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Cell Contractile Forces Drive Spatiotemporal Morphogenesis in 4D Bioprinted Living Constructs.
Aixiang Ding1, David S Cleveland1, Kaelyn L Gasvoda1
1Richard and Loan Hill Department of Biomedical Engineering, University of Illinois at Chicago, 909 S. Wolcott Ave., Chicago, IL, 60612, USA.
Matter
|September 18, 2025
Summary
This study introduces a novel 4D bioprinting method using cell-contractile forces as an internal stimulus. This approach enables the creation of complex, cell-laden structures with enhanced biocompatibility and biomimicry for tissue engineering applications.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Bioprinting
Background:
- Current 4D materials often require external stimuli (heat, light), limiting biocompatibility.
- Cell-contractile forces (CCFs) offer a promising internal stimulus for 4D material actuation.
Purpose of the Study:
- Develop a novel bioink for free-standing 4D bioprinting driven by CCFs.
- Investigate simultaneous shape change and cell differentiation in 4D constructs.
- Achieve complex geometric transformations in bioprinted tissues.
Main Methods:
- Fabrication of a composite bioink using oxidized and methacrylated alginate (OMA), methacrylated gelatin (GelMA), and gelatin microspheres.
- Creation of bilayer constructs (cell-free and cell-laden layers) for directed shape change.
- Encapsulation of human mesenchymal stem cells (hMSCs) to drive 4D transformations and differentiation.
- Patterning of individual layers to achieve complex, multi-axis geometric changes.
Main Results:
- Successfully demonstrated free-standing 4D bioprinting using CCFs as the internal stimulus.
- Achieved simultaneous induction of shape change and chondrogenic/osteogenic differentiation in hMSC-laden constructs.
- Engineered complex geometries, including bending around non-parallel axes, through precise layer patterning.
Conclusions:
- CCF-driven 4D bioprinting offers a biocompatible alternative to external stimuli.
- This method enables the creation of sophisticated 4D constructs with potential for advanced tissue regeneration.
- The approach enhances in vitro biomimicry of natural biological 4D processes.
