User:MTLE4470 grp6 chm/sandbox

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Mechanism of Action:

When implanted, Bioglass 45S5 reacts with the surrounding physiological fluid, causing the formation of a hydroxyl carbonated apatite (HCA) layer at the material surface. The HCA layer has a similar composition to hydroxyapatite, the mineral phase of bone, a quality which allows for strong interaction and integration with bone. The process by which this reaction occurs can be separated into 12 steps. The first 5 steps are related to the Bioglass response to the environment within the body, and occur rapidly at the material surface over several hours. Reaction steps 6-10 detail the reaction of the body to the integration of the biomaterial, and the process of integration with bone. These stages occur over the scale of several weeks or months. The steps are separated as follows :

1. Alkali ions (ex. Na+ and Ca2+) on the glass surface rapidly exchange with hydrogen ions or hydronium from surrounding bodily fluids. The reaction below shows this process, which causes hydrolysis of silica groups. As this occurs, the pH of the solution increases.

Si⎯O⎯Na+ + H+ + OH- → Si⎯OH+ + Na+ (aq) + OH-

2. Due to an increase in the hydroxyl (OH-) concentration at the surface (a result of step 1), a dissolution of the silica glass network occurs, seen by the breaking of Si⎯O⎯Si bonds. Soluble silica is transformed to the form of Si(OH)4 and silanols (Si⎯OH) creation occurs at the material surface. The reaction occurring in this stage is shown below: Si⎯O⎯Si + H20 → Si⎯OH + OH⎯Si

3. The silanol groups at the material surface condense and re-polymerize to form a silica-gel layer at the surface of Bioglass. As a result of the first steps, the surface contains very little alkali content. The condensation reaction is shown below:

Si⎯OH + Si⎯OH → Si⎯O⎯Si

4. Amorphous Ca2+ and PO43- gather at the silica-rich layer (created in step 3) from both the surrounding bodily fluid and the bulk of the Bioglass. This creates a layer composed primarily of CaO⎯P2O5 on top of the silica layer.

5. The CaO⎯P2O5 film created in step 4 incorporates OH- and CO32- from the bodily solution, causing it to crystallize. This layer is called a mixed carbonated hydroxyl apatite (HCA).

6. Growth factors adsorb to the surface of Bioglass due to its structural and chemical similarities to hydroxyapatite.

7. Adsorbed growth factors cause the activation of M2 macrophages. M2 macrophages tend to promote wound healing and the initiate the migration of progenitor cells to an injury site. In contrast, M1 macrophages become activated when a non-biocompatible material is implanted, triggering an inflammatory response.

8. Triggered by M2 macrophage activation, mesenchymal stem cells and osteoprogenitor cells migrate to the Bioglass surface and attach to the HCA layer.

9. Stem cells and osteoprogenitor cells at the HCA surface differentiate to become osteogenic cells typically present in bone tissue, particularly osteoblasts.

10. The attached and differentiated osteoblasts generate and deposit extracellular matrix (ECM) components, primarily type I collagen, the main protein component of bone.

11. The collagen ECM becomes mineralized as normally occurs in native bone. Nanoscale hydroxyapatite crystals form a layered structure with the deposited collagen at the surface of the implant.

12. Following these reactions, bone growth continues as the newly recruited cells continue to function and facilitate tissue growth and repair. The Bioglass implant continues to degrade and be converted to new ECM material.