Harvard University John A. Paulson Engineering and Applied Sciences (SEAS), Wyss Institute for Biologically Inspired Engineering (Wyss Institute for Biologically Inspired Engineering) researchers, developed a new, more accurate method to control stem cells into bone cell differentiation. This new technology in bone regeneration, growth and healing, and has broad application prospects. SEAS study by Professor Robert P. Pinkas led the completion published in the recent "Nature Materials".
A cellular microenvironment - the tissue surrounding and connecting the cell's protein and polymer network, influenced by a range of cell behavior, including stem cell differentiation. About a decade, researchers have been able to adjust their stiffness microenvironment to guide Stem cell fate.
Adjust only cellular microenvironment (also known as the extracellular matrix) stiffness is assumed that the environment behave like an elastic material such as rubber. Allowed to deform when pressure is applied on an elastic material, the elastic energy is stored, when the deformation is released material rebound to its original shape, like a rubber band. However, in nature, the extracellular matrix is not flexible, they are viscoelastic. Viscoelastic material, such as chewing gum, when the role of a pressure, over time, will relax the stress and dissipate energy.
Mooney and his team decided to develop different stress through relaxation response hydrogels to mimic living tissue viscoelasticity. After the stem cells when they are placed in this viscoelastic microenvironment, and adjust the speed of the gel to relax, they observed, behavior and differentiation of the cells changed dramatically.
Co-first author of this article, Mooney laboratory postdoctoral Luo Gu said: "We found that as stress increases, particularly increased binding hydrogel stiffness, increase differentiation into bone cells with stress relaxation, stem cells into fat cells. The differentiation is reduced. This is the first time we observed in three dimensions, the matrix stress relaxation on the impact stem cell differentiation. "
Increase stress relaxation not only a significant increase in the early differentiation of osteoblasts, and after the initial differentiation of these cells, they continue to grow into bone cells, and the formation of an interconnected, collagen-rich mineralized matrix, which is the bone of bone structural features. Mooney said: "This work not only for Regenerative Biology offers new insights, but also allows us to design some kind of material, and actively promote tissue regeneration."
Co-first author of this article, Mooney former postdoctoral laboratory Ovijit Chaudhuri said the rapid relaxation of the microenvironment could promote more bone formation, and the formation of bone, the reason is that these models may be mechanically reconstruction matrix, easier to change shape.
Chaudhuri said: "Imagine you are trapped in a piece of rubber every move have been rubber elasticity confrontation but if not rubber, but the rubber trapped in the mud, its relaxation stress quickly, is plastic,. You can reshape the putty and move around. In our experiments, we found that the faster stress relaxation allows significantly different cell morphology. "
This seems to violate the "bone cells need to grow fast relaxed environment for the bones" of intuition, because the bone is very hard and elastic. However, the research team observed that fracture the surrounding microenvironment, and the research team in the laboratory developed fast relaxation hydrogel, is very similar.
Gu said: "The solidification of the bone marrow and fracture hematoma, viscoelastic, and rapid stress relaxation performance of this could be an indication that, in the natural environment, when the fracture healing, it requires a very fast stress relaxation matrix. to assist in bone formation. "
The next phase of the study, in vivo testing rapid relaxation of the hydrogel, to explore whether they promote bone healing.
Mooney said: "This will be a new concept introduced into the force field of biology and regenerative medicine, in addition, I hope that it will bring a lot of new research ideas, research how others affect the mechanical properties of cell behavior . "
