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How It Works

How It Works

Within tissues are cells that are controlled by and interact with Type I collagen. Many of these connective tissue cells are “attachment activated“. This means that the cells seek out attachment points on the Type I collagen, become attached, and activate the cascade of events leading to bone formation. How the bone graft material responds to these cells is referred to as the mechanism of action. The core elements of this response are:

  • Providing a scaffold for local cells (osteoconduction)
  • Providing instructions to local cells (osteoinduction)
  • Introducing donor cells (osteogenesis)

 

i-FACTOR™ Bone Graft: Mechanism of Action

i-FACTOR Bone Graft is based on the biological activity of the synthetically derived 15-amino acid peptide found naturally in Type I human collagen. This 15-amino acid peptide (P-15) is responsible for the attachment and proliferation of osteogenic cells. These cells have an affinity for and attach to the P-15 found in i-FACTOR Bone Graft in a similar way they would naturally with Type I collagen in bone.

i-FACTOR Bone Graft facilitates and expedites the ingrowth of bone by promoting the migration of mesenchymal stem cells and other progenitor cells from surrounding tissue.

The high affinity between cells and P-15 supports the physiological mechanism of action in which cells bind to the P-15 and “turn on” to perform their genetically programmed job of making bone.

The novel i-FACTOR Bone Graft “Attract, Attach, Activate” mechanism of action enhances the body’s natural bone healing process.

 

What Makes It Works

What Makes It Works

The way a bone grafting technology works depends on many factors including the properties of the graft itself. Whether natural (allograft, simple demineralized bone matrix) or synthetic (hydroxyapatite, calcium phosphate), structure is key to an osteoconductive scaffold providing a suitable workplace for bone forming cells. Resorption time, porosity, and mechanical strength can vary widely in this class of products. An osteoinductive bone graft (rhBMP, formulated DBM) is defined as a material that can induce the differentiation of mesenchymal cells into osteoblasts. Only a bone graft that is preserved with an osteoinductive factor (e.g., members of the transforming growth factor family) can be considered osteoinductive. Where rhBMPs have been engineered to maintain the growth factors, the processing of DBMs causes significant variability in the amount of osteoinductive factors that remain in the final product. A bone graft is considered osteogenic if it contains living osteogenic cells that are able to survive in the host environment. Some would suggest that this only occurs when autogenous bone has been implanted immediately or when a bone graft substitute has been enriched with autogenous cells. Unfortunately, the viability of cells in non-vascularized, processed allogeneic bone grafts (cellular bone matrix) is unknown.

 

i-FACTOR Bone Graft: Pre-Clinical Study

i-FACTOR Bone Graft is a peptide bone matrix (PBM) – a composite bone substitute consisting of a synthetic collagen fragment (P-15) bound to calcium phosphate particles. As an engineered product, P-15 quantity and viability remain consistent from lot to lot.

 

Proof It Works

Proof It Works

Evidence comes in many forms – with personal experience being the most credible. But before personal experience can be gathered, most bone graft materials must be evaluated under the regulation of the FDA. Tissue products (cellular bone matrices and simple allografts) are not required to provide any clinical proof of safety or performance to the FDA. Evidence supporting device products (formulated DBMs and synthetics) must compare favorably in animal studies to a similar bone graft material already on the market. A drug/device combination (peptide bone matrix and rhBMP) is proven in a human clinical trial.

 

i-FACTOR™ Bone Graft: US FDA IDE Pivotal Study

The U.S. FDA IDE pivotal clinical study was a prospective, randomized, multicenter study comparing i-FACTOR Putty to autologous bone (control) in patients with degenerative cervical disc disease who underwent a single-level instrumented anterior discectomy and fusion procedure. Patient enrollment was completed in May 2013 with a total of 319 patients participating in the study. The key study results – Fusion Rates, Neck Disability Index (NDI), Neurological Outcome, and Complication Rates – were assessed at 12 months after surgery. Most of the patients in the study have been followed for up to six years. The one-year results of this study have been published  in the peer-reviewed journal Spine.

 

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i-FACTOR Bone Graft is the only biologic bone graft made of a synthetic small peptide (P-15) bound to an anorganic bone mineral (ABM). This unique combination creates a surface-bound “Attract, Attach, Activate” mechanism of action that enhances the body’s natural bone healing process. Being surface-bound, all cellular activity resulting from P-15 attachment is restricted to the implant surface so bone cannot grow where it doesn’t belong (ectopic bone growth).

i-FACTOR Bone Graft is not a morphogen so, unlike engineered growth factors, the signals sent following P-15 attachment in a bony site only activate cells that are pre-programmed to become osteoblasts.

