remote and untethered control of magnetoactive robots is gathering much interest for many in-vivo bioprinting applications. Such applications include endovascular interventions and drug delivery to targeted lesions.
The most promising soft robotics are ferromagnetic systems, where a guidewire is created using ferromagnetic particles that are dispersed in a polymer matrix. The inclusion of the ferromagnetic particles means that the robotic wire can actively bend upon magnetic actuation, and its tip can be steered through the ever-changing biological landscape. While these types of robotic guidewires have shown promise on their own thanks to their steering and navigation capabilities, they can also be integrated with other advanced technologies for more complex biomedical applications.
Researchers from China have now created a ferromagnetic soft catheter robot (FSCR) compatible with 3D bioprinting techniques. The FSCR is a slender rod-like structure that possesses magnetic actuation (thanks to embedded magnetic particles). It can be controlled when navigating biological environments (using motor-driven permanent magnets). It has been designed for minimally invasive in-vivo bioprinting approaches. The approach enabled the FSCR to navigate the body, followed by in-situ printing of different functional inks such as lesion healing creams or electrode gels.
The FCSR was designed by dispersing hard ferromagnetic (NdFeB) particles into a polymer matrix (PDMS), and this was wrapped in a reinforcing fibre mesh (made up of PLA fibres) to make the extrusion of inks steadier during printing. The FCSR was connected to a magnetoactive soft printing nozzle that could print over a large area but only required a small incision to be made for it to be inserted during the surgical process.
The FCSR system can print various materials with different rheological properties and functionalities, including silicones, silver pastes, and conductive hydrogels, in a controlled and accurate manner. The FCSR system also showed printing capabilities on a range of surfaces. This was showcased first by printing different patterns (with the different functional inks) on planar surfaces, followed by non-planar surfaces—such as those which mimic the natural shape of organs.
After showcasing the capabilities of the printing technology, the researchers developed an in-situ printing strategy for curved surfaces. They demonstrated minimally invasive in-vivo bioprinting of hydrogels in a rat model. In this demonstration, the team printed a functional hydrogel on a porcine tissue phantom and a living rat’s liver in a process controlled in a remote and automated manner.
Despite the infancy of the field and trials being on a rat and not a human, there are promising signs with soft robotic catheters for in-vivo bioprinting scenarios. We might start seeing more and more as new ways of bioprinting inside biological tissue/biological environments become available—especially as there is growing interest in all forms of 3D printing in the medical sector.
Zang J. et al, Ferromagnetic soft catheter robots for minimally invasive bioprinting, Nature Communications, 12, (2021), 5072