Intraoperative Bioprinting

Restoring the structure and function of injured tissues can be challenging to perform when using conventional implants. 3D bioprinting has evolved to the point of allowing the fabrication of constructs that can be pre-engineered to precisely fit defect size and shape. The majority of bioprinting attempts to promote organ regeneration have been conducted in vitro and, in some cases, further validated with in vivo models [1,2].


Following the advance of 3D organ bioprinting, some attempts have been made in the field of intraoperative bioprinting (IOB), also known as in situ bioprinting. This technology seeks to directly perform solid organs’ bioprinting in a living human body in a surgical environment. Even though it still remains ideological, the IOB directly at injury sites is very promising. It can smooth out obstacles related to tissue’s complex heterogeneity in an anatomically accurate manner, eliminating the risk of rejection. This field is continuously advancing, even without any clinical performance to date, thanks to the joint efforts of researchers from different domains [1,2].


Figure 1: A conceptual vision of an IOB system compatible with minimally invasive surgeries [3].


As the largest and most easily accessible organ in the body, the skin is the most suitable place to start developing IOB [3,4]. In 2019, Albanna et al. developed a mobile skin bioprinting system in which all components are integrated to be mobilized in the operating room. This integrated technology facilitated the precise delivery of dermal fibroblasts and epidermal keratinocytes directly to an injured area, replicating the skin’s layered structure. The wounds showed a rapid closure, in addition to an accelerated reepithelization [4].


Intraoperative bioprinting has also been tested for the treatment of a chondral defect in a sheep model, through the development of portable devices. The mobile 3D printing device in question allows simultaneous coaxial extrusion of bioscaffold cells to be cultured directly in the cartilage defect in vivo during a single surgery session. According to the results, this approach was a viable method to promote articular cartilage regeneration in a large animal model [5].

Figure 2: IOB is used to treat a full-thickness chondral defect in a sheep [5].


IOB technology still requires several improvements in order to make fully functional complex tissues possible. In contrast, this field has been developing very fast in recent years, presenting several studies with immense potential, especially in skin, bone, and cartilage repair. With increasing investments in this area, it is safe to say that intraoperative bioprinting will become a reality in the near future [6].





REFERENCES


1. Wu, Y., Ravnic, D. J. & Ozbolat, I. T. Intraoperative Bioprinting: Repairing Tissues and Organs in a Surgical Setting. Trends Biotechnol. 38, 594–605 (2020).

2. Ashammakhi, N. et al. In situ three-dimensional printing for reparative and regenerative therapy. Biomed. Microdevices 21, 42 (2019).

3. Wang, M. et al. The trend towards in vivo bioprinting. International Journal of Bioprinting 1, (2015).

4. Albanna, M. et al. In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds. Sci. Rep. 9, 1856 (2019).

5. Singh, S., Choudhury, D., Yu, F., Mironov, V. & Naing, M. W. In situ bioprinting – Bioprinting from benchside to bedside? Acta Biomaterialia vol. 101 14–25 (2020).

6. Bella, C. D. et al. In situ handheld three‐dimensional bioprinting for cartilage regeneration. Journal of Tissue Engineering and Regenerative Medicine vol. 12 611–621 (2018).


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