HoW DOES THE IVB WORK?
The IVB has three basic elements:
(1) Creation of a confined environment in vivo that is adjacent to a tissue locality rich in pluripotent cells,
(2) Injection of a Hydrogel Biomaterial with the appropriate physicochemical and biophysical characteristics in this confined environment so as to predictably alter the signaling environment or trigger a process within this confined environment leading to recapitulation of developmental processes and de novo formation of a functional tissue mass, and
(3) The harvest of the tissue from the confined site and transplantation of this tissue into another site within the patient, leading to a complete autologous tissue engineering strategy.
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 achieve this a new technique called hydraulic elevation was developed*. The choice of the sub-periosteum site was inspired by findings in the literature that stimulation of the cambium layer using transforming growth factor–beta resulted in enhanced Chondrogenesis, i.e., formation of Cartilage.
*Hydraulic Elevation of the Periosteum: A Novel Technique for Periosteal Harvest, Journal of Investigative Surgery, 2004, Vol. 17, No. 4 , Pages 229-233 (doi:10.1080/08941930490472073)
The first example of the successful implementation of the IVB approach was in the engineering of autologous BONE by injecting calcium Alginate in a sub-periosteal location. 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. This is the first and only example of bone tissue engineering with implantation of cells and/or growth factor augmentation to date. This engineered ectopic bone mass was then successfully transplanted in a bone defect within the same animal subject.
The engineering of HYALINE CARTILAGE using the IVB paradigm was recently demonstrated. In this case, Agarose hydrogel 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.
Bone from 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. Since cartilage engineering can be accomplished using the IVB in a relative short period of less than two weeks, 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
(1) Creation of a confined environment in vivo that is adjacent to a tissue locality rich in pluripotent cells,
(2) Injection of a Hydrogel Biomaterial with the appropriate physicochemical and biophysical characteristics in this confined environment so as to predictably alter the signaling environment or trigger a process within this confined environment leading to recapitulation of developmental processes and de novo formation of a functional tissue mass, and
(3) The harvest of the tissue from the confined site and transplantation of this tissue into another site within the patient, leading to a complete autologous tissue engineering strategy.
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 achieve this a new technique called hydraulic elevation was developed*. The choice of the sub-periosteum site was inspired by findings in the literature that stimulation of the cambium layer using transforming growth factor–beta resulted in enhanced Chondrogenesis, i.e., formation of Cartilage.
*Hydraulic Elevation of the Periosteum: A Novel Technique for Periosteal Harvest, Journal of Investigative Surgery, 2004, Vol. 17, No. 4 , Pages 229-233 (doi:10.1080/08941930490472073)
The first example of the successful implementation of the IVB approach was in the engineering of autologous BONE by injecting calcium Alginate in a sub-periosteal location. 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. This is the first and only example of bone tissue engineering with implantation of cells and/or growth factor augmentation to date. This engineered ectopic bone mass was then successfully transplanted in a bone defect within the same animal subject.
The engineering of HYALINE CARTILAGE using the IVB paradigm was recently demonstrated. In this case, Agarose hydrogel 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.
Bone from 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. Since cartilage engineering can be accomplished using the IVB in a relative short period of less than two weeks, 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
