Researchers at the University of Illinois at Chicago teamed up with researchers from the University of Pennsylvania and Case Western University to investigate probable solutions for bone defects.
Bone development involves multiple steps and processes. The processes are rather complex starting from the differentiation of stem cells into cartilage ones. Although the conversion of cartilage cells into bone is followed by the earlier differentiation, there is another process involved.
For the successful transformation from stem to bone cells the cells must experience stresses. Mechanical stresses are necessary for an efficient transformation.
The findings of the study appear in the journal Science Advances.
The team tested a one-of-its-kind system which could deliver active stem cells to bone defect sites. Further, they then paired it with the manually adjustable stressing machine.
The stressing machine had flexible fixating rods and pins to provide tunable amounts of mechanical stress.
Mimicking the bone formation process
The research team, under the leadership and guidance of EbenAlsberg and Joel Boerckel, devised a way to dictate the working of certain growth factors. Eben serves as a Professor of Bioengineering and Orthopaedics in the University of Illinois Chicago College of Engineering. Joel is an assistant professor of orthopedic surgery at the University of Pennsylvania.
The deliverance of two of these growth factors simulates the same bone formation process that happens during embryonic bone development.
Researchers confirmed their findings after using the rat model to test the model.
Alsberg and Boerckel co-authored the study. The team replicated many conditions necessary for bone growth and repair. Of these the presence of stem cells, the growth factors and specific mechanical stress is absolutely necessary. These steps are the same that nature uses for bone repair.
Previously, Alsberg and a team of researchers had made the flexible fixators and stem cell “condensates”. The condensates consisted of moveable sheets or plugs of the stem cells. These condensates enabled the researchers to place the stem cells in specific areas of the body, such as within bone gaps or defects. The condensates form meant that the risk of floating away was minimized.
The team injected the cell-containing liquids having stem cells in them directly in the body prior to the manufacture of condensates. This gave rise to the problem of floating away.
After the research, the researchers understood that condensates and flexible fixators allowed for enhanced healing of bone defects in a rat model.
Addition of TGF-beta1 and BMP-2
The research tested those rats who had damaged femur bones. During the course of the current research, Alsberg and team added another layer to their system. Firstly, they incorporated multiple growth factors into the condensates. Secondly, they administered condensates including the growth factors in the rats.
The growth factors in the condensates included the transforming growth factor beta1 or TGF-beta1, and also the bone morphogenic protein 2 or BMP-2.
The former helped with the formation of cartilage with the latter assisting the cartilage into a bone.
This helps encourage the growth of new bone with enhanced function at 12 weeks compared with rats where growth factors weren’t included or only a single growth factor was given in the condensate/flexible fixator system.
The research team achieved remarkable bone repair during their trials. They compared the process as effective as the FDA approved tissue engineering product used for spinal fusion. However, while the collagen product can result in uncontrolled bone-formation it was evident from the study that bone only formed in the regions where the growth factor-infused condensates were present.
The team is extremely hopeful that one day the stem cells, flexible fixators and timely secretion of the growth factors would pave a path for the treatment of bone defects.