124. 3D-printed hyperelastic bone® composite scaffolds as bone graft substitutes

Abstract

BACKGROUND CONTEXT Iliac crest bone graft (ICBG) has long been considