Growth Factor Research
and Why Growth Factors Have
Performed Poorly in Clinical Trials

BMP-7 (bone morphogenic protein 7)

OP-1(BMP-7) in collagen carrier showed only one out of three sinus augmentations producing enough bone for implant placement after 6 months.

Histomorphometrical analysis of bone formed in human maxillary sinus floor elevations grafted with OP-1 device, demineralized bone matrix or autogenous bone. Comparison with non-grafted sites in a series of case reports.

Groeneveld EH, van den Bergh JP, Holzmann P, ten Bruggenkate CM, Tuinzing DB, Burger EH

BMP-2 (bone morphogenic protein 2)
BMP-2 produced inferior results for sinus augmentation when compared to other graft materials. 21% of sinus lifts failed and implants could not be placed. Of the implants placed, 18% failed within 6 months of loading.

Pivotal, randomized, parallel evaluation of recombinant human bone morphogenetic protein-2/absorbable collagen sponge and autogenous bone graft for maxillary sinus floor augmentation.

Triplett RG, Nevins M, Marx RE, Spagnoli DB, Oates TW, Moy PK, Boyne PJ
BMP-2 stimulates both osteoblasts and osteoclasts
Enhanced osteoclastogenesis causes osteopenia in twisted gastrulation-deficient mice through increased BMP signaling.

Sotillo Rodriguez JE, Mansky KC, Jensen ED, Carlson AE, Schwarz T, Pham L, MacKenzie B, Prasad H, Rohrer MD, Petryk A, Gopalakrishnan R
PDGF (platelet derived growth factor)
PDGF stimulates mesenchymal stem cell proliferation but does not stimulate mesenchymal stem cells toward osteogenic differentiation and also does not stimulate factors involved in osteogenesis.

Platelet-derived growth factor receptor signaling is not involved in osteogenic differentiation of human mesenchymal stem cells.

Kumar A, Salimath B, Stark G, Finkenzeller G
Recombinant Human Platelet-derived Growth Factor (rhPDGF-BB)
PDGF when applied to beta tricalcium phosphate results in no clinical attachment gain over beta tricalcium phosphate alone and equal bone regeneration after 3 years.

Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial.

Nevins M, Giannobile WV, McGuire MK, Kao RT, Mellonig JT, Hinrichs JE, McAllister BS, Murphy KS, McClain PK, Nevins ML, Paquette DW, Han TJ, Reddy MS, Lavin PT, Genco RJ, Lynch SE
Why Growth Factors Perform Poorly in Clinical Trials
  • Growth factor half-life in intercellular fluid is between seconds to minutes depending on the growth factor.
  • Cell membrane receptors for growth factors are limited, therefore, applying additional growth factor molecules will not increase cell response.
  • Creating a tissue requires a very large number of molecules to be present at a specific time, concentration, and sequence to create normal tissue. A single growth factor is a very minor part of a regenerating tissue.
  • Due to immune reaction to the foreign growth factor, many growth factors can only be used one time in a patient and cannot be used if pregnant or will become pregnant within one year.

    American Society for Bone and Mineral Research (ASBMR)

    Tissue Engineering and Regenerative Medicine International Society (TERMIS)