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 within hours
The steps 6-12 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 :
Alkali ions (Na+ and Ca2+) on the glass surface rapidly exchange with hydrogen ions from surrounding bodily fluids. The reaction causes hydrolysis of silica groups and induce a local increase of pH and osmotic pressure.
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:
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.
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.
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).
Growth factors adsorb to the surface of Bioglass due to its structural and chemical similarities to hydroxyapatite.
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.
Triggered by M2 macrophage activation, mesenchymal stem cells and osteoprogenitor cells migrate to the Bioglass surface and attach to the HCA layer.
Stem cells and osteoprogenitor cells at the HCA surface differentiate to become osteogenic cells typically present in bone tissue, particularly osteoblasts.
The attached and differentiated osteoblasts generate and deposit extracellular matrix (ECM) components, primarily type I collagen, the main protein component of bone.
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.
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.
Bioglass is important to the field of biomaterials as one of the first completely synthetic materials that seamlessly bonds to bone. It was developed by Larry L. Hench in the late 1960s. The idea for the material came after atalk with Colonel Klinker, who had recently returned to the United States after serving as an Army medical supply officer in Vietnam.
After listening to Dr. Hench’s description of his research, the Colonel asked, “Can you make a material that will survive exposure to the human body?”Klinker then went on to describe the amputations that he had witnessed in Vietnam, which resulted from the body’s rejection of metal and plastic implants. Hench realized that there was a need for a novel material that could form a living bond with tissues in the body.
When Hench returned to Florida, he began to synthesize small rectangles of what he called 45S5 glass. They were implanted in rat femurs at the VA Hospital in Gainesville. Six weeks later, the researchers called Hench asking, “Larry, what are those samples you gave me? They will not come out of the bone. I have pulled on them, I have pushed on them, I have cracked the bone and they are still bonded in place.”
With this first successful experiment, Bioglass was born and the first compositions studied. Hench published his first paper on the subject in 1971 in the Journal of Biomedical Materials Research, and his lab continued to work on the project for the next 10 years with continued funding from the U.S. Army. By the early 21st century, there were over 500 papers published on the topic of bioactive glasses from different laboratories and institutions around the world.
The French material science laboratory MATEIS, hosted in the INSA institution, has developed an expertise in designing and manufacturing Bioglass. Expertise of the world-known scientists led to patents on new formulations of Bioglass. The company Noraker was founded in 2005 to industrialize and develop these new findings on Bioglass. Since then, Noraker continues to collaborate with top Europe universities, to not only restore the functions of the patients, but also fully regenerate the bone. ²
1 – Rahaman, M. “Bioactive glass in tissue engineering”. Acta Biomaterialia. 7: 2355–2373.
2 – Hench, L.L. (December 2006). “The story of Bioglass”. Journal of Materials Science in Medicine. 17: 967–78.
3 – Rabiee, S.M.; Nazparvar, N.; Azizian, M.; Vashaee, D.; Tayebi, L. (July 2015). “Effect of ion substitution on properties of bioactive glasses: A review”. Ceramics International. 41: 7241–7251
4 – Hench, L. L. (July 1998). “Bioceramics”. Journal of the American Ceramic Society.
5 – Roszer, T. “Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms”. Mediators of Inflammation