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[Preprint]. 2023 Oct 1:2023.09.28.560028. [Version 1] doi: 10.1101/2023.09.28.560028

Nested biofabrication: Matryoshka-inspired Intra-embedded Bioprinting

Mecit Altan Alioglu, Yasar Ozer Yilmaz, Yogendra Pratap Singh, Momoka Nagamine, Nazmiye Celik, Myoung Hwan Kim, Vaibhav Pal, Deepak Gupta, Ibrahim T Ozbolat
PMCID: PMC10557751  PMID: 37808743

Abstract

Engineering functional tissues and organs remains a fundamental pursuit in biofabrication. However, the accurate constitution of complex shapes and internal anatomical features of specific organs, including their intricate blood vessels and nerves, remains a significant challenge. Inspired by the Matryoshka doll, we here introduce a new method called 'Intra-Embedded Bioprinting (IEB),' building upon existing embedded bioprinting methods. We used a xanthan gum-based material, which served a dual role as both a bioprintable ink and a support bath, due to its unique shear-thinning and self-healing properties. We demonstrated IEB's capabilities in organ modelling, creating a miniaturized replica of a pancreas using a photocrosslinkable silicone composite. Further, a head phantom and a Matryoshka doll were 3D printed, exemplifying IEB's capability to manufacture intricate, nested structures. Towards the use case of IEB and employing innovative coupling strategy between extrusion-based and aspiration-assisted bioprinting, we developed a breast tumor model that included a central channel mimicking a blood vessel, with tumor spheroids bioprinted in proximity. Validation using a clinically-available chemotherapeutic drug illustrated its efficacy in reducing the tumor volume via perfusion over time. This method opens a new way of bioprinting enabling the creation of complex-shaped organs with internal anatomical features.

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