Viscoelastic Hydrogels Promote Bone Formation in 3D Cell Cultures

Stem cell researchers have devised a viscoelastic hydrogel matrix that encourages stem cells grown in three-dimensional culture to differentiate into bone tissue, which has promising applications in the realm of bone regeneration, growth, and healing.

Viscoelasticity is a molecular rearrangement. When stress is applied to a viscoelastic material such as a polymer, some areas of the material's long polymer chains change positions. This movement or rearrangement is called creep. Polymers remain a solid material even when these parts of their chains are rearranging in order to accompany the stress, and as this occurs, it creates a back stress in the material. When the back stress is the same magnitude as the applied stress, the material no longer creeps. When the original stress is taken away, the accumulated back stresses will cause the polymer to return to its original form. The material creeps, which gives the prefix visco-, and the material fully recovers, which gives the suffix- elasticity.

Investigators at Harvard University (Cambridge, MA, USA) developed hydrogels for three-dimensional culture with different stress relaxation responses. They reported in the November 30, 2015, online edition of the journal Nature Materials that these types of materials enhanced cell spreading, proliferation, and the osteogenic differentiation of mesenchymal stem cells (MSCs) in cultures with gels with faster relaxation rates. Strikingly, MSCs formed a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels. The effects of stress relaxation were mediated by adhesion-ligand binding, actomyosin contractility, and mechanical clustering of adhesion ligands.

"This work both provides new insight into the biology of regeneration, and is allowing us to design materials that actively promote tissue regeneration," said senior author Dr. David Mooney, professor of bioengineering at Harvard University. "In addition to introducing a new concept to the fields of mechanobiology and regenerative medicine, I expect this work will lead to an explosion of new ideas and research to examine how a number of other material mechanical properties influence cell behavior."

The Harvard University Office of Technology Development has filed a patent application and is actively exploring commercial opportunities for the viscoelastic cell culture technology.

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