There has been considerable progress in engineering cardiac scaffolds for the treatment of myocardial infarction (MI). However, it is still challenging to replicate the structural specificity and variability of cardiac tissues using traditional bioengineering approaches. In this study, a four-dimensional (4D) cardiac patch with physiological adaptability has been printed by beam-scanning stereolithography. By combining a unique 4D self-morphing capacity with expandable microstructure, the specific design has been shown to improve both the biomechanical properties of the patches themselves and the dynamic integration of the patch with the beating heart. Our results demonstrate improved vascularization and cardiomyocyte maturation in vitro under physiologically relevant mechanical stimulation, as well as increased cell engraftment and vascular supply in a murine chronic MI model. This work not only potentially provides an effective treatment method for MI but also contributes a cutting-edge methodology to enhance the structural design of complex tissues for organ regeneration.
As an innovative additive manufacturing
process, 4D printing can
be utilized to generate predesigned, self-assembly structures which
can actuate time-dependent, and dynamic shape-changes. Compared to
other manufacturing techniques used for tissue engineering purposes,
4D printing has the advantage of being able to fabricate reprogrammable
dynamic tissue constructs that can promote uniform cellular growth
and distribution. For this study, a digital light processing (DLP)-based
printing technique was developed to fabricate 4D near-infrared (NIR)
light-sensitive cardiac constructs with highly aligned microstructure
and adjustable curvature. As the curvature of the heart is varied
across its surface, the 4D cardiac constructs can change their shape
on-demand to mimic and recreate the curved topology of myocardial
tissue for seamless integration. To mimic the aligned structure of
the human myocardium and to achieve the 4D shape change, a NIR light-sensitive
4D ink material, consisting of a shape memory polymer and graphene,
was created to fabricate microgroove arrays with different widths.
The results of our study illustrate that our innovative NIR-responsive
4D constructs exhibit the capacity to actuate a dynamic and remotely
controllable spatiotemporal transformation. Furthermore, the optimal
microgroove width was discovered via culturing human induced pluripotent
stem cell-derived cardiomyocytes and mesenchymal stem cells onto the
constructs’ surface and analyzing both their cellular morphology
and alignment. The cell proliferation profiles and differentiation
of tricultured human-induced pluripotent stem cell-derived cardiomyocytes,
mesenchymal stem cells, and endothelial cells, on the printed constructs,
were also studied using a Cell Counting Kit-8 and immunostaining.
Our results demonstrate a uniform distribution of aligned cells and
excellent myocardial maturation on our 4D curved cardiac constructs.
This study not only provides an efficient method for manufacturing
curved tissue architectures with uniform cell distributions, but also
extends the potential applications of 4D printing for tissue regeneration.
Cancer metastases are a challenge for cancer treatment due to their organ specificity and pathophysiological complexity. Engineering 3D in vitro models capable of replicating native cancer dissemination can significantly improve the understanding of cancer biology and can help to guide the development of more effective treatments. In order to better mimic the behavior of native cancer, a triculture metastatic model is created using a stereolithography printing technique with optimized inks for investigating the invasion of breast cancer (BrCa) cells into vascularized bone tissue. The printed system allows to study transendothelial migration and the colony‐forming behavior of metastatic BrCa cells. The key steps of BrCa cell progression including expansion, migration, and colonization are continuously monitored and the interactions between cancer cells, vascular cells, and bone cells are systematically investigated. The study results demonstrate that the 3D printed tissue construct by incorporating multiple cells and various favorable ink matrices provides a suitable model to study the interaction between these cells in a complex vascular microenvironment. As such, the 3D printed tricultured model may serve as a valuable tool for studying metastatic breast cancer progression in bone.
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