In vivo bioreactor

The in vivo bioreactor (IVB) is a regenerative medicine paradigm where bone is grown in vivo. The IVB has basic elements:

An example of the implementation of the IVB approach was in the engineering of autologous bone by injecting calcium alginate in a sub-periosteal location. The periosteum is a membrane that covers the long bones, jawbone, ribs and the skull. This membrane contains an endogenous population of pluripotent cells called the periosteal cells, which are a type of mesenchymal stem cells (MSC), which reside in the cambium layer, i.e., the side facing the bone. A key step in the procedure is the elevation of the periosteum without damaging the cambium surface and to ensure this a new technique called hydraulic elevation was developed.

The choice of the sub-periosteum site is used because stimulation of the cambium layer using transforming growth factor–beta resulted in enhanced chondrogenesis, i.e., formation of cartilage. In development the formation of bone can either occur via a Cartilage template initially formed by the MSCs that then gets ossified through a process called endochondral ossification or directly from MSC differentiation to bone via a process termed intra-membranous ossification. Upon exposure of the periosteal cells to calcium from the alginate gel, these cells become bone cells and start producing bone matrix through the intra-membranous ossification process, recapitulating all steps of bone matrix deposition. The extension of the IVB paradigm to engineering autologous hyaline cartilage was also recently demonstrated. In this case, agarose is injected and this triggers local hypoxia, which then results in the differentiation of the periosteal MSCs into articular chondrocytes, i.e. cells similar to those found in the joint cartilage. Since this processes occurs in a relative short period of less than two weeks and cartilage can remodel into bone, this approach might provide some advantages in treatment of both cartilage and bone loss. The IVB concept needs to be however realized in humans and this is currently being undertaken.

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