Researchers have developed a new, more precise way to control the differentiation of stem cells into bone cells which shows promise for bone regeneration, growth and healing.
The problem with only tuning the stiffness of a cell’s microenvironment, also known as the extracellular matrix, is that it assumes the environment behaves like an elastic material (rubber).
But in nature, extracellular matrices are not elastic but viscoelastic like chewing gum that relaxes with stress and dissipates energy over time when a strain is applied.
Mooney 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,” explained Luo Gu, postdoctoral fellow at Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).
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,” he added.
The enhanced stress relaxation dramatically increase early osteogenic differentiation.
These 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 provides new insight into the biology of regeneration and allows us to design materials that actively promote tissue regeneration,” said lead researcher David Mooney, the Robert P Pinkas Family Professor of Bioengineering at SEAS.
It may seem counter intuitive that bone cells need fast-relaxing environments to grow into bone which is very stiff and elastic.
However, the team observed that the microenvironment around bone fractures is very similar to the fastest-relaxing hydrogel the team developed in the lab.
“This may be an indication that in the natural environment, when a bone fracture is healing, it needs a really fast stress relaxation matrix to assist in bone formation,” Gu noted.
The findings were published in the journal Nature Materials.