Mechanism of action

Discover how the novel i-FACTOR™ Bone Graft mechanism of action creates a safe and natural enhancement to the bone healing process.

i-FACTOR Bone Graft is the only biologic bone graft made of a 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.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft is Bound to the Anorganic Bone Matrix and Ensures Bone Grows Where You Want it.

Hole BB, Schwarz JA, Gilbert JL, Atkinson BL. A study of biologically active peptide sequences (P-15) on the surface of an ABM scaffold (PepGen P-15) using AFM and FTIR. J Biomed Mater Res A. 2005 Sep 15;74(4):712-21.

Qian JJ, Bhatnagar RS. Enhanced cell attachment to anorganic bone mineral in the presence of a peptide related to collagen. J Biomed Mater Res. 1996 Aug;31(4):545-54.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Increases the Number of Viable Osteogenic Cells Attached

Qian JJ, Bhatnagar RS. Enhanced cell attachment to anorganic bone mineral in the presence of a peptide related to collagen. J Biomed Mater Res. 1996 Aug;31(4):545-54.

Turhani D, Weissenböck M, Watzinger E, Yerit K, Cvikl B, Ewers R, Thurnher D. In vitro study of adherent mandibular osteoblast-like cells on carrier materials. Int J Oral Maxillofac Surg. 2005 Jul;34(5):543-50. Epub 2005 Jan 26.

Turhani D, Item C, Thurnher D, Kapral D, Cvikl B, Weissenböck M, Yerit K, Erovic B, Moser D, Watzinger F, Ewers R, Lauer G. [Evidence of osteocalcin expression in osteoblast cells of mandibular origin growing on biomaterials with RT-PCR and SDS-PAGE/Western blotting]. Mund Kiefer Gesichtschir. 2003 Sep;7(5):294-300. Epub 2003 Sep 12. German.

Bhatnagar RS, Qian JJ, Wedrychowska A, Sadeghi M, Wu YM, Smith N. Design of biomimetic habitats for tissue engineering with P-15, a peptide analogue of collagen. Tissue Eng. 1999 Feb;5(1):53-65.

Yuan K, Huang JS, Hsu CW, Hung IJ. A mineralization-associated membrane protein plays a role in the biological functions of the peptide-coated bovine hydroxyapatite. J Periodontal Res. 2007 Oct;42(5):420-8.

Mittal A, Negi P, Garkhal K, Verma S, Kumar N. Integration of porosity and bio-functionalization to form a 3D scaffold: cell culture studies and in vitro degradation. Biomed Mater. 2010 Aug;5(4):045001.

The P-15 PEPTIDE In i-FACTOR Peptide Enhanced Bone Graft Causes Stem Cell Differentiation to Viable Osteogenic Cells.

Lauritano D., Carinci F., Zollino I., Hassanipour A., Saggese V., Palmieri A., Girardi A., Cura F., Piras A., Zamboni P., Brunelli G. P15 induces RUNX2 in bone marrow derived stem cells. European Journal of Inflammation (2012) 10:1 Supplement 3 (95-100). 2012.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Results in Increased Expression of Alkaline Phosphatase (an Important Enzyme in the Mineralization Process) Leading to Early Bone Formation.

Nguyen H, Qian JJ, Bhatnagar RS, Li S. Enhanced cell attachment and osteoblastic activity by P-15 peptide-coated matrix in hydrogels. Biochem Biophys Res Commun. 2003 Nov 7;311(1):179-86.

Yang XB, Bhatnagar RS, Li S, Oreffo RO. Biomimetic collagen scaffolds for human bone cell growth and differentiation. Tissue Eng. 2004 Jul-Aug;10(7-8):1148-59.

