Journal
BIOMATERIALS
Volume 269, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120607
Keywords
Mesenchymal stromal cells; Spheroids; Alginate; Stress relaxation; Bone regeneration
Funding
- National Institute of Dental and Craniofacial Research of the National Institutes of Health [R01 DE025475, R01 DE025899]
- National Science Foundation Graduate Research Fellowship
- Achievement Rewards for College Scientists (ARCS) Foundation fellowship
- Schwall Dissertation Year fellowship
- NIH Training Grant [T32 GM136559]
- NHLBI Training Program in Basic and Translational Cardiovascular Science [T32 HL086350]
- National Science Foundation
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Research shows that leveraging the mechanical properties of alginate hydrogels can enhance the osteogenic potential of entrapped MSC spheroids. Compared to elastic alginate, calcium deposition of MSC spheroids was increased in ionically crosslinked, viscoelastic hydrogels.
Mesenchymal stromal cells (MSCs) can promote tissue repair in regenerative medicine, and their therapeutic potential is further enhanced via spheroid formation. Stress relaxation of hydrogels has emerged as a potent stimulus to enhance MSC spreading and osteogenic differentiation, but the effect of hydrogel viscoelasticity on MSC spheroids has not been reported. Herein, we describe a materials-based approach to augment the osteogenic potential of entrapped MSC spheroids by leveraging the mechanical properties of alginate hydrogels. Compared to spheroids entrapped in covalently crosslinked elastic alginate, calcium deposition of MSC spheroids was consistently increased in ionically crosslinked, viscoelastic hydrogels. We previously demonstrated that intra-spheroidal presentation of Bone Morphogenetic Protein-2 (BMP-2) on hydroxyapatite (HA) nanoparticles resulted in more spatially uniform MSC osteodifferentiation, providing a method to internally influence spheroid phenotype. In these studies, we observed significant increases in calcium deposition by MSC spheroids loaded with BMP-2-HA in viscoelastic gels compared to soluble BMP-2, which was greater than spheroids entrapped in all elastic alginate gels. Upon implantation in critically sized calvarial bone defects, bone formation was greater in all animals treated with viscoelastic hydrogels. Increases in bone formation were evident in viscoelastic gels, regardless of the mode of presentation of BMP-2 (i.e., soluble delivery or HA nanoparticles). These studies demonstrate that the dynamic mechanical properties of viscoelastic alginate are an effective strategy to enhance the therapeutic potential of MSC spheroids for bone formation and repair.
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