Commercial articulated collaborative in situ 3D bioprinter for skin wound healing

Aleksandr A. Levin^1†*, Pavel A. Karalkin^2,3†*, Elizaveta V. Koudan¹, Fedor S. Senatov¹, Vladislav A. Parfenov⁴, Vladislav A. Lvov¹, Stanislav V. Petrov¹, Frederico D. A. S. Pereira⁵, Alexey V. Kovalev⁶, Egor O. Osidak^7,8, Sergey P. Domogatsky⁷, Natalya E. Manturova⁹, Vladimir A. Kasyanov¹⁰, Natalia S. Sergeeva², Vadim L. Zorin^11,12, Yusef D. Khesuani⁵, Vladimir A. Mironov^1,6

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¹ Center for Biomedical Engineering, National University of Science and Technology “MISIS”, Moscow, Russia

² National Medical Research Radiological Center, P. A. Hertsen Moscow Oncology Research Center, Moscow, Russia

³ L. L. Levshin Institute of Cluster Oncology, Sechenov First Moscow State Medical University, Moscow, Russia

⁴ A. A. Baikov Institute of Metallurgy and Material Sciencen Academy of Sciences, Moscow, Russia

⁵ Laboratory for Biotechnological Research “3D Bioprinting Solutions”, Moscow, Russia

⁶ Priorov Central National Institute of Traumatology and Orthopedics, Moscow, Russia

⁷ Imtek Ltd., Moscow, Russia

⁸ Dmitry Rogachev National Medical Research Center of Paediatric Haematology, Oncology and Immunology, Moscow, Russia

⁹ JSC Plastic Surgery and Cosmetology Institute, Moscow, Russia

¹⁰ Joint Laboratory of Traumatology and Orthopedics, Riga Stradins University, Riga, Latvia

¹¹ Human Stem Cells Institute, Moscow, Russia

¹² SKINCELL LLC, Skolkovo, Moscow, Russia

†These authors contributed equally to this work.

IJB 2023, 9(2), 675 https://doi.org/10.18063/ijb.v9i2.675

Received: 1 December 2022 | Accepted: 13 December 2022 | Published online: 31 January 2023

© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

In situ bioprinting is one of the most clinically relevant techniques in the emerging bioprinting technology because it could be performed directly on the human body in the operating room and it does not require bioreactors for post-printing tissue maturation. However, commercial in situ bioprinters are still not available on the market. In this study, we demonstrated the benefit of the originally developed first commercial articulated collaborative in situ bioprinter for the treatment of full-thickness wounds in rat and porcine models. We used an articulated and collaborative robotic arm from company KUKA and developed original printhead and correspondence software enabling in situ bioprinting on curve and moving surfaces. The results of in vitro and in vivo experiments show that in situ bioprinting of bioink induces a strong hydrogel adhesion and enables printing on curved surfaces of wet tissues with a high level of fidelity. The in situ bioprinter was convenient to use in the operating room. Additional in vitro experiments (in vitro collagen contraction assay and in vitro 3D angiogenesis assay) and histological analyses demonstrated that in situ bioprinting improves the quality of wound healing in rat and porcine skin wounds. The absence of interference with the normal process of wound healing and even certain improvement in the dynamics of this process strongly suggests that in situ bioprinting could be used as a novel therapeutic modality in wound healing.

Keywords

In situ bioprinting

Wound healing

Bioink

Collagen hydrogel

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