Cell Contractile Forces Drive Spatiotemporal Morphing in 4D Bioprinted Living Constructs

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Current 4D materials often require external stimuli (heat, light), limiting biocompatibility.
• Developing intrinsically driven 4D materials is crucial for advanced biomedical applications.

Purpose of the Study:

• To develop a free-standing 4D bioprinting method driven by internal cell-contractile forces (CCF).
• To demonstrate simultaneous shape change and chondrogenic differentiation in cell-laden constructs.
• To achieve complex geometric transformations in 4D bioprinted materials.

Main Methods:

• Fabrication of a composite bioink using oxidized and methacrylated alginate (OMA), methacrylated gelatin (GelMA), and gelatin microspheres.
• Creation of bilayer constructs with cell-free and cell-laden layers to direct shape changes via CCF.
• Encapsulation of human mesenchymal stem cells (hMSCs) to induce differentiation and shape modulation.
• Patterning of individual layers to achieve complex, multi-axial bending.

Main Results:

• Successful free-standing 4D bioprinting driven solely by CCF was achieved.
• Co-induction of shape changes and chondrogenic differentiation in hMSC-laden constructs.
• Demonstration of complex geometric patterning, including bending around non-parallel axes.

Conclusions:

• Cell-contractile forces offer a viable internal stimulus for 4D bioprinting.
• This CCF-mediated approach enhances the biomimicry of biological 4D phenomena in vitro.
• The developed bioink and method hold potential for creating sophisticated, functional tissue constructs.