<p>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.<br /><br /></p>.<p>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).<br /><br />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.<br /><br />Mooney and his team decided to mimic the viscoelasticity of living tissue by developing hydrogels with different stress relaxation responses.<br /><br />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.<br /><br />"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).<br /><br />With increased stress relaxation, there was also a decrease in the differentiation into fat cells.<br /><br />"This is the first time we've observed how matrix stress relaxation impacts stem cell differentiation in 3D," he added.<br /><br />The enhanced stress relaxation dramatically increase early osteogenic differentiation.<br /><br />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.<br /><br />"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.<br /><br />It may seem counter intuitive that bone cells need fast-relaxing environments to grow into bone which is very stiff and elastic.<br /><br />However, the team observed that the microenvironment around bone fractures is very similar to the fastest-relaxing hydrogel the team developed in the lab.<br /><br />"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.<br /><br />The findings were published in the journal Nature Materials.<br /></p>
<p>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.<br /><br /></p>.<p>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).<br /><br />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.<br /><br />Mooney and his team decided to mimic the viscoelasticity of living tissue by developing hydrogels with different stress relaxation responses.<br /><br />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.<br /><br />"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).<br /><br />With increased stress relaxation, there was also a decrease in the differentiation into fat cells.<br /><br />"This is the first time we've observed how matrix stress relaxation impacts stem cell differentiation in 3D," he added.<br /><br />The enhanced stress relaxation dramatically increase early osteogenic differentiation.<br /><br />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.<br /><br />"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.<br /><br />It may seem counter intuitive that bone cells need fast-relaxing environments to grow into bone which is very stiff and elastic.<br /><br />However, the team observed that the microenvironment around bone fractures is very similar to the fastest-relaxing hydrogel the team developed in the lab.<br /><br />"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.<br /><br />The findings were published in the journal Nature Materials.<br /></p>