Scientists 3D Printing In Situ for Tissue Regeneration

Robot-assisted in situ 3D bioprinting. Schematic illustration showing the concept of robot-assisted in vivo 3D bioprinting in the frame of minimally invasive surgery. (Reproduced with permission from Wanget et al.)

3D printing is all about cutting out the middleman and offering greater self-sustainability to some very happy users—enjoying the benefits of 3D printing from the factory, home, or office, whenever they like—and often however they like. Now, this benefit is being carried over to bioprinting in the lab as researchers are learning to cut out the middle step of growing cells in the lab (in vitro) and just implanting cells directly into the body for growth (in situ). This is 3D printing—and self-sustainability—at its most extreme, and in the abstract for ‘In situ three-dimensional printing for reparative and regenerative therapy’, the researchers state, and most likely quite correctly, that this study could garner significant attention.

The idea of in situ bioprinting will seem revolutionary to most of us, but as the authors state, it has been attempted before with some success, but challenges still required to overcome, from treating wounds to healing significant skin defects. One of the greatest benefits of being able to apply natural tissue at the natural site is that so many of the disadvantages of artificial implantation or transplants are eliminated with the ability to use biological elements from the patient themselves. This means avoiding infection as well as the potential for rejection by the body.

“Compared to other cell-based skin regenerative therapies, such as spraying keratinocytes or keratinocyte sheet, in situ printing shows the higher potential in addressing deeper wounds (i.e. deep into basal layer) by combining multi-material printing systems,” stated the researchers. “In addition, in situ printing can perform precise cell deposition for more efficient use of keratinocytes since it is difficult to culture for large-scale production.”

Bioprinted tissues must be grown with bioreactors in the in vitro environment, and the authors point out that customization and modifications may be necessary as size and shape may not be conducive to implantation at first. By printing tissues directly in vivo, many common challenges can be overcome.

The researchers point out that bioprinting offers tremendous potential for the area of tissue regeneration and repair. As with so many other types of bioprinting, numerous applications could lead to a better quality of life for patients—and in some cases even save their lives. This study could spread to other types of technology too such as those combining microfluidics–an area of study being heavily impacted by 3D printing and bioprinting currently, as we have seen in studies including liquid-in-liquid printing, scaffolds fabricated with sugar, and miniaturization.

This type of technology is so much less invasive overall that it offers great advantages to the patients, with less pain, less recovery time, less chance of infection, and less time spent in the hospital. The researchers foresee the chance of development and use of portable printers and mobile units too for emergency situations, as well as use in developing countries and areas that are remote. In situ bioprinting could also be used with robotics for a variety of surgical procedures.

Use of hand-held 3D bioprinting device for cartilage tissue regeneration. a A full-thickness cartilage defect was made in the medial and lateral femoral condyles of both stifle joints in sheep. b Images of intra-operative in situ 3D printing using a hand-held device. c Defect filled with HA-GelMA and MSCs and coated with fibrin glue spray. The defect was fully filled exhibiting curvature of the femoral condyle. d Macroscopic image of the retrieved treated cartilage defect. (Reproduced with permission from Di Bella et al.)

“This novel research field provides great potential for tissue engineering and regenerative medicine applications where preoperative planning of construct size and shape is difficult or impossible to predict,” concluded the researchers. “Advances in robotic surgery, fused imaging, and computer-assisted medical interventions should also be integrated to develop future clinical in situ 3D bioprinting processes, which can be translated to products for a variety of surgical applications.”

in situ laser-assisted 3D bioprinting. Proof of concept for in situ printing using laser-assisted bioprinting for depositing of HAp into a critical-size mouse calvarial defect. Different geometric cell patterns were 3D bioprinted for guiding the regeneration of bone tissue. (Reproduced with permission from Keriquel et al.)