Stem cell-based treatments for bone injuries have made some remarkable strides in the past few years. Unfortunately, a common pitfall of bone-making stem cells is the tendency of these cells to wander away from the site of injury. This “wander lust” among stem cells can inhibit healing and reduce stem cell efficacy. How to keep the cells home? The answer seems to be encasing them in a water-retaining gel that keeps them in place, but degrades once the cells have done their job.
Cartilage production has benefitted from the use of these so-called “hydrogels” that encase cells and keep them at the site of injury. However, hydrogels have yet to be tried with bone regeneration.
Assistant Professor of Biomedical Engineering, Danielle Benoit, said, “For example, we should not be able to pinpoint repairs within the periosteum, or outer membrane of bone material.”
The hydrogels used by Benoit and her colleagues mimic the body’s natural tissues, but they also are biodegradable and disappear before the immune system recognizes them as foreign substances.
Benoit believes that the special properties of hydrogels could direct bone-making mesenchymal stem cells to make bone mad repair bone fractures at the site of injury, and then leave the site once the cells have completed their mission.
In previous work (M.D. Hoffman, and others, Biomaterials, 34 (35) (2013), pp. 8887–8898), ) Benoit and her co-workers transplanted hydrogel-encased stem cells onto the surface of mouse bone grafts. However, Benoit’s group not only closely observed the behavior of these implanted cells in the animal, but also in culture dishes outside the animal.
In these experiments, Michael Hoffman and others grafted decellularized bone into the long bones of mice. Because these grafts had all their living material removed, all the bone healing that occurred would be solely due to the implanted stem cells.
Then stem cells that had been genetically engineered to glow a fluorescent green color. The bone material was also coated with hydrogels to keep the stem cells at the site of the bone graft. Then Benoit’s group monitored the bone regeneration process to determine the loss or retention of stem cells at the site of the bone graft in the presence or absence of hydrogels. They used the amount of fluorescence to ascertain the number of cells present at the site of repair. Strangely, Benoit and her colleagues were unable to demonstrate the ability of the PEG hydrogels to control spatiotemporal MSC localization. Therefore, it seemed to be due to the hydrogels and their properties.
As it turns out, depending on how the hydrogels are made, they have different rates of degradation. Benoit, therefore, decided to synthesize gel fibers that underwent biodegradation at different rates. Once the hydrogel began to experience degradation, the spaces between the hydrogels fibers increased and this allowed cells to exit the hydrogel.
In a series of experiments Hoffman, Van Hover and Benoit showed that the faster the rates of hydrogels degradation, the poorer the retention of the cells within the hydrogels. Retention rates were directly proportional to the hydrogels rate of degradation, since longer-lived hydrogels showed higher levels of cell retention and shorter-lived gels showed shorter retention times. In the words of Benoit and her colleagues: “cell localization at allograft surfaces decays in close agreement with network degradation kinetics both in vitro and in vivo.
Such hydrogels with variable degradation rates show promise in not only in bone regeneration, but also in heart attacks in which the initiation of healing might be instigated without invasive surgical procedures that can greatly weaken an already incredibly sick patient.