Hennessy KM, Pollot BE, Clem WC, Phipps MC, Sawyer AA, Culpepper BK, Bellis SL. The effect of collagen I mimetic peptides on mesenchymal stem cell adhesion and differentiation, and on bone formation at hydroxyapatite surfaces. Biomaterials. 2009 Apr;30(10):1898-909.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Results in Increased Expression of Bone Morphogenic Protein (BMP) Leading to Early Bone Formation

Nguyen H, Qian JJ, Bhatnagar RS, Li S. Enhanced cell attachment and osteoblastic activity by P-15 peptide-coated matrix in hydrogels. Biochem Biophys Res Commun. 2003 Nov 7;311(1):179-86.

Yang XB, Bhatnagar RS, Li S, Oreffo RO. Biomimetic collagen scaffolds for human bone cell growth and differentiation. Tissue Eng. 2004 Jul-Aug;10(7-8):1148-59.

Emecen P, Akman AC, Hakki SS, Hakki EE, Demiralp B, Tözüm TF, Nohutcu RM. ABM/P-15 modulates proliferation and mRNA synthesis of growth factors of periodontal ligament cells. Acta Odontol Scand. 2009;67(2):65-73.

The P-15 Peptide in i-FACTOR Peptide-Enhanced Bone Graft is Able to Up- and Down-Regulate Specific Gene Expression Relating to Cell Cycle Regulation, Apoptosis, Structural Protein and Signalling Transduction

Carinci F, Pezzetti F, Volinia S, Laino G, Arcelli D, Caramelli E, Degidi M, Piattelli A. P-15 cell-binding domain derived from collagen: analysis of MG63 osteoblastic-cell response by means of a microarray technology. J Periodontol. 2004 Jan;75(1):66-83.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Stimulates the Immediate and Prolonged Expression of TGF-B1 Growth Factor at Significantly Higher Levels than Hydroxyapatite alone

Trasatti C, Spears R, Gutmann JL, Opperman LA. Increased Tgf-beta1 production by rat osteoblasts in the presence of PepGen P-15 in vitro. J Endod. 2004 Apr;30(4):213-7.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Increases the Expression of TGF-B1 and BMP-2 to Enhanced Tissue Regenerative Capacity

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Stimulates the Expression of RUNX2 and SP7 (Important Transcription Factors Involved in Osteoblast Differentiation and Bone Formation)

Liu Q, Limthongkul W, Sidhu G, Zhang J, Vaccaro A, Shenck R, Hickok N, ShapiroI, Freeman T. Covalent attachment of P15 peptide to titanium surfaces enhances cell attachment, spreading, and osteogenic gene expression. J Orthop Res. 2012 Oct;30(10):1626-33.

The P-15 Peptide in I-FACTOR Peptide Enhanced Bone Graft Stimulates the Expression of FOSL1 (Involved in the Regulation of Bone-Specific Gene Expression Relating to Osteoblast Differentiation).

The P-15 peptide in i-FACTOR Peptide Enhanced Bone Graft Stimulates the Expression of SPP1 and BGLAP (Two Genes Expressed by Osteoblasts During Their Early Differentiation) in Bone Marrow Derived Mesenchymal Stem Cells

Sollazzo V, Palmieri A, Girardi A, Farinella F, Carinci F. Early effects of p-15 on human bone marrow stem cells. J Oral Maxillofac Res. 2010 Apr 1;1(1):e4.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Modulates Gene Expression Relating to Multiple Extracellular Matrix Genes Including COL1A1 and COL3A1.

Sollazzo V, Palmieri A, Girardi A, Farinella F, Carinci F. Early effects of p-15 on human bone marrow stem cells. J Oral Maxillofac Res. 2010 Apr 1;1(1):e4.

The P-15 peptide in i-FACTOR Peptide Enhanced Bone Graft Influences Micro-RNA Expression and Gene Expression in Osteoblast-like Cells.

Palmieri A, Pezzetti F, Brunelli G, Martinelli M, Lo Muzio L, Scarano A, Degidi M, Piattelli A, Carinci F. Peptide-15 changes miRNA expression in osteoblast-like cells. Implant Dent. 2008 Mar;17(1):100-8.

