A research team at the University of Illinois, Chicago and the University of Pennsylvania have developed a new and unique technique which uses flexible implantable bone stabilizing plates and stem cells to speed healing of bone defects or large breaks.
This new technique uses stem cells applied at break sites to experience mechanical stress which they do in developing embryos. The forces this creates might help stimulate stem cells to develop into cartilage and bone in addition to encouraging other cell types contained in the bone to regenerate.
Stem cells require environmental cues in order to be able to differentiate into cells which make up unique tissues. Stem cells which give rise to cartilage and bone are subject to mechanical type forces during healing and development.
As bones heal, stem cells contained within the bone marrow near the break site initially become cartilage cells then bone cells which eventually knits together the break. When large gaps between deformed or broken bones occur, adding more stem cells to the break sites can encourage bones to heal faster by either stimulating formation of bone by neighboring cells or by actively participating in the process of regeneration.
However, to use stem cells to regenerate bone, these cells must be delivered to the defect site and then differentiate appropriately for stimulation for repair. The team has developed a unique preparation of these cells which can be manipulated and handled easily for implantation. This supports the cellular differentiation process which occur in embryonic development of bone.
For the preparation, stem cells were cultured to link to each other to form either plugs or sheets. This preparation additionally contained gelatin micro particles which were loaded with growth factors which will help stem cells differentiate. The plugs or sheets can be manipulated and then implanted and thus reduce the tendency for cells to drift away. These materials are called condensates.
In earlier studies, the team used condensates in rodent models to help heal bone defects in their skull. They observed that the condensates remained in place and were able to improve the extent and rate of regeneration of bone.
Recently, they took their idea step further. They developed a unique and flexible fixator. Typically fixators are stiff metal bars or plates which are used to stabilize bones at the break site. These types of fixators reduce the amount of mechanical stress breaks will experience during the healing process.
The flexible fixator would allow the cells in the condensates to experience compressive forces which are critical to stimulating cartilage enhancement and formation of bone.
The team used a rat model for determining how mechanical forces present in bone defects affect the ability of condensates to contribute to formation of bone. When the team used the condensate sheets along with a flexible fixator in the rate models with a femur defect, they observed there was not only enhanced healing but also the bones showed better mechanical function when compared to control rats which had received the condensates and the stiff, more traditional fixators.
The team says the techniques and devices they develop from their research could additionally influence the way physical therapy is implemented after an injury. The findings support regenerative rehabilitation which is an emerging paradigm concept which marries physical therapy principles with regenerative medicine. The goal is to understand how mechanical stimuli will influence the behavior of cells to better impact the outcomes of patients without additional devices or drugs.
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Recapitulating bone development through engineered mesenchymal condensations and mechanical cues for tissue regeneration.