Biphasic Calcium Sulfate

Overview

Biphasic Calcium Sulfate is composed of two phases of the well known Calcium Sulfate. Calcium sulfate (CS) features a unique position among all regenerative bone graft substitutes. With more than 100 years of documented clinical success, (Dreesmann 1892, Thomas and Puleo 2008) it has a longer history of clinical use when compared to most currently available biomaterials.

CS is widely recognized as a well-tolerated bone regeneration material. It undergoes virtually complete resorption in vivo and has consistently been considered as highly biocompatible, osteoconductive, and easy to use (Boden, 1999 or more recently by Pietrzak and Ronk, 2000; Ricci et al., 2000; Tay et al., 1999; Thomas et al., 2005; Thomas and Puleo, 2008).

The raw material, medical grade calcium sulfate is clinically used in 2 different forms differing in their individual (crystal) water content and their physicochemical behavior. (Anusavice 2003).

3D Bond™ and Bond Apatite® - Optimized Application Profile for usage in dental and maxillofacial surgery

3D Bond™ and Bond Apatite® represent the next generation of calcium sulfate-derived bone graft materials. They are self-reinforced graft cement based on the concept of using highly pure biphasic Calcium Sulfate (BCS). Using both phases of calcium sulfate (hemihydrate and dehydrate) in a defined granular formulation provides significant advantages, such as improved handling from the materials' moldability as well as accelerated setting capabilities, even if blood and saliva are present. This also makes for easy and safe use in many typical dental indications.

3D Bond™ and Bond Apatite® Features

• Better Application: Moldable cement for facilitated and precise augmentation.
• Faster Regeneration: Optimal graft characteristics for fast and complete vital bone formation.
• Proven & Safe: Well-documented synthetic technology for optimal graft safety and biocompatibility.

3D Bond™ is a graft binder cement made of pure biphasic calcium sulfate (BCS). It is delivered in a syringe containing the granulated powder. After mixing with liquid, 3D Bond™ can be directly injected into the graft site, either as a stand-alone graft or in a mixture with any bone substitute material.

Bond Apatite® is a bone graft cement combining 3D Bond™ with Hydroxyapatite granules.

The BCS matrix feature complete resorption between 4-10 weeks. The slow-resorbing hydroxyapatite granule matrix serves as longer range space maintainer for optimized volume control.

Bond Apatite® is delivered in a specially designed ready-to-use "All in One" syringe containing the granulated powder and physiological saline. Mixing the powder component with the liquid in the driver results in a viscous composite that is suitable for direct injection into the graft site.

The cement property of Bond Apatite® enables the entire graft placement and stabilization to be completed in less than one minute by the 3 short consecutive steps Place-Press-Close.

Indications

3D Bond™ and Bond Apatite® are indicated for use in following indications:

• Socket grafting
• Lateral augmentation
• Sinus lift
• Cyst enucleation
• Periimplantitis
• Full arch reconstruction
• Aesthetic zone
• Zygomatic implant placement

100% Primary Volume Stability - Moldable cement for ideal initial space maintaining function

3D Bond™ and Bond Apatite® are self-reinforced graft binder cement and bone graft cement, respectively, based on the concept of using highly pure biphasic Calcium Sulfate (BCS).

After mixing the BCS derivate with sterile saline, an injectable putty/moldable cement is formed and 3 consecutive steps should be followed: Place -Press -Close. The putty can be easily applied and bond to the bone defect. Due to the cement-like consistency, the defect configuration can be accomplished very precisely.

After a short settling period, the cement hardens in situ to provide a 100% mechanically stable environment for facilitated membrane application (if required) and wound closure.

Due to the material composition, Bond Apatite® is designed as a stand-alone-bone graft material. The combination with an appropriate barrier membrane is optional and might be indicated, especially if high graft resorption is expected.

3D Bond™ can be mixed with any existing bone graft substitute to profit from both the BCS graft binder cement properties as well as from a certain resorption pattern of the individual bone graft substitute material.

The entire graft placement and stabilization is carried out by 3 short consecutive steps: Place-Press-Close

Setting and Application Procedure

After a short settling period, the cement hardens in situ to provide a 100% mechanically stable environment for facilitated membrane application (if required) and wound closure.

Faster Regeneration - Optimal graft characteristics for fast and complete vital bone formation

3D Bond™ and Bond Apatite® feature both micro- (0-10μm) and macroporous (50-500μm) structure paired with a high overall porosity of more than 40%.

These material characteristics are prerequisite for BCS's excellent scaffolding characteristics needed for new bone formation. The micro-pores allow growth factors infiltration, and macro-pores allow osteoblasts infiltration and angiogenesis.

By that, BCS is differentiating significantly from many other synthetic graft materials that usually only barely contain a microporous system.

After implantation, CS binds to the adjacent bone (Coetzee 1980) and features a fast dissolution. It leaves behind calcium phosphate deposits that stimulate new bone growth accompanied by increased neoangiogenesis, both prerequisites for a 100% vital and well-vascularized bone structure. (Ricci 2000, Strocchi 2002, Turri & Dahlin 2014). The rate of new bone formation for CS was shown to be much faster than for many kinds of typical bone graft substitute materials, regardless of their origin. (Turri & Dahlin 2014, Toloue 2012, Collins 2014).

Proven & Safe - Well-documented synthetic technology for optimal graft safety and biocompatibility

Based on a well-documented fully synthetic technology concept – Optimal graft safety and biocompatibility.

The BCS products are based on highly pure medical grade calcium sulfate and represent a synthetic grafting concept without any risk of disease transmission.

After implantation, calcium sulfate is completely dissolved into its component elements naturally found in the body; this makes this bone graft material well tolerated and non-immunogenic. CS is used as a bone substitute material in all medical disciplines for >100 years (Dreesman 1892), and no adverse reactions or failures to heal have been reported in the literature so far. (Thomas and Puleo 2008)

Technology - Biphasic Calcium Sulfate as 2nd generation technological breakthrough in the long history of CS bone regeneration

The first documented use of CS as augmentation material dates back to 1892 reported by Dreesmann to obliterate bone cavities caused by tuberculosis (reviewed by Peltier, 1961; Peltier and Speer, 1981).

Since then, researchers and clinicians have continued to explore the effectiveness of the material in various applications. The long clinical history as an augmentation material was reported and published in thousands of scientific articles during 120 years of research, not only in dental and maxillofacial applications (Coetzee, 1980), furthermore in orthopedic, plastic surgery, oncology, revision arthroplasty and spinal arthrodeses (Bucholz, 2002).

The raw material, medical grade calcium sulfate is clinically used in 2 different forms differing in their individual (crystal) water content: (Anusavice 2003)

a) Calcium sulfate hemihydrate (CaSO4 · ½ H2O), also known as „Plaster of Paris" b) Calcium sulfate dihydrate (CaSO4 · 2 H2O), also known as Gypsum"

When the CS-hemihydrate is mixed with water, it forms a moldable paste (cement) that sets after a certain time interval. By that, the other CS form, the respective dihydrate is formed: CaSO4 · ½H2O + 1½H2O –> CaSO4 · 2H2O

The complete setting process of CS Hemihydrate needs approx. 20 min and is controlled by the formation and growth of CS dihydrate crystals. In an in vivo scenario, proteins and other biological macromolecules may further retard the setting time to up to 200 min. This is impeding the application procedure as well as the clinical performance of a typical dental application significantly. (Ricci 2000)

Although Orsini and co-workers have shown that there is no difference in the bone healing pattern between preset CS dihydrate granules and moldable CS-hemihydrate cement. (Orsini 2004), by using preset CS dihydrate the surgeon loses advantageous handling properties of the moldable cement derivative.

By making use of the biphasic calcium sulfate concept in 3D Bond™ the previous setting issues can be solved: The CS hemihydrate component is controlling the cement consistency and moldability characteristics. The dihydrate component is regulating the setting properties. Using this formulation, the setting process can be reduced from about 20 minutes to 3 minutes, also under in vivo conditions in presence of blood and saliva.

The key performance criteria of CS-derived graft materials that were shown in numerous studies is the fast and effective vital bone formation as a result of the rapid dissolution in vivo. (Thomas and Puleo 2008, Toloue, Dahlin) These characteristics provoke advantageous clinical results in small and well-contained bony defects like extraction socket filling. (Toloue, Guarnieri)

Nevertheless, when the material shall be applied in larger bone defects with less graft containment, the fast dissolution of CS may lead to a lack of stable osteoconductive scaffold after a certain time, thus losing its mechanical properties. (Walsh) By that, the preservation of the augmented graft volume may be compromised over time.

In order to improve the scaffolding properties of calcium sulfate, it has been successfully used with many kinds of other bone grafts. (Stubbs 2004, Urban 2007)

Bond Apatite® is composed of biphasic calcium sulfate and synthetic hydroxyapatite granules. With this formulation, the concept of graft cement can be successfully applied for a wider range of indications.

The BCS affects an injectable graft cement and features fast resorption and new bone formation. The hydroxyapatite granules provide a slow-resorbing osteoconductive scaffold to preserve the augmented volume also over a longer time period.