Actifuse™ - A New Class of Synthetic BoneGraft. Unique chemistry facilitates rapid bone growth.

FOXBOROUGH, Mass., – April 06, 2005 – Orthopaedic surgeons now have a unique synthetic bone graft material intended for use as a bone void filler. Actifuse™ offers rapid bone in-growth, superior handling properties, and workability — in addition to the disease-free advantage of a synthetic material. Actifuse, which recently met the requirements of the Food and Drug Administration for marketing in the United States, is a new class of synthetic bone graft material from ApaTech, Inc. and will be featured atthe Spring meeting of the North American Spine Society in Bal Harbor, Florida (April7-9, 2005).

Actifuse is a phase-pure 80 percent porous calcium phosphate material in which certain phosphate groups are selectively replaced with silicate ions. Studies have shown that silicon, as a dietary trace element, plays a significant role in healthy bone formation and remodeling. Silicon is also reported to enhance deposition of bone forming proteins,osteoblastic differentiation, and to stimulate the rapid formation of bone tissue.

Compared to standard calcium phosphate bone void fillers, silicate substituted Actifuse increases the volume of bone formed in the graft/host bone composite structure. The combination of macro- and microporosity offered by Actifuse allows newly forming bone to grow throughout the network of interconnecting pores. Unlike many synthetic bonegraft products, Actifuse retains its three-dimensional structure until bone repair is achieved, with the graft material being biologically remodeled over time.

Distinct from allograft and demineralised bone matrix (cadaveric bone), Actifuse is completely synthetic and supplied sterile to the surgeon. As a result, it is free of pathogens. This means that there is virtually no risk of infection due to human or animal infective agents and no propensity for an immunological reaction to the graft material.

Although autograft is considered to be the “gold standard,” of bone graft materials, it has several shortcomings. For example, because the graft tissue is taken from the patient’s own body, the amount that can safely be harvested from the host is limited. It increases surgery and patient recovery time. Complication rates as high as 49 percenthave been reported. These have included chronic pain, infection, pelvic fractures, and wound drainage, as well as nerve and vascular damage.

As a synthetic material, Actifuse provides surgeons with a safe and effective alternative to both autograft and allograft.

“Actifuse is a significant advance in the technology of synthetic bone grafts,” said SteveCzick, president of ApaTech, Inc., “Its unique combination of an osteo-conductivestructure with exceptional chemical properties provides rapid and high volume bonein-growth, that leads to stable, integrated bone repair.

“Actifuse has a number of superior features compared to existing synthetic graftmaterials and to allograft and autograft. We believe these features will offer superiorperformance to the surgeon and at the recent American Academy of OrthopedicSurgeons meeting, the number of surgeons who committed to trying Actifuse exceededour expectations. We are very pleased with the enthusiasm Actifuse has generated todate,” Czick added.

Actifuse

Actifuse is a new class of synthetic bone graft from ApaTech. Combining an optimized osteoconductive scaffold with unique chemical properties, Actifuse creates the optimal synthetic graft for facilitating rapid and sustained bone ingrowth.

A Unique Product Chemistry - Silicate Substituted Calcium Phosphate .

ApaTech research has focused on uniting an optimized physical scaffold with a novel chemical formulation to manufacture an optimized synthetic bone graft. The result of this extensive research is Actifuse, a new class of synthetic bone graft.Actifuse is a unique bone graft material in which silicate ions have selectively replaced phosphate groups in the calcium phosphate 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 Effect of Silicate on Bone Formation

Actifuse is a phase-pure 80% porous calcium phosphate material in which the phosphate groups are selectively replaced with silicate ions. Studies have shown that silicon is a significant dietary trace element for healthy bone formation and remodeling. Silicon, released in vivo, is reported to enhance osteoblastic differentiation and stimulate the formation of bone tissue. Moreover the surface chemistry of Actifuse leads to enhanced adsorption and activation of the proteins involved in osteogenesis, leading to much more rapid and better quality bone formation than with traditional synthetic bone graft materials.

Exceptional Bone Growth Speed and Volume

The presence of silicate in the Actifuse lattice structure enhances the speed and volume of bone ingrowth. Studies have shown that Actifuse, with its silicate substituted chemistry, forms mature lamellar bone at earlier time points than traditional synthetic bone graft substitutes. Furthermore, histology of the Actifuse implant shows extensive remodeling of the new trabecular network, thus improving the organization and strength of the host bone/graft composite structure.

Actifuse Outperforms ?-TCP and Traditional Hydroxyapatite Synthetic BoneGraft Materials

Research data shows that Actifuse outperforms traditional hydroxyapatite and?-tri-calcium phosphate scaffolds in terms of the rate of new bone formation, the quantity of bone developed, and its quality. Although autograft is a common source of bone graft, and generally considered the “Gold Standard” among bone graft materials, it is associated with a number of clinical issues, including donor site pain and complications. Actifuse provides surgeons with a safe alternative to autograft.

Actifuse Matches Autograft

Autograft is a common source of bone graft, and generally considered the “GoldStandard” among bone graft materials. However it is associated with a number of clinical issues, including donor site pain and complications. Actifuse, when tested in a standard pre-clinical model of spinal fusion, demonstrated equivalence on all parameters, including fusion mass, biomechanical performance and radiographic evidence of fusion, to autograft. Thus Actifuse may provide surgeons with a safealternative to autograft.

Optimal Handling and Placement

The unique granular structure of Actifuse, when combined with localized blood or incombination with blood marrow aspirate, in a ration of 1-1.5:1 (blood/BMA to Actifuse) allows for optimal handling and placement characteristics. Actifuse is a chemically unified implant that acts within the defect site, addressing concerns about possible remote effects associated with bioactive agents.

Sterile, Synthetic, Disease-free.

Actifuse is completely synthetic and therefore free of human pathogens. This means that there is zero risk from infection due to inadvertent transfer of human or animal infective agents, such as HIV, hepatitis, and CJD. Sterility is ensured by time-tested medical product irradiation processes.

Indications for Use: Europe & Australia

Bone graft substitutes are intended to be used in place of cortico-cancellous, or cancellous allograft or autograft bone. The mechanical environment for such uses experiences either low load requirements or compression. Typical surgical applications for bone graft substitutes are: Small void filling, e.g. after removal of a small bone tumour or following bone fracture reduction or in osteotomies and plastic surgery. Spinal fusion, where a cage or screw fixation device is used to relieve the graft site from physiological loads. It is not intended to be used in place of cortical strut allograft bone where high tensile,torsion and/or bending strength are required.

Indications for Use: United States

Actifuse is a bone void filler intended only for orthopaedic applications as a filler forgaps and voids that are not intrinsic to the stability of the bony structure. Actifuse is indicated to be packed gently into bony voids or gaps of the skeletal system, i.e., extremities, spine, and pelvis. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. The product provides a bone void filler that resorbs and is replaced by bone during the healing process.