Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Abstract

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix 1 ; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber-based collagen scaffold in a rodent spine fusion model. Thirty-six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 mg rhBMP-2 on ACS (positive control), TrioMatrix 1 , Grafton 1 (Osteotech, Inc., Eatontown, NJ), and DBX 1 (Synthes, Inc., West Chester, PA). Both TrioMatrix 1 and rhBMP-2-treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton 1 , and DBX 1 groups. Notably, the use of TrioMatrix 1 as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP-2 group. T2-weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP-2; this response was significantly reduced with the use of TrioMatrix 1 . Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost-effective bone graft substitute that could be useful in spine fusions where BMP-2 is contraindicated.

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.…”

Biological Substitutes/Extenders for Spinal Arthrodesis

“…[1][2][3] The presence of variability in its use is a refl ection of uncertainty regarding effectiveness and outcomes, and unawareness regarding costs. An evidence-based approach to cost-effective bone graft decision making would consider both cost and outcome, and be guided by the goal of optimizing value.…”

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.…”