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Macromolecular modulation of a 3D hydrogel construct differentially regulates human stem cell tissue-to-tissue
Diana R Pereira1, Joana Silva-Correia2, Joaquim M Oliveira2
13B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal; CÚRAM SFI Research Centre for Medical Devices, National University of Ireland, Galway, Ireland.
Engineered 3D hydrogels using collagen, hyaluronic acid, and gellan gum create functional tissue interfaces. This approach controls stem cell fate and function for regenerative medicine applications.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Tissue Engineering
Background:
- Creating functional complex tissues requires seamless integration of multiple tissue types.
- The interface between adjacent tissues is critical for overall tissue function.
- Current regenerative medicine strategies face challenges in simultaneous multi-tissue generation and assembly.
Purpose of the Study:
- To engineer differential functional properties in 3D hydrogel constructs by modulating macromolecular composition.
- To investigate the impact of engineered hydrogels on human mesenchymal stem cell (MSC) fate and behavior.
- To create functional tissue-to-tissue interfaces for advanced regenerative applications.
Main Methods:
- Fabrication of two-layered 3D hydrogel constructs using extracellular matrix (ECM)-based materials (collagen type I, hyaluronic acid) and methacrylated gellan gum (GGMA).
- Seeding human mesenchymal stem cells (MSCs) at the interface between the Col I:HA and GGMA hydrogel layers.
- Characterization of acellular and cell-laden constructs for rheological, mechanical, cell viability (Live/Dead staining), apoptosis (flow cytometry), cell proliferation, ECM deposition, phenotype, and paracrine factor secretion.
Main Results:
- Successfully generated 3D hydrogel constructs with distinct layers and a functional tissue-to-tissue interface.
- Demonstrated high MSC viability and no apoptosis induction within the hydrogel constructs.
- Observed controlled MSC self-renewal, maintained MSC phenotype with tunable morphology, and induced differential inflammatory and angiogenic profiles based on the hydrogel microenvironment.
Conclusions:
- Engineered 3D hydrogel constructs can successfully create functional tissue-to-tissue interfaces.
- Modulating macromolecular composition of hydrogels allows for precise control over stem cell behavior and fate.
- These engineered constructs hold potential for multi-tissue regeneration and immune modulation.
