Introduction
Three-dimensional (3D) bioprinting offers immense potential in biomedical applications, particularly for in vivo fabrication of bio-tissues and devices on internal organs. Current in vivo bioprinting techniques are largely restricted to superficial applications near the skin, such as skin or cartilage repair, or require invasive surgery for internal organ printing. This limitation stems from challenges like the low penetrability of light sources in light-induced polymerization (limiting depth to around 5 mm) and the inability of rigid nozzle printers to navigate the complex anatomy of the body. Minimally invasive in vivo bioprinting, therefore, presents a significant advancement, requiring novel solutions. Recent progress in soft robotics, particularly magnetoactive robots, offers a promising avenue. These robots, remotely controlled to navigate challenging environments, have shown potential in endovascular interventions and drug delivery. This research introduces a ferromagnetic soft catheter robot (FSCR) system integrating magnetic actuation with 3D printing to address the limitations of existing methods. The goal is to develop a system capable of minimally invasive in vivo bioprinting of functional inks, such as lesion healing creams and electrode gels, by using a slender, remotely controlled device that can reach internal body regions through small incisions.
Literature Review
The paper reviews existing 3D bioprinting methods, highlighting their limitations in minimally invasive applications. It discusses the challenges associated with current in vivo bioprinting techniques, particularly the limitations of light-induced polymerization due to limited light penetration and the difficulties of using conventional rigid nozzle printers in the confined and tortuous environments within the body. The authors then examine advancements in soft robotics, especially the use of magnetoactive robots for minimally invasive procedures. They mention the advantages of magnetic robots for remote control and navigation in hard-to-reach areas, referencing previous work on ferromagnetic soft guidewire robots. This review sets the stage for the introduction of the FSCR system, emphasizing the need for a novel approach that combines the benefits of both soft robotics and 3D bioprinting for minimally invasive applications.
Methodology
The study details the design and fabrication of a ferromagnetic soft catheter robot (FSCR). The FSCR is a slender, rod-like structure with a hollow channel for material transport. It is fabricated using an injection molding method, incorporating a ferromagnetic composite ink (polydimethylsiloxane (PDMS) with dispersed neodymium iron boron (NdFeB) particles) and a polylactide (PLA) fiber mesh for reinforcement. The fiber mesh enhances mechanical performance and prevents lateral expansion of the printing channel during ink extrusion, ensuring stable and controlled material deposition. The FSCR is magnetized to saturation along its axial direction, allowing for remote magnetic manipulation. The authors meticulously describe the material properties and characterization methods, including cytotoxicity testing to ensure biocompatibility. A magnetically controlled printing system is also developed, utilizing four numerically controlled motor-driven permanent magnets to precisely control the FSCR's translational and rotational motion. The magnetic field distribution generated by these magnets was experimentally measured and used to validate a finite element model of the FSCR's behavior under magnetic actuation. The printing process involves converting the desired pattern into catheter-path codes based on the established relationship between magnet displacements and FSCR tip displacements. The authors demonstrate the system's ability to print various patterns with different functional inks (silicones, silver pastes, conductive hydrogels) on both flat and curved surfaces. *In vitro* and *in vivo* experiments are conducted, utilizing porcine tissue and a rat liver model, respectively, to validate the system's efficacy in minimally invasive bioprinting. The detailed protocols for ink preparation, mechanical testing, and the *in vivo* procedures are provided.
Key Findings
The research successfully demonstrates the feasibility of minimally invasive in vivo bioprinting using the FSCR system. Key findings include: 1) The development of a biocompatible and mechanically robust FSCR with stable ink extrusion capabilities. The PLA reinforcement significantly reduces lateral expansion during high-pressure ink extrusion, improving printing resolution and speed, while minimally affecting the FSCR’s bending behavior under magnetic fields. 2) A precisely controlled magnetic actuation system allows for accurate and automated 3D printing on both flat and curved surfaces. The system uses four permanent magnets for intuitive control and precise motion, with the tip motion closely correlated to magnet movements. 3) Successful printing of various patterns using different functional inks (viscoelastic materials, conductive silver ink, and conductive hydrogels) on flat substrates and more complex, three-dimensional forms. The system achieves high fidelity reproduction of designed patterns. 4) Successful *in vitro* minimally invasive bioprinting on a porcine tissue phantom, showing precise pattern deposition on a curved and wet surface. This demonstrated the versatility of the system to adjust printing parameters to match non-planar surfaces. 5) Successful *in vivo* minimally invasive bioprinting of a conductive hydrogel onto the surface of a rat liver through a small incision, achieving a functional printed structure. The authors highlight the capability of using CT imaging to aid in reconstruction of the liver's 3D shape, which enables precise path planning for printing on the irregular surface. The entire *in vivo* process was accomplished in a minimally invasive manner and was completed within 70 s. 6) The FSCR was shown to manipulate objects of different weights (0.5–5g) both in liquid and solid forms, demonstrating its adaptability for multiple tasks during surgery.
Discussion
The findings demonstrate the potential of the FSCR system to revolutionize in vivo bioprinting. The ability to print functional materials on curved surfaces, including within a living organism, opens up new possibilities for tissue engineering, regenerative medicine, and implantable device fabrication. The minimally invasive nature of the system reduces the risk of infection and accelerates patient recovery compared to traditional open surgery methods. The precise control offered by the magnetic actuation enables the creation of complex three-dimensional structures, exceeding the limitations of previous approaches. The successful *in vivo* bioprinting in the rat liver model validates the system's clinical potential. However, further optimization is needed to improve the system's speed and resolution, particularly for more intricate designs and in complex anatomical environments.
Conclusion
This paper presents a significant advance in minimally invasive in vivo bioprinting through the development of a ferromagnetic soft catheter robot system. The system’s ability to print functional materials with high precision on both flat and curved surfaces, including within a living organism, is a major accomplishment. Future work should focus on further miniaturization, increased printing speed and resolution, and integration with real-time imaging and feedback mechanisms. Exploring the use of a wider range of biocompatible inks and extending the technology to other organs and applications are important next steps.
Limitations
While the FSCR demonstrates significant potential, several limitations should be considered. The current printing speed and resolution may need improvement for more complex three-dimensional structures. The system relies on CT imaging for pre-operative planning, limiting its adaptability to unforeseen anatomical variations during surgery. Integrating real-time imaging and feedback mechanisms to address this would be beneficial. The range of printable materials is currently limited, and expanding the biocompatibility and functional properties of available inks is necessary for broader applications. The long-term biocompatibility and efficacy of the printed materials *in vivo* need further investigation.
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