Novel technique to help grow bone cells

Researchers have developed a new, more precise way to control the differentiation of stem cells into bone cells, an advance that has applications in the realm of bone regeneration, growth and healing.
A cell's microenvironment, the network of proteins and polymers that surrounds and connects cells within tissues, impacts a range of cellular behaviours, including stem cell differentiation.
For about a decade, researchers have been able to direct the fate of stem cells by tuning the stiffness of its microenvironment, also known as the extracellular matrix.
The problem with only tuning stiffness is that it assumes the environment behaves like an elastic material, like rubber.

In nature, extracellular matrices are not elastic, they are viscoelastic like chewing gum.
David Mooney, Professor at Harvard John A Paulson School of Engineering and Applied Sciences (SEAS) and his team decided to mimic the viscoelasticity of living tissue by developing hydrogels with different stress relaxation responses.

When they put stem cells into this viscoelastic microenvironment and tuned the rate at which the gel relaxed, they observed dramatic changes in the behaviour and differentiation of the cells.
"We found that with increasing stress relaxation, especially combined with increased stiffness in the hydrogel, there is an increase of osteogenic - bone cell - differentiation," said Luo Gu, postdoctoral fellow in the Mooney lab and co-first author.

"With increased stress relaxation, there was also a decrease in the differentiation into fat cells. This is the first time we've observed how matrix stress relaxation impacts stem cell differentiation in 3D," said Gu.
Increased stress relaxation dramatically increase early osteogenic differentiation but those cells continued to grow as bone cells weeks after their initial differentiation and formed an interconnected mineralised matrix rich in collagen, key structural features of bone.
"This work both provides new insight into the biology of regeneration, and is allowing us to design materials that actively promote tissue regeneration," said Mooney, who is also a core faculty member of the The Wyss Institute for Biologically Inspired Engineering.

"One reason that fast-relaxing microenvironments promote more osteogenesis and form bone is that cells inside these matrices can mechanically remodel the matrix and more easily change shape, said Ovijit Chaudhuri, former postdoctoral fellow in the Mooney lab and co-first author.
"Imagine being trapped in a block of rubber. Every movement is opposed by the elasticity of the rubber," said Chaudhuri.
"But if instead of rubber you are trapped in Silly Putty, which relaxes stress very quickly and is malleable, you can remodel the putty and move around," he said.
The research was published in the journal Nature Materials.