Nested Biofabrication: Matryoshka‐Inspired Intra‐Embedded Bioprinting

Abstract 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.