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Liquefied Microcapsules as Dual-Microcarriers for 3D+3D Bottom-Up Tissue Engineering
Clara R Correia1, Isabel M Bjørge1, Jinfeng Zeng2
1CICECO-Aveiro Institute of Materials, Department of Chemistry, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
Advanced Healthcare Materials
|October 12, 2019
Summary
New liquefied microcapsules overcome hydrogel size limitations for tissue engineering. These novel microcapsules enable 3D+3D bottom-up tissue construction, supporting cell encapsulation and osteogenic differentiation, and promoting vascularization in vivo.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Hydrogel limitations in cell encapsulation due to molecular diffusion constraints.
- Need for larger scaffolds to prevent necrotic cores in engineered tissues.
- Current tissue engineering strategies are limited to microscale architectures.
Purpose of the Study:
- To develop a novel liquefied microcapsule system for overcoming size limitations in cell encapsulation.
- To introduce a 3D+3D bottom-up tissue engineering approach using these microcapsules.
- To evaluate the cell viability, aggregation, osteogenic potential, and in vivo vascularization capacity of the microcapsules.
Main Methods:
- Production of microcapsules via electrohydrodynamic atomization with controlled sizes (average 608.5 ± 122.3 µm).
- Incorporation of arginyl-glycyl-aspartic acid (RGD) domains into the microcapsule membrane.
- Culturing microcapsules alone or on 2D cell beds (HUVECs, fibroblasts) and assessing cell encapsulation (LiveDead, MTS, dsDNA assays).
- Evaluation of macroaggregate formation (F-actin immunofluorescence) and osteogenic differentiation (alkaline phosphatase activity).
- In vivo assessment using the chick chorioallontoic membrane (CAM) model to evaluate vascularization.
Main Results:
- Successfully produced microcapsules with controlled sizes and introduced RGD domains.
- Demonstrated robust cell encapsulation and viability within the microcapsules.
- Observed cell-mediated macroaggregate formation in specific co-culture conditions (microcapsule³).
- Confirmed osteogenic differentiation potential of the microcapsule system.
- Showed comparable vascular recruitment in vivo to basic fibroblast growth factor (bFGF).
Conclusions:
- Liquefied microcapsules offer a scalable solution for cell encapsulation, overcoming limitations of traditional hydrogels.
- The 3D+3D bottom-up approach enables the creation of larger, viable engineered tissue constructs.
- The developed system supports cell survival, promotes tissue self-assembly, and demonstrates potential for bone regeneration and vascularization.

