Hydrogel mechanics are a key driver of bone formation by mesenchymal stromal cell spheroids

Autor: J. Kent Leach, Katherine H. Griffin, Jacklyn Whitehead, Marissa Gionet-Gonzales, Charlotte E. Vorwald, Serena E. Cinque
Rok vydání: 2021
Předmět:
Stromal cell
Mesenchymal stromal cells
Biomedical Engineering
Biophysics
Nanoparticle
Bioengineering
02 engineering and technology
Regenerative Medicine
Regenerative medicine
Article
Viscoelasticity
Biomaterials
03 medical and health sciences
Osteogenesis
Stem Cell Research - Nonembryonic - Human
Spheroids
Cellular
Animals
Stress relaxation
Dental/Oral and Craniofacial Disease
Bone regeneration
030304 developmental biology
0303 health sciences
5.2 Cellular and gene therapies
Chemistry
Alginate
Mesenchymal stem cell
technology
industry
and agriculture
Spheroid
Mesenchymal Stem Cells
Hydrogels
Cell Differentiation
Stem Cell Research
021001 nanoscience & nanotechnology
Mechanics of Materials
Musculoskeletal
embryonic structures
Self-healing hydrogels
Ceramics and Composites
Cellular
Spheroids
Development of treatments and therapeutic interventions
0210 nano-technology
Zdroj: Biomaterials
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2020.120607
Popis: 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 intraspheroidal 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.
Databáze: OpenAIRE
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