1. You use wordings such as “bone growth promotion”, “stimulates new bone formation” and “osteostimulative” when describing BonAlive®. Does this imply osteoinductivity?
No it does not. The existing in vitro and in vivo data shows that BonAlive® acts via osteostimulation and the use of this claim has been authorized in the EU.
2. What are the main beneficial properties of BonAlive® compared to other bone graft substitutes?
Bioactive glasses are materials that are known to increase the activity of osteoblasts to produce new bone while the bioactive glass resorbs away. This process is mediated by the SiO gel surface that is formed on the glass when it dissolves and also the ions that dissolve from the glass when resorbing. Hydroxyapatite is the main mineral in bone, but when used as bone filler it is not participating in producing new bone, it merely is filling a cavity. In addition, BonAlive® provides a bacterial growth inhibiting environment, which is a true benefit in clinical use. The phenomenon is initiated when BonAlive® granules become hydrated (wetted) with a saline solution, which induces a pH rise on the surface of the granules. This, together with the elevated osmotic pressure, has been shown to inhibit bacterial growth with both aerobic and anaerobic bacteria (nearly 50 different bacterial species have been tested). There are many young companies bringing newly developed bioactive bone fillers to the market. However, they typically lack long-term clinical evidence since the products have only recently been developed. BonAlive®, on the other hand, has over 15 years of clinical history, proven performance and safety both in head & neck and orthopaedic surgery.
3. How does BonAlive® differentiate from other bioactive glasses?
In vitro studies have shown that the BonAlive® composition S53P4 gives clearly a better bacterial growth inhibiting response than any of the several other glass compositions tested. When compared to bioactive glass 45S5, the main differences are the glass composition and the time of resorption. In con- trast to 45S5, BonAlive® does not resorb fully within the first 6-12 months but continues to generate new bone actively over a period of several years. This is especially important in older patients that have a tendency to get recurring fractures and in children when bone substitutes resorb too fast, leaving behind empty cavities.
4. What is the scientific explanation for the bacterial growth inhibiting effect?
The bacterial growth inhibiting effect of BonAlive® is based on two simultaneous processes that occur when the granules re act with body fluids. 1) Sodium is released from the surface of the granules, which induces a slight elevation of the pH that is not favourable for the bacteria. 2) The ions (Na, Ca, P and Si) that are released from the surface give rise to an increase in os- motic pressure, i.e. creating an environment where the bacteria cannot grow. Human (higher level cells) cells are capable of protecting themselves from these kinds of external changes but the simple cel- lular structure of bacteria cannot cope with them. Bacteria can develop resistance towards antibiotics (e.g. MRSA) but they cannot develop resistance towards BonAlive®, making it a powerful tool in the local treatment of chronic bone infections.
5. Can BonAlive® be mixed with other materials?
Normally BonAlive® does not need mixing with other materials but the granules should always be hydrated (moistened) with a normal saline solution (0.9% NaCl in sterile water). The granules can also be moistened with the patient’s own blood or bone marrow aspirate. BonAlive® is also an excellent graft extender where BonAlive® granules can be mixed with autograft or allo- graft bone e.g. 50/50 and then implanted.
6. What happens to the filled cavity over time?
The cavity is filled with newly formed bone over time, and BonAlive® granules are gradually replaced by healthy new bone tissue. The resorption rate of the granules is slightly slower than the rate of bone formation which means that no potentially compromising dead or empty spaces form within the cavity due to fast resorption.
7. Are there temperature changes involved when BonAlive® reacts with a fluid (as seen with cements)?
The reactions do not change the temperature of the graft material as seen with many cements when their components are mixed. Hence, the temperature stays the same. BonAlive® is not a cement so the time scale for application also has no limitations in contrast to cements that have to be applied quickly.
8. Is BonAlive® a porous material?
BonAlive® is a solid material. The porosity of the product comes from the space between the individual granules. New bone is initially formed in this intergranular space, which is a clear benefit compared to many synthetic grafts that are not porous enough for bone to be formed within the material. Moreover, the hydroxyapatite layer that forms on the surface of the granules is porous.
9. What are the hydrophilic properties of BonAlive®? Specifically, does it absorb water and expand, or just dissolve in the presence of fluid? And more, does it require osteoclastic activity to resorb?
Bioactive glasses do not expand, and they resorb through surface erosion, not bulk erosion. Osteoclastic activity is not required for the resorption of BonAlive®.
10. How is the use of BonAlive® promoted: stand-alone or hydrated?
The granules should always be hydrated (moistened) either with a normal saline solution, patient’s own blood or bone marrow aspirate.
11. What evidence is there to support the claim of a bacterial growth inhibiting property?
There are in vitro data on the bacterial growth inhibiting property of BonAlive® on a wide range of bacteria. Also there is a significant amount of clinical data on sinus obliteration, mastoid cavity filling and nasal septum perforation repair indications.
12. How do you use BonAlive®?
Before using BonAlive® granules, it is important that:
• All the soft tissue/ infected tissue is thoroughly removed from the defect.
• The granules are moistened with a sterile saline solution to improve the application, to achieve accurate obliteration and to start the bioactive tissue reaction.Special attention must be paid to completely filling the sinus or bone cavity with BonAlive® granules. If necessary, the bone cavity should be covered with e.g. a collagen membrane. When using BonAlive® granules near the joints, special attention must be paid to preventing migration of granules into the joint space. Granules in the joint space could potentially cause wearing of the joints and hamper movement. Granule migration can be prevented by ensuring that a sufficient bone wall pre- exists in the bone defect and by using e.g. fascia or fibrin glue on top of the granules.
13. What are the contraindications of BonAlive®?
BonAlive® granules should not be applied:
• In acute infected tissues.
• To replace structures subject to strong mechanical stress.
• In patients with acute traumatic injuries with open external wounds close to the defect, likely to become infected.
• In patients that have received or are to receive chemo-therapy or radiation therapy at or near the implantation site.
• In patients with known allergy to bioactive glass.
14. What is the biological relevance of the following terms?
• Bioactive: The implant creates interfacial bonding with body tissue in the vicinity.
• Porous: Enables the tissue to grow into the porous.
• Resorbable: Rapid or slow degrading of the implant material thus allowing it to be replaced with body tissue.