Nested Biofabrication: Matryoshka-Inspired Intra-Embedded Bioprinting

Alioglu M. A., Yilmaz Y. O., Singh Y. P., Nagamine M., Celik N., Kim M. H., ...More

Small Methods, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2023
  • Doi Number: 10.1002/smtd.202301325
  • Journal Name: Small Methods
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, Compendex, INSPEC, MEDLINE
  • Keywords: bioprinting, cancer-on-a-chip, intra-embedded bioprinting, organ modeling
  • Istanbul Technical University Affiliated: No


Engineering functional tissues and organs remains a fundamental pursuit in bio-fabrication. 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, here a new method called “Intra-Embedded Bioprinting (IEB)” is introduced building upon existing embedded bioprinting methods. a xanthan gum-based material is used which served a dual role as both a bioprintable ink and a support bath, due to its unique shear-thinning and self-healing properties. IEB's capabilities in organ modeling, creating a miniaturized replica of a pancreas using a photocrosslinkable silicone composite is demonstrated. Further, a head phantom and a Matryoshka doll are 3D printed, exemplifying IEB's capability to manufacture intricate, nested structures. Toward the use case of IEB and employing an innovative coupling strategy between extrusion-based and aspiration-assisted bioprinting, a breast tumor model that included a central channel mimicking a blood vessel, with tumor spheroids bioprinted in proximity is developed. 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.