MECHANISM OF ACTION OF AUGMENT PRODUCTS

The mechanism of action of all Augment products is dependent on the role of both the matrix and the rhPDGF-BB components.

The matrix component (e.g. β-TCP, collagen) provides the primary mode of action, osteoconduction (the matrix provides a lattice or scaffold for guided bone healing) and mechanical stability of the wound.  Other actions include:

  • Providing a scaffold on which new cells can migrate and attach
  • Filling a defect or void, to prevent collapse of unwanted soft tissues
  • Retaining the rhPDGF-BB solution at the surgical site


The rhPDGF-BB component serves an ancillary function by providing an active stimulus for healing through three significant modes of action:


PDGF Mechanism of Action

1) Chemotaxis
The first step in the repair of damaged tissue is the migration of reparative cells to the site of injury. The process of cell attraction and migration is known as chemotaxis.

As shown by Fiedler (2002), PDGF has a superior ability to recruit mesenchymal cells (cells that are precursors to bone, tendon, ligament and cartilage) relative to other common bone proteins. Values are in units of chemotactic index (CI).

 

2) Mitogenesis
Mitogenesis, also known as proliferation, refers to the process of stimulating cells to divide. Cell division increases the total number of cells and ensures sufficient numbers to provide an adequate healing response. PDGF is a potent mitogen of cells of mesenchymal (musculoskeletal) origin.

In this study from Ozaki (2007) mesenchymal stem cells were separately exposed to multiple growth factors in a study used to assess cell proliferation. The values reported are proportional to the level of cell proliferation. PDGF-BB was the most potent growth factor tested.


 

3) Promotion of Angiogenesis
Regeneration of any tissue is dependent upon the availability of an adequate blood supply. PDGF is directly involved in the regulation of vascular endothelial growth factor (VEGF), a molecule which is critical for stimulating production of new blood vessels (angiogenesis).

As shown by Bouletreau (2002), PDGF directly influences the expression of VEGF (vascular endothelial growth factor) in a dose-dependent manner, a protein necessary for the formation of new blood vessels.
 
Therefore, while the matrix component provides the mechanical function, the ancillary activity of the rhPDGF-BB enhances the response by providing a biological effect.