Robotic-based in situ bioprinting

Bioprinting has provided several advantages to traditional tissue engineering approaches for fabricating scaffolds for organ/tissue regeneration thanks to a precise and controlled biomaterials processing. Nevertheless, this technology, also known as in vitro bioprinting, suffers from several limitations when considering its clinical application, such as scaffold handling difficulty, risk of contamination, need of a maturation period in a bioreactor and shape/morphology of the bioprinted construct not perfectly matching with the defect site.

For these reasons, in situ bioprinting has emerged as a promising alternative technology. It consists in the direct deposition of biological material into the patient, following the complex geometry of the anatomical defect. This approach guarantees an enhancement in the maturation and differentiation of the bioprinted constructs, since the patient body itself works as a bioreactor. Currently, two different approaches have been proposed: the hand-held approach, where a portable device with a bioprinting unit is used for the direct biomaterial deposition; and the robotic approach, based on the use of a robotic manipulator with 3 or more Degrees of Freedom (DoF). The latter involves less human intervention and guarantees higher precision thus allowing the regeneration of complex defects [1].

A robotic bioprinting platform, named IMAGOBot, was developed to analyse the potential and limitations of such approach in the in situ bioprinting field. IMAGOBot is based on the open source MOVEO robotic arm from BCN3D [2]. The original project was modified as follows: i) the gripper was replaced by an electromagnet for quick tool-change; ii) each joint was equipped with incremental encoders; iii) the hardware was re-engineered to control the robot using Linux-CNC [3].

The operating pipeline can be divided into three main phases: i) surface reconstruction and defect localization, ii) path planning and iii) bioprinting. During the reconstruction/localization phase, IMAGOBot performs a scanning of the substrate with a touch probe equipped with a light sensor, acquiring a point cloud by touching the surface. For each point, the system records the coordinates of the surface point (obtained from the light sensor) and the depth of penetration (acquired from the spring-based probe). Knowing mechanical properties of the probe, the substrate stiffness can be evaluated. The reconstructed mesh of the substrate is then used for the path planning. In brief, the algorithm automatically projects any generic printing pattern on the mesh on which the scaffold will be printed. For each point, the normal direction is calculated to successively constrain the end-effector orientation, keeping it always perpendicular to the surface.

All tests carried out showed promising results and highlighted the potential that a robotic platform can have for in situ bioprinting. The robot was able to recognize the stiffness of the substrates with a reconstruction accuracy of 200 µm and print onto irregular surfaces following the imposed trajectory and dispensing a biocompatible hydrogel precisely and continuously. This approach opens the way to several possibilities in the field of tissue engineering, especially for the easiest accessible organs such as skin, bone and cartilage.

[1] Satnam, S. et al. – Acta biomaterialia, 2019

[2] Fortunato, G.M. et al. – Bioprinting, 2021

[3] Staroveški, T. et al. – Tehnički vjesnik, 2013

A presentation by Giovanni Vozzi, Full Professor – PhD in Bioengineering, University of Pisa.

Interview

Question 1: What drives you?
The willingness to share one of the most promising technologies in the field of biofabrication, which may in future make the process of patient-specific organ and tissue regeneration safer and faster.

Question 2: Why should the delegate attend your presentation?
The in situ bioprinting technology is fully integrated in the field of 3D printing in the medical field, but as it is a young technology, there are still few applications. In my presentation I will show an innovative in situ bioprinting platform that may be of interest to other delegates in order to learn more about the potential and limitations of this technology.

Question 3: What emerging technologies / trends do you see as having the greatest potential in the short and long run?
The in situ bioprinting technology definitely has potential, although it is not yet ready to go to market in the short term. A more extensive testing phase is still required in order to be able to print directly on humans. On the other hand, other bioprinting technologies for the manufacturing of implantable artificial substitutes will be able to find a faster clinical application, although with the limitations described in my presentation, which in situ bioprinting aims to overcome.

Question 4: What kind of impact do you expect them to have?
The impact of in situ bioprinting will be important in the field of regenerative medicine. Taking benefit of technological advances in robotic surgery, which has made some surgical procedures minimally invasive, in situ bioprinting will make it possible to work directly on the patient with extreme precision and repeatability, avoiding human error and automating and speeding up the process of regenerating organs and tissues.

Question 5: What are the barriers that might stand in the way?
Barriers at the moment concern not only the improvement of technology, but also the development and study of appropriate materials for direct deposition in a physiological environment. The materials must not only be compatible with the deposition process (in terms of rheological properties, for example), but also with those of the target tissue to be repaired (mechanical and biochemical properties) as well as with the hostile physiological environment (for instance, capable of self-sustaining in an aqueous environment). In addition, during the pre-clinical testing phase, a significant amount of in vivo testing on animals will certainly be required, which may represent an ethical issue.

About Giovanni Vozzi
Giovanni Vozzi was graduated in Electronic Engineering in 1998 at the University of Pisa. In 2002 he got the PhD in Bioengineering at Polytechnical of Milan. At present he is a full professor in Bioengineering.. He was member of Board of Directors of International Society of Biofabrication and now he is treasurer of this Society, of which he was founder, he is member of board of Directors Of National Group of Bioengineering and he is member of of IEEE.
His principal research interests are focused on biomaterials, tissue engineering, regenerative medicine and Biofabrication and in silico cell modeling.

About University of Pisa
The University of Pisa (UNIPI) is a public institution with twenty departments, and high level research centres in the agriculture, astrophysics, computer science, engineering, medicine and veterinary medicine sectors. Furthermore the University has close relations with the Pisan Institutes of the National Board of Research, with many cultural institutions of national and international importance, and with industries, especially those based in information technology, which went through a phase of rapid expansion in Pisa during the nineteen sixties and seventies.
UNIPI was officially established in 1343, although a number of scholars claim its origin dates back to the 11th century.

Giovanni Vozzi is speaker at the 2022 edition of the 3D BioPrinting Conference.

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