Gel Scaffolds of BMP‐2‐Binding Peptide Amphiphile Nanofibers for Spinal Arthrodesis

Abstract

Peptide amphiphile (PA) nanofibers formed by self-assembly can be customized for specific applications in regenerative medicine through the use of molecules that display bioactive signals on their surfaces. We report here on the use of PA nanofibers with binding affinity for the bone promoting growth factor BMP-2 to create a gel scaffold for osteogenesis. With the objective of reducing the amount of BMP-2 used clinically for successful arthrodesis in the spine, we used amounts of growth factor incorporated in the scaffolds that are 10 to 100 times lower than that those used clinically in collagen scaffolds. The efficacy of the bioactive PA system to promote BMP-2-induced osteogenesis in vivo was investigated in a rat posterolateral lumbar intertransverse spinal fusion model. PA nanofiber gels displaying BMP-2-binding segments exhibited superior spinal fusion rates relative to controls, effectively decreasing the required therapeutic dose of BMP-2 by ten-fold. Interestingly, a 42% fusion rate was observed for gels containing the bioactive nanofibers without the use of exogenous BMP-2, suggesting the ability of the nanofiber to recruit endogenous growth factor. Results obtained here demonstrate that bioactive biomaterials with capacity to bind specific growth factors by design are great targets for regenerative medicine.

The effect of vancomycin powder on bone healing in a rat spinal rhBMP-2 model

“…Of note, a negative control group was not used, as ACS alone has previously demonstrated a 0% fusion rate and thus serves as a historical control. 12,18 Radiographic fusion was evaluated 4 and 8 weeks postoperatively. Spines were harvested at 8 weeks and subsequently evaluated using manual palpation fusion scoring, microCT, and histological analysis.…”

“…All harvested spines were manually palpated for evidence of successful fusion by 3 independent, blinded observers using a previously published scoring system, whereby 0 indicates no bridging bone, 1 indicates unilateral bridging, 2 indicates bilateral bridging, and 3 indicates bilateral bridging with abundant bone formation. 12,18 Individual scores for each specimen were then averaged. As with the human patient population, in which unilateral bridging constitutes successful fusion, spines with an average score ≥ 1.0 were considered successfully fused.…”

“…In a modification of a previously published protocol, 2 spines were placed in a plastic holder with the spines' axes parallel to the scanner's ro-tation axis. 12,13,18 The pair of spines was scanned simultaneously using an x-ray voltage tube of 70 kVp and 114 μA, and the integration time for each projection was 0.200 seconds. Reconstruction was performed with 37-mm isotropic volume elements (voxels), and the 540-contiguous slice data sets encompassed the L-4 and L-5 transverse processes.…”

Gasotransmitter delivery via self-assembling peptides: Treating diseases with natural signaling gases

“…Under mineralization conditions, hydroxyapatite crystals grew along the long axes of the nanofibers. Since this first report, substantial research has been done in the field of PAs to explore their self-assembled structure [129,130], develop their ability to deliver drugs [131,132], display bioactive epitopes [133,134], and investigate their potential applications in regenerative medicine [135,136].…”

Editorial: Vancomycin, bone growth, and wound healing

“…3,4,[8][9][10] A paper in this issue of Journal of Neurosurgery: Spine may alleviate some of these fears. Mendoza et al 7 demonstrated that, in a rat spinal fusion model, vancomycin was not inhibitory to bone growth.…”