 

Clinical Evidence

i-FACTOR Peptide Enhanced Bone Graft exhibits superior clinical outcomes compared to autograft (the ‘gold standard’) in anterior cervical discectomy and fusion.

i-FACTOR Peptide Enhanced Bone Graft is statistically superior to autologous bone in facilitating formation of bridging bone inside PLIF cages.

i-FACTOR Peptide Enhanced Bone Graft demonstrates a high fusion rate and clinical improvements  comparable to ALIF using autograft of BMP, but a with superior safety profile and lower cost.

i-FACTOR Peptide Enhanced Bone Graft provides a high level of bone consolidation in challenging long-bone non-union and delayed unions.

i-FACTOR Peptide Enhanced Bone Graft provides a higher rate of fusion in transforaminal lumbar interbody fusion compared to Actifuse and Vitoss.

  • Berg AJ, et al. Transforaminal lumbar interbody fusion rates with Actifuse, i-FACTOR and Vitoss BA synthetic bone grafts, ISASS 2014 Annual Meeting and EFORT 2014 Congress (poster)

i-FACTOR Peptide Enhanced Bone Graft provides reliable fusion in cervical interbody fusion (80% fused and 17% progressing to fusion at 26 weeks follow-up).

  • Berg AJ, et al. Cervical interbody fusion rates with i-FACTOR Peptide Enhanced Bone Graft, ISASS 2014 Annual Meeting and EFORT 2014 Congress (poster)

i-FACTOR Peptide Enhanced Bone Graft restores near normal bone porosity and trabecular orientation in ACDF.

  • Kesteloot G, et al. Three dimensional remodeling of i-FACTOR Peptide Enhanced Bone Graft substitute in cervical fusions, Belgian Society of Neurosurgery 2016 Annual Meeting (poster)

The synthetic P-15 peptide exhibits greater defect fill compared to freeze dried bone allograft and open flap debridement in periodontal osseous defects.

The synthetic P-15 peptide exhibits greater defect fill and superior clinical results compared to anorganic hydroxyapatite bone matrix in periodontal osseous defects.

The synthetic P-15 peptide is effective in the long-term management of infrabony defects after three-year follow-up.

The synthetic P-15 peptide offered significantly improved clinical outcomes compared to open flap debridement.

 

Pre-Clinical Evidence

The synthetic P-15 peptide results in early bone formation and fusion in a pre-clinical spine model.

The synthetic P-15 peptide results in greater tissue volume fraction and thicker trabeculae compared to autograft in the sheep femur.

The synthetic P-15 peptide accelerates bone regeneration in a pre-clinical osteoporotic rat model.

The synthetic P-15 peptide enhances bone formation compared to non-treated anorganic bone (hydroxyapatite) in posterolateral fusion.

  • Axelsen MG, et al. Evaluation of cell binding peptide (P15) with silk fibre enhanced hydroxyapatite bone substitute for posterolateral spinal fusion in sheep, Eurospine 2015 Annual Meeting, Poster #30

The synthetic P-15 peptide results in significantly faster bone formation in pre-clinical long bone defects.

The synthetic P-15 peptide results in significantly faster bone formation in pre-clinical cranial model.

The synthetic P-15 peptide results in more bone growth compared to non-treated anorganic bone mineral (hydroxyapatite) in a rabbit osseous defect.

  • Guerra FA, et al. Small peptide (P-15) bone substitute efficacy in a rabbit cancellous bone model, ORS 2005 Annual Meeting, Poster #0212

The synthetic P-15 peptide results in equivalent fusion rates to autologous bone in an ovine lumbar fusion model.

  • Patel VV, et al. Lumbar spine fusion in an ovine model comparing P-15/BGS to autogenous bone, ORS 2007 Annual Meeting, Poster #1452

The synthetic P-15 peptide results in superior fusion rates compared to autograft in a goat cervical fusion model.

  • Cheng BC, et al. P-15: An osteoconductive protein to enhance healing of interbody cages, ORS 1998 Annual Meeting, Poster #636

The synthetic P-15 peptide results in optimal healing of segmental cortical bone defects in a rat model.

The synthetic P-15 peptide results in enhanced new bone formation in cortical defects in a rabbit model.

The synthetic P-15 peptide results in faster new bone formation in maxillary sinus defects compared to allograft.

The synthetic P-15 peptide enhances fusion in the  demanding periodontal environment.

 

 

Mechanism of Action

Synthetic P-15 peptide is bound to the anorganic bone mineral and ensures bone grows where you want it.

Synthetic P-15 peptide causes stem cell differentiation to viable osteogenic cells.

P-15 increases the number of viable osteogenic cells attached.

The synthetic P-15 peptide in i-FACTOR Bone Graft results in the natural production of alkaline phosphatase and bone morphogenic protein leading to early bone formation.

The synthetic P-15 peptide results in higher expression of alkaline phosphatase (an early marker of cell proliferation) compared to other bone graft substitutes.

The synthetic P-15 peptide enhances bone marrow stromal cell attachment, spreading and alignment and the provision of biomimetic microenvironments for osteoblasts leading to bone formation.

The synthetic P-15 peptide stimulates early bone formation at a significantly higher rate compared to non-treated anorganic bone (hydroxyapatite).

The synthetic (P-15) peptide results in improved cell viability compared to non-treated anorganic bone (hydroxyapatite) and demineralized bone allograft.