AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025210205
REVIEW ARTICLE

Advances in decellularized extracellular matrix bioinks for regenerative medicine applications

Jugal Kishore Bupesh Raja1,2 Giselle Y. Díaz3 Fynn S. Owen La Boucan4 Madeleine A. Perry3 Sravya Tekumalla3,5* Tharaka Srinatha Dunuwilla6 Venkatagiri Krishnamoorthy Bupesh Raja7 Stephanie M. Willerth3,5,7,8,9,10*
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1 Faculty of Medicine, Georgian National University SEU, Tbilisi, Georgia.
2 Laboratory of Neuron Ultrastructure and Nanoarchitecture, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia
3 Department of Mechanical Engineering, Faculty of Engineering and Computer Science, University of Victoria, Victoria, British Columbia, Canada
4 Department of Biology, Faculty of Science, University of Victoria, Victoria, British Columbia, Canada
5 Center for Advanced Materials and Technology, University of Victoria, Victoria, British Columbia, Canada
6 Department of Medicine, International Medical School, Alte University, Tbilisi, Georgia
7 Department of Automobile Engineering, School of Mechanical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
8 Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
9 Axolotl Biosciences, Victoria, British Columbia, Canada
10 School of Biomedical Engineering, Faculty of Applied Science, University of British Columbia, Vancouver, British Columbia, Canada
Received: 20 May 2025 | Accepted: 7 July 2025 | Published online: 9 July 2025
(This article belongs to the Special Issue Advances in 3D Bioprinting)
© 2025 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/ )
Abstract

Organ transplantation serves as a critical life-saving intervention. However, the persistent global shortage of donor organs continues to result in high mortality rates. This pressing clinical challenge has fueled the search for alternative therapeutic strategies. Among these strategies, three-dimensional (3D) bioprinting has emerged as a transformative technology capable of fabricating complex tissue constructs using bioinks composed of living cells and supportive biomaterials. Notably, recent advancements have highlighted the incorporation of decellularized extracellular matrix (dECM) as a bioactive component, significantly enhancing biocompatibility, structural integrity, cellular support, and the formation and maturation of vascular networks. In this review, we detail the pivotal role of the ECM as a dynamic reservoir of biochemical signals and mechanical cues that regulate cellular behavior through mechanotransduction. These processes guide essential functions including gene expression, tissue development, and remodeling, thereby ensuring tissue-specific mechanical properties such as elasticity and tensile strength. We highlight how dECM-based bioinks can retain the native structural and molecular features of the ECM, making them ideal for replicating physiologically relevant microenvironments. Representative studies demonstrate the successful application of dECM bioinks in engineering complex in vitro 3D tissue models. Furthermore, we address current challenges in tissue engineering, including the standardization of bioink formulations, the refinement of decellularization techniques, and the enhancement of the mechanical and architectural properties of scaffolds. Finally, we explore emerging solutions—such as artificial intelligence-guided optimization, in situ bioprinting, and the development of patient-specific bioinks—as promising avenues to overcome current limitations and drive the clinical translation of 3D-bioprinted tissues.

Graphical abstract
Keywords
Decellularized extracellular matrix
Decellularized extracellular matrix-based bioinks
Regenerative medicine
Three-dimensional bioprinting
Tissue regeneration
Vascularization
Funding
This study was supported by the NSERC Discovery grant program (No. RGPIN-2017-04044), the NSERC Alliance grant program (No. 590667-2023), the NSERC CREATE training grant in 3D Printing Technology and Materials (No. 565179-2022), the CIHR Project grant program (No. 460840), and the B.C. Ministry of Forests, New Frontiers in Research Fund, Transformation Grant, “Mend the Gap” (No. NFRFT-2020-00238), and the Nanotherapeutics cluster at the University of Victoria.
Conflict of interest
Dr. Willerth is the C.E.O. and co-founder of Axolotl Biosciences, a biotechnology company that sells novel bioinks. The rest of the 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