Palmieri A, Pezzetti F, Brunelli G, Zollino I, Scapoli L, Martinelli M, Arlotti M, Carinci F. Differences in osteoblast miRNA induced by cell binding domain of collagen and silicate-based synthetic bone. J Biomed Sci. 2007 Nov;14(6):777-82. Epub 2007 Jul 25.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Stimulate More Rapid Cytoskeletal Development Compared to Untreated Substrates.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Results in Higher Expression of Alkaline Phosphatase (An Early Marker of Cell Proliferation) Compared to Other Bone Graft substitutes.

Kübler A, Neugebauer J, Oh JH, Scheer M, Zöller JE. Growth and proliferation of human osteoblasts on different bone graft substitutes: an in vitro study. Implant Dentistry. 2004 June :13(2) :171-9.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Enhances Bone Marrow Stromal Cell Attachment, Spreading and Alignment, and the Provision of Biomimetic Microenvironments for Osteoblasts Leading to Bone Formation.

Yang XB, Bhatnagar RS, Li S, Oreffo RO. Biomimetic collagen scaffolds for human bone cell growth and differentiation. Tissue Eng. 2004 Jul-Aug;10(7-8):1148-59.

Thorwarth M, Schultze-Mosgau S, Wehrhan F, Kessler P, Srour S, Wiltfang J, Andreas Schlegel K. Bioactivation of an anorganic bone matrix by P-15 peptide for the promotion of early bone formation. Biomaterials. 2005 Oct;26(28):5648-57. Epub 2005 Apr 18.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Stimulates Early Bone Formation at a Significantly Higher Rate Compared to Non-Treated Anorganic bone (Hydroxyapatite).

If you’re interested in reading information on the evidence listed below, click read more.

Thorwarth M, Schultze-Mosgau S, Wehrhan F, Srour S, Wiltfang J, Neukam FW, Schlegel KA. Enhanced bone regeneration with a synthetic cell-binding peptide--in vivo results. Biochem Biophys Res Commun. 2005 Apr 8;329(2):789-95.

Lindley EM, Guerra FA, Krauser JT, Matos SM, Burger EL, Patel VV. Small peptide (P-15) bone substitute efficacy in a rabbit cancellous bone model. J Biomed Mater Res B Appl Biomater. 2010 Aug;94(2):463-8.

The P-15 peptide in i-FACTOR Peptide Enhanced Bone Graft Results in Improved Cell Viability Compared to Non-Treated Anorganic Bone (Hydroxyapatite) and Demineralised Bone Allograft.

Hanks T, Atkinson BL. Comparison of cell viability on anorganic bone matrix with or without P-15 cell binding peptide. Biomaterials. 2004 Aug;25(19):4831-6.

The P-15 Peptide in i-FACTOR Peptide Enhanced Bone Graft Results in Increased Expression of Transforming Growth Factor-B1, Which is Believed to be Important in the Development Induction and Repair of Bone.

Hanks T, Atkinson BL. Comparison of cell viability on anorganic bone matrix with or without P-15 cell binding peptide. Biomaterials. 2004 Aug;25(19):4831-6.

Preclinical

Studies have shown that P-15, in combination with ABM, mimics the behavior of autograft bone. Learn more about the depth of scientific research supporting this novel bone graft.

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Clinical

Research needs to translate into patient outcomes. Learn more about how i-FACTOR is transforming patients lives by providing clinicals with Level-1 data demonstrating the safety and efficacy of this unique category of bone graft

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The proof you require, the safety you demand.

Clinical Superiority

Level 1 data supports your evidence based clinical decision making.

Peptide Power

The only bone graft to harness the intense biological activity of a peptide (P-15).

Ready to use

Store at room temperature. Ready to use without mixing.

Fill and forget

Don’t assume your bone graft will perform.

Tried and trusted

FDA PMA approved (2015) active biologic and has been CE Marked since 2008.

Safety by design

The unique P-15 action is surface bound and unlike growth factors only grows bone where you need it.