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REVIEW ARTICLE

3D-printed/bioprinted systems for spatially and temporally controlled drug delivery within tumor microenvironment

Yuan Wu1* ,  Yaying Xu1 ,  Jukai Zhang1 ,  Yile Wang1 ,  Zhouyi Sun2* ,  Zihao Guo1*
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1 College of Jiyang, Zhejiang A&F University, Zhuji, China
2 Department of General Surgery, Center for Oncology Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
IJB, 026170149 https://doi.org/10.36922/IJB026170149
Received: 22 April 2026 | Revised: 25 May 2026 | Accepted: 5 June 2026 | Published online: 6 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The pronounced spatial heterogeneity and dynamic evolution of the tumor microenvironment represent key factors limiting the sustained therapeutic efficacy of anti-tumor drugs in solid tumors. Traditional drug delivery strategies often rely on spatiotemporally uniform delivery profiles, making it difficult to match the complex structural organization and continuously evolving biological states within tumor tissues. This results in uneven drug distribution, limited therapeutic windows, and the development of drug resistance. In recent years, 3D-printing and bioprinting technologies, as layer-by-layer manufacturing methods based on digital design, have provided new solutions for constructing drug delivery systems with modifiable structures, partitioned spatial organization, and programmable time-release capabilities. By precisely controlling the arrangement of materials, bioactive molecules, and cells in three-dimensional space, these systems can not only achieve fine spatiotemporal regulation of the drug delivery process but also integrate cells, extracellular matrix, and mechanical cues during delivery, thereby partially reshaping the tumor microenvironment. This paper systematically reviews the design strategies and latest advancements of 3D-printing and bioprinting delivery systems in achieving spatiotemporally controllable drug delivery within the tumor microenvironment, focusing on their advantages in spatial regulation, temporal response, and tumor microenvironment reprogramming, while analyzing the current key challenges and clinical translation prospects, aiming to provide references for the rational design of next-generation tumor delivery systems.

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Keywords
3D-printed
Bioprinted
Drug delivery
Tumor microenvironment
Clinical translation
Funding
This work was supported by research development fund for talent startup project of Jiyang College, Zhejiang A&F University (RC2025F02), General Scientific Research Project of Zhejiang Provincial Department of Education in 2025 (Y202558493), and the special research fund of the China Pearl College (JYZZ202506).
Conflict of interest
The authors declare that they have no conflict of interest related to this work.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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