Technology

Introduction

ApaTech's technology is based on research to engineer the optimum structure and chemistry for a safe, effective bone graft material that closely approximates natural bone, thus providing a biostimulative and osteoconductive scaffold for new bone growth.

This research examined the effect on bone growth of novel chemical formulations of calcium phosphate, the basis of all ceramic synthetic bone graft substitutes. This resulted in a new class of bone graft substitute, based on silicated calcium phosphate, called Actifuse.

The optimal scaffold and surface chemistry of Actifuse facilitates fast and sustained bone growth by combining osteoconductive and biostimulatory activities.

Actifuse

In Actifuse, phosphate groups have been selectively replaced by silicate groups. This creates a material that, in addition to the clinically proven interconnected macro and microporous structural properties, enhances the deposition and function of the proteins involved in bone growth, thus stimulating rapid formation of bone and improving the subsequent organization and strength of the graft/host bone composite structure.

Unlike a number of traditional calcium phosphate based products, Actifuse does not dissolve; it is a ‘smart’ material that responds to individual patients needs, being osteostimulative and steadily and predictably remodeled by cellular action over time, ensuring that sufficient conductive scaffold remains for the duration of new bone growth and its subsequent maturation. TOP

Unique Product Chemistry - Silicate Substituted Calcium Phosphate

Actifuse is a unique bone graft material in which silicate ions have selectively replaced phosphate groups in the calcium phosphate ionic lattice. This silicate substitution creates a material that promotes rapid formation of bone and increases the volume of bone formed in the graft/host bone composite structure. Macro- and microporosity allows newly forming bone and capillary blood vessels to grow throughout the network of interconnecting pores. Unlike many synthetic bone graft products, Actifuse retains its three-dimensional structure until bone repair is achieved. The surface chemistry and nano structural architecture of Actifuse leads to enhanced adsorption of the proteins involved in osteogenesis,1,2 leading to much more rapid and higher quality bone formation than with traditional synthetic bone graft materials. TOP

The Science of silicon

Silicon has been identified at trace levels in immature bone3 and plays a metabolic role in new bone formation4

  • The surface charge5 and ultrastructure6 of calcium phosphate is altered by silicon substitution
  • Non-porous silicon-substituted calcium phosphate enhances biologic response in vivo as compared to hydroxyapatite7

Elevated levels of silicon (up to 1.0% silicon by weight [wt %]) have been shown in mineralizing osteoid.4 In contrast, silicon deficiencies lead to compromised mineralization of long bones.8 TOP

Silicon substituted ceramics

Silicon substituted calcium phosphates clearly show enhanced in vitro and in vivo activity.7

Bone remodeling occurs more rapidly around Actifuse than around an identical non-silicon substituted calcium phosphate 9,10,11

  • The amount of silicon substituted appears to be significant,9,10 with an optimum 0.8 wt%, a figure that correlates well with the 1.0 wt% measured by Carlisle4 which has been shown to optimize the speed of bone repair both in vivo and in vitro9,11
  • Too much silicon, especially soluble silicon in solution has been shown to have negative effects on cell viability12 TOP
  1. Guth K et al. Protein adsorption and early osteoblastic behavior on phase pure hydroxyapatite (HA) and silicon substituted hydroxyapatite (SiHA). European
  2. Rashid N et al. Effect of silicate substitution on the surface charge of hydroxyapatite. 7th World Biomaterials Congress, Sydney, 2004.
  3. Voronkov MG et al. Silicon and life. Zinatne, Riga,2nd ed, 1977.
  4. Carlisle EM. Silicon: a possible factor in bone calcification. Science 1970; 167: 179-280.
  5. Botelho CM et al. Structural analysis of Sisubstituted hydroxyapatite: zeta potential and X-ray photoelectron spectroscopy. J Mat Sci Mat Med 2002; 13: 1123-1127.
  6. Porter AE et al. The structure of the bond between bone and porous silicon-substituted hydroxyapatite bioceramic implants. J Biomaterials Res A 2006: 78A(1): 25-33.
  7. Gibson IR et al. Chemical characterization of silicon-substituted hydroxyapatite. J Biomed Mater Res 1999; 44(4): 422-428.
  8. Schwarz K, Milne DB. Growth-promoting effects of silicon in rats. Nature 1972; 239(5371): 333-334.
  9. Hing KA et al. Effect of silicon level on rate, quality and progression of bone healing within silicate substituted porous hydroxyapatite scaffolds. Biomaterials 2006; 27: 5014-5026.
  10. Porter AE et al. Ultrastructural comparison of dissolution and apatite precipitation on hydroxyapatite and silicon-substituted hydroxyapatite in vitro and in vivo. J Biomed Mater Res A 2004; 69(4): 670-679.
  11. Hing KA et al. Variation in the rate of bone apposition within porous hydroxyapatite and tricalcium phosphate bone graft substitutes. Trans. 50th A. Meeting Orthopaedic Research Society, San Francisco, CA. 2004b; vol. 29, poster 1038. Rosemont, IL: Orthopaedic Research Society.
  12. Gough JE, et al (2004). Osteoblast responses to tape-cast and sintered bioactive glass ceramics