AccScience Publishing / IJB / Volume 12 / Issue 1 / DOI: 10.36922/IJB025440447
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REVIEW ARTICLE

Extracellular matrix-inspired 4D SMART biomaterials for bioprinting in tissue engineering

Ryan Martin1 ,  Haiwei Zhai2 ,  Daehoon Han3 ,  Fanben Meng2,4* ,  Daeha Joung1,5*
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1 Department of Physics, College of Humanities and Sciences, Virginia Commonwealth University, Richmond, Virginia, United States
2 Department of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, United States
3 School of Chemical Engineering, Chonnam National University, Gwangju, Republic of Korea
4 Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, Nebraska, United States
5 Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, Virginia, United States
IJB 2026, 12(1), 225–261; https://doi.org/10.36922/IJB025440447
Received: 29 October 2025 | Accepted: 26 December 2025 | Published online: 12 January 2026
(This article belongs to the Special Issue Multidisciplinary Efforts in Bioprinting)
© 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

Tissue development and regeneration arise from a dynamic interplay among cells, the extracellular matrix (ECM), and surrounding biophysical and biochemical cues. These interactions form the basis for stimuli-responsive materials for advanced regenerative technologies (SMART) that drive innovation in four-dimensional (4D) bioprinting for tissue engineering. This review discusses the biophysical foundations of SMART materials, emphasizing native ECM components, their interactions, and organ-specific properties that inform biomimetic material design. We highlight recent advances in 4D SMART systems, including ionic self-healing, pH-, thermal-, hydration-, and magneto-responsive materials, and their roles in mimicking developmental and regenerative processes. This is followed by a comparative overview of these stimuli-responsive material classes, benchmarked against one another, native ECM performance, and clinical translation requirements, revealing persistent gaps in long-term stability, multi-stimuli integration, and regulatory feasibility. Together, these insights provide an interdisciplinary framework for designing adaptive, responsive biomaterials that guide tissue morphogenesis and advance the future of regenerative medicine.

Graphical abstract
Keywords
Biomaterials
Extracellular matrix
Four-dimensional bioprinting
Four-dimensional tissue engineering
Regenerative medicine
Stimuli-responsive materials
Funding
This research was supported by the Commonwealth Health Research Board (236-08-21); the National Institutes of Health, under the National Institute of General Medical Sciences grant (P20GM113126); the American Cancer Society (IRG-22-146-07-IRG); National Institutes of Health, under the National Cancer Institute grant (CA036727), the Nexus of Virology, Immunology, and Bioengineering; the Nebraska Tobacco Settlement Biomedical Research Development Funds; the “Regional Innovation System & Education (RISE)” program, through the Gwangju RISE Center, funded by the Ministry of Education and the Gwangju Metropolitan Government, Republic of Korea (2025-RISE-05-011).
Conflict of interest
Fanben Meng and Daeha Joung serve as the guest editors of this Special Issue, but did not in any way involve in the editorial and peer-review process conducted for this paper, directly or indirectly. Other authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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