From Academia: In Vivo & Robotic-assisted Minimally InvasiveBioprinting, 3DP for Liver Surgery

Category: Blog,From Academia
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“From Academia” feature recent, relevant, close to commercialization academic publications in the space of healthcare 3D printing, bioprinting, and related emerging technologies. 

Email: Rance Tino ( if you want to pen an Expert Corner blog for us or want to share relevant academic publications with us.

Intravital three-dimensional bioprinting

– Authored by Anna Urciuolo, Ilaria Poli, Luca Brandolino, Paolo Raffa, Valentina Scattolini, Cecilia Laterza, Giovanni G. Giobbe, Elisa Zambaiti, Giulia Selmin, Michael Magnussen, Laura Brigo, Paolo De Coppi, Stefano Salmaso, Monica Giomo & Nicola Elvassore. Nature Biomedical Engineering, 22 June 2020

Intravital 3D bioprinting setup and in vivo application. a, i3D bioprinting requires a multiphoton microscope equipped with a motorized xyz stage and a femtosecond near-infrared tightly-focused pulsed laser emission. CAD, computer-aided design; CAM, computer-aided manufacture. b, i3D bioprinting is performed by injection of HCC–polymer solution into organs of live animals, fabrication of 3D hydrogel objects by two-photon excitation, and intravital imaging for hydrogel identification and in vivo analysis. Copyright.  Nature Biomedical Engineering


Fabrication of three-dimensional (3D) structures and functional tissues directly in live animals would enable minimally invasive surgical techniques for organ repair or reconstruction. Here, we show that 3D cell-laden photosensitive polymer hydrogels can be bioprinted across and within tissues of live mice, using bio-orthogonal two-photon cycloaddition and crosslinking of the polymers at wavelengths longer than 850 nm. Such intravital 3D bioprinting—which does not create by-products and takes advantage of commonly available multiphoton microscopes for the accurate positioning and orientation of the bioprinted structures into specific anatomical sites—enables the fabrication of complex structures inside tissues of live mice, including the dermis, skeletal muscle, and brain. We also show that intravital 3D bioprinting of donor-muscle-derived stem cells under the epimysium of hindlimb muscle in mice leads to the de novo formation of myofibres in the mice. Intravital 3D bioprinting could serve as an in vivo alternative to conventional bioprinting.

Direct-write 3D printing and characterization of a GelMA-based biomaterial for intracorporeal tissue

– Authored by A Asghari Adib, A Sheikhi, M Shahhosseini, A Simeunović, S Wu, C E Castro, R Zhao, A Khademhosseini and D J Hoelzle. Biofrabrication, 7 July 2020

Concept of intracorporeal tissue engineering. Operating room bed-mounted DW 3D printing system to 3D print patient-specific soft TE scaffolds in situ during surgery (a). Biomaterials/bioinks (inset) are 3D printed on the soft tissue inside the patient’s body (b). A novel interlocking mechanism to form stronger attachment of scaffold to the soft tissue (c). Intracorporeal TE via robotic-assisted minimally invasive 3D printing (d). Intracorporeal TE is a subset of in situ TE. A potential application of intracorporeal TE is minimally invasive intracorporeal 3D printing of a patient-specific TE scaffold to fill a liver wedge resection defect (e)–(f). Copyright. Biofabrication


We develop and characterize a biomaterial formulation and robotic methods tailored for intracorporeal tissue engineering (TE) via direct-write (DW) 3D printing. Intracorporeal TE is defined as the biofabrication of 3D TE scaffolds inside of a living patient, in a minimally invasive manner. A biomaterial for intracorporeal TE requires to be 3D printable and crosslinkable via mechanisms that are safe to native tissues and feasible at physiological temperature (37 °C). The cell-laden biomaterial (bioink) preparation and bioprinting methods must support cell viability. Additionally, the biomaterial and bioprinting method must enable the spatially accurate intracorporeal 3D delivery of the biomaterial, and the biomaterial must adhere to or integrate into the native tissue. Current biomaterial formulations do not meet all the presumed intracorporeal DW TE requirements. We demonstrate that a specific formulation of gelatin methacryloyl (GelMA)/Laponite®/methylcellulose (GLM) biomaterial system can be 3D printed at physiological temperature and crosslinked using visible light to construct 3D TE scaffolds with clinically relevant dimensions and consistent structures. Cell viability of 71%–77% and consistent mechanical properties over 21 d are reported. Rheological modifiers, Laponite® and methylcellulose, extend the degradation time of the scaffolds. The DW modality enables the piercing of the soft tissue and over-extrusion of the biomaterial into the tissue, creating a novel interlocking mechanism with soft, hydrated native tissue mimics and animal muscle with a 3.5–4 fold increase in the biomaterial/tissue adhesion strength compared to printing on top of the tissue. The developed GLM biomaterial and robotic interlocking mechanism pave the way towards intracorporeal TE.

Impact of 3D printing technology on the comprehension of surgical liver anatomy

– Authored by Tianyou Yang, Shuwen Lin, Qigen Xie, Wenwei Ouyang, Tianbao Tan, Jiahao Li, Zhiyuan Chen, Jiliang Yang, Huiying Wu, Jing Pan, Chao Hu, Yan Zou. Surgical Endoscopy. 18 June 2018. 

3D Printed model of patient MDCT (multi-detector computed tomography)(a) anterior view, (b) posterior view. CopyrightSurgical Endoscopy 


Surgical planning in liver resection depends on the precise understanding of the three-dimensional (3D) relation of tumors to the intrahepatic vascular trees. This study aimed to investigate the impact of 3D printing (3DP) technology on the understanding of surgical liver anatomy. We selected four hepatic tumors that were previously resected. For each tumor, a virtual 3D reconstruction (VIR) model was created from multi-detector computed tomography (MDCT) and was prototyped using a 3D printer. Forty-five surgical residents were evenly assigned to each group (3DP, VIR, and MDCT groups). After the evaluation of the MDCT scans, VIR model, or 3DP model of each tumor, surgical residents were asked to assign hepatic tumor locations and state surgical resection proposals. The time used to specify the tumor location was recorded. The correct responses and time spent were compared between the three groups. The assignment of tumor location improved steadily from MDCT, to VIR, and to 3DP, with a mean score of 34.50, 55.25, and 80.92, respectively. These scores were out of 100 points. The 3DP group had significantly higher scores compared with other groups (p < 0.001). Furthermore, 3DP significantly improved the accuracy of the surgical resection proposal (p < 0.001). The mean accuracy of the surgical resection proposal for 3DP, VIR, and MDCT was 57, 25, and 25%, respectively. The 3DP group took significantly less time, compared with other groups (p < 0.005). The mean time spent on assessing the tumor location for 3DP, VIR, and MDCT groups were 93, 223, and 286 s, respectively. 3D printing improves the understanding of surgical liver anatomy for surgical residents. The improved comprehension of liver anatomy may facilitate laparoscopy or open liver resection.

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