Augmentation of osseous phenotypes in vivo with a synthetic peptide

Abstract

ABSTRACT:The synthetic peptide B2A2-K-NS augmented the in vitro expression of osseous phenotypes when cells were stimulated with BMP-2, an osteoinductive growth factor. B2A2-K-NS significantly enhanced the effects of BMP-2-induced alkaline phosphatase activity and mineralization. In the absence of BMP-2, B2A2-K-NS did not have an effect on these endpoints. Based on these observations, in vivo studies were conducted to evaluate if B2A2-K-NS could augment osseous phenotypes in an osteoinductive environment in which BMP-2 should be present. In one study, human demineralized bone matrix (DBM) was used to generate an osteoinductive environment and the effects of B2A2-K-NS on ectopic mineralization of subcutaneous implants evaluated. In the second study, a noncritical sized defect in rabbit ulnas with inherent reparative capacity was used as the osteoinductive environment and was treated with or without B2A2-K-NS. In the DBM studies, B2A2-K-NS augmented mineralization as determined using a combination of radiographic analysis and von Kossa staining at 4 weeks postimplant. In the rabbit ulna model, B2A2-K-NS significantly increased the radiographic bone density in the defects compared to carrier-only or no-treatment controls after 6 weeks. Histological staining confirmed that B2A2-K-NS generated a pronounced bone repair response. The results are consistent with the hypothesis that B2A2-K-NS augments osseous phenotypes in an osteoinductive environment, and suggests that B2A2-K-NS may have clinical utility. ß

B2A Peptide on Ceramic Granules Enhance Posterolateral Spinal Fusion in Rabbits Compared With Autograft

“…The finding that B2A/granules enhanced spine fusion is consistent with a previous investigation wherein B2A enhanced long bone repair in vivo, 16 and is consistent with the proposed mechanism of action for B2A. B2A peptides seem to have a unique mechanism of action that is mediated only in osteopromotive environments where osteopromotive signals, such as BMP-2, are produced.…”

“…Recently, peptides that could participate in bone repair have been described including TP508, 14 73-92 15 (a sequence derived from BMP-2), and B2A2 peptides, 16,17 including B2A2-K-NS (B2A). B2A is a synthetic, receptor-targeted peptide 16 that amplifies the biologic response to BMP-2.…”

“…17 In rabbit tibial defects for example, B2A accelerated bone repair. 16 If synthetic peptides such as B2A could be successfully used in spinal fusion procedures, they could potentially moderate fusion rates, change cost to the patient, and decrease morbidity associated with traditional iliac crest harvest. The results of the present study suggest that B2A on a ceramic granular carrier augments spinal fusion in rabbits.…”

“…B2A is a synthetic, receptor-targeted peptide 16 that amplifies the biologic response to BMP-2. The mode of action for B2A peptides apparently involves binding to BMPR-I receptors and, in the presence of BMP-2, a cooperative enhancement of phosphorylation of Smads proteins leading to osteoblastic differentiation.…”

Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

“…These shorter peptide sequences still activate the growth factor receptors, but are smaller molecules that can easily be modified with chemical groups to control their presentation. A number of BMP-2 mimicking peptide sequences have been used to stimulate osteogenic behavior in vitro [65, 66] and in vivo [65, 67, 68]. Peptide sequences that mimic other growth factors important for bone formation, such as analogues for FGF-2 [69] and VEGF [70], have also been identified and shown to have bioactivity.…”