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Abstract Recently, 3D bioprinting techniques have been broadly recognized as a promising tool to fabricate functional tissues and organs. The bioink used for 3D bioprinting consists of biological materials and cells. Because of the dominant gravitational force, the suspended cells in the bioink sediment resulting in the accumulation and aggregation of cells. This study primarily focuses on the quantification of cell sedimentation-induced cell aggregation during and after inkjet-based bioprinting. The major conclusions are summarized as follows: (1) as the printing time increases from 0 min to 60 min, the percentage of the cells forming cell aggregates at the bottom of the bioink reservoir increases significantly from 3.6% to 54.5%, indicating a severe cell aggregation challenge in 3D bioprinting, (2) during inkjet-based bioprinting, at the printing time of only 15 min, more than 80% of the cells within the nozzle have formed cell aggregates. Both the individual cells and cell aggregates tend to migrate to the vicinity of the nozzle centerline mainly due to the weak shear-thinning properties of the bioink, and (3) after the bioprinting process, the mean cell number per microsphere increases significantly from 0.38 to 1.05 as printing time increases from 0 min to 15 min. The maximum number of cells encapsulated within one microsphere is ten, and 29.8% of the microspheres with cells encapsulated have contained small or large cell aggregates at the printing time of 15 min.
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This content will become publicly available on August 1, 2026
Four-Dimensional Bioprinting: Harnessing Active Mechanics to Build with Living Inks
Three-dimensional (3D) printing can be beneficial to tissue engineers and the regenerative medicine community because of its potential to rapidly build elaborate 3D structures from cellular and material inks. However, predicting changes to the structure and pattern of printed tissues arising from the mechanical activity of constituent cells is technically and conceptually challenging. This perspective is targeted to scientists and engineers interested in 3D bioprinting, but from the point of view of cells and tissues as mechanically active living materials. The dynamic forces generated by cells present unique challenges compared to conventional manufacturing modalities but also offer profound opportunities through their capacity to self-organize. Consideration of self-organization following 3D printing takes the design and execution of bioprinting into the fourth dimension of cellular activity. We therefore propose a framework for dynamic bioprinting that spatiotemporally guides the underlying biology through reconfigurable material interfaces controlled by 3D printers.
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- Award ID(s):
- 2323731
- PAR ID:
- 10643109
- Publisher / Repository:
- Cold Spring Harbor Laboratory Press
- Date Published:
- Journal Name:
- Cold Spring Harbor Perspectives in Biology
- Volume:
- 17
- Issue:
- 8
- ISSN:
- 1943-0264
- Page Range / eLocation ID:
- a041557
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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