Journal Article

Programmable embedded bioprinting for one-step manufacturing of arterial models with customized contractile and metabolic functions

Yang, Huayong, Gao, Ziqi, Li, Qi, Zhao, Hui, Du, Huilong, Yu, Shuyuan, Zhou, Hongzhao, Wang, Yuxuan, Shen, Luqi

2025

Overview

The macro 3D circumferential orientation and high cellular alignment of vascular smooth muscle cells (VSMCs) are crucial for vascular activity. Our voxel-based embedded construction for tailored orientational replication (VECTOR) method can replicate arterial structures with both macro and cellular-scale alignment.A new metric, voxel vector magnitude (VVM), is proposed to represent the resultant cellular force in the printed structure, of close relevance to the contractile function. Transcriptomics analysis shows that VSMCs in high VVM structures switch to contractile phenotypes.The dual-scale alignment of cells enhances the contractility and metabolic functions of the fabricated structures.Omnidirectionally bioprinted triple-layered artery models with tunica intima, media, and adventitia promote biomimetic cellular crosstalk and drug response, demonstrating the importance of structural similarity. Replicating the contractile function of arterial tissues in vitro requires precise control of cell alignment within 3D structures, a challenge that existing bioprinting techniques struggle to meet. In this study, we introduce the voxel-based embedded construction for tailored orientational replication (VECTOR) method, a voxel-based approach that controls cellular orientation and collective behavior within bioprinted filaments. By fine-tuning voxel vector magnitude and using an omnidirectional printing trajectory, we achieve structural mimicry at both the macroscale and the cellular alignment level. This dual-scale approach enhances vascular smooth muscle cell (VSMC) function by regulating contractile and synthetic pathways. The VECTOR method facilitates the construction of 3D arterial structures that closely replicate natural coronary architectures, significantly improving contractility and metabolic function. Moreover, the resulting multilayered arterial models (AMs) exhibit precise responses to pharmacological stimuli, similar to native arteries. This work highlights the critical role of structural mimicry in tissue functionality and advances the replication of complex tissues in vitro. [Display omitted] This work introduces a new method, voxel-based embedded construction for tailored orientational replication (‘VECTOR’), that can achieve macro-level circumferential orientation and micro-level cellular alignment. It can be used to fabricate in vitro arterial models with enhanced contractile and metabolic functions. Our study highlights the crucial role of anatomical structural similarity in replicating tissue function. Our voxel-based embedded construction for tailored orientational replication (VECTOR) technology is currently at Technology Readiness Level (TRL) 3, with experimental proof of concept achieved in controlled laboratory settings. The primary challenges for advancing to higher TRLs include optimizing voxel control for larger and more complex 3D structures, and ensuring reproducibility and scalability across different tissue types. To overcome these challenges, further research and development are necessary, including refining bioprinting techniques, conducting extensive in vitro testing, and developing protocols for integration with existing biomanufacturing processes. Policy implications involve the need for standardized bioprinting guidelines and regulatory frameworks to ensure consistent and safe application of this technology in research and clinical settings.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: 3D bioprinting / Alignment / Animals / arterial model / Arteries / Arteries - cytology / Arteries - physiology / Bioprinting - methods / Cells / cellular alignment / Cellular structure / embedded bioprinting / Filaments / Humans / Internal Medicine / Metabolism / Mimicry / Muscle contraction / Muscle, Smooth, Vascular - cytology / Myocytes, Smooth Muscle - cytology / Physiology / Printing, Three-Dimensional / Process controls / Replication / Smooth muscle / Three dimensional printing / Tissue Engineering - methods / Tissue Scaffolds / Veins & arteries / voxel