Cell driven elastomeric particle packing in composite bioinks for engineering and implantation of stable 3D printed structures

Shira Landau; Jennifer Kieda; Ramak Khosravi; Sargol Okhovatian; Kaitlyn Ramsay; Chuan Liu; Amid Shakeri; Yimu Zhao; Karen Shen; Orit Bar-Am; Shulamit Levenberg; Scott Tsai; Milica Radisic

Bioactive Materials (Feb 2025)

Cell driven elastomeric particle packing in composite bioinks for engineering and implantation of stable 3D printed structures

Shira Landau,
Jennifer Kieda,
Ramak Khosravi,
Sargol Okhovatian,
Kaitlyn Ramsay,
Chuan Liu,
Amid Shakeri,
Yimu Zhao,
Karen Shen,
Orit Bar-Am,
Shulamit Levenberg,
Scott Tsai,
Milica Radisic

Affiliations

Shira Landau: University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada; University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; University of Toronto, Terrence Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada
Jennifer Kieda: University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada; University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; University of Toronto, Terrence Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada
Ramak Khosravi: University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC, United States
Sargol Okhovatian: University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada; University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; University of Toronto, Terrence Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada
Kaitlyn Ramsay: University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada; University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; University of Toronto, Terrence Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada
Chuan Liu: University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada; University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; University of Toronto, Terrence Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada
Amid Shakeri: University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada; University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; University of Toronto, Terrence Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada
Yimu Zhao: University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada; University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; University of Toronto, Terrence Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada; Acceleration Consortium, University of Toronto, Toronto, ON, Canada
Karen Shen: University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada; University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; University of Toronto, Terrence Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada
Orit Bar-Am: Faculty of Biomedical Engineering, Technion, Haifa, IL, Israel
Shulamit Levenberg: Faculty of Biomedical Engineering, Technion, Haifa, IL, Israel
Scott Tsai: Toronto Metropolitan University, Department of Mechanical, Industrial, and Mechatronics Engineering, Toronto, ON, Canada; Toronto Metropolitan University and Unity Health Toronto, Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, ON, Canada
Milica Radisic: University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada; University Health Network, Toronto General Hospital Research Institute, Toronto, ON, Canada; University of Toronto, Terrence Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada; University of Toronto, Department of Chemical Engineering and Applied Chemistry, Toronto, ON, Canada; Acceleration Consortium, University of Toronto, Toronto, ON, Canada; Corresponding author. University of Toronto, Institute of Biomedical Engineering, Toronto, ON, Canada.

Journal volume & issue: Vol. 44
pp. 411 – 427

Abstract

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Geometric and structural integrity often deteriorate in 3D printed cell-laden constructs over time due to cellular compaction and hydrogel shrinkage. This study introduces a new approach that synergizes the advantages of cell compatibility of biological hydrogels and mechanical stability of elastomeric polymers for structure fidelity maintenance upon stereolithography and extrusion 3D printing. Enabling this advance is the composite bioink, formulated by integrating elastomeric microparticles from poly(octamethylene maleate (anhydride) citrate) (POMaC) into biologically derived hydrogels (fibrin, gelatin methacryloyl (GelMA), and alginate). The composite bioink enhanced the elasticity and plasticity of the 3D printed constructs, effectively mitigating tissue compaction and swelling. It exhibited a low shear modulus and a rapid crosslinking time, along with a high ultimate compressive strength and resistance to deformation from cellular forces and physical handling; this was attributed to packing and stress dissipation of elastomeric particles, which was confirmed via mathematical modelling. Enhanced functional assembly and stability of human iPSC-derived cardiac tissues and primary vasculature proved the utility of the composite bioink in tissue engineering. In vivo implantation studies revealed that constructs containing POMaC particles exhibited improved resilience against host tissue stress, enhanced angiogenesis, and infiltration of pro-reparative macrophages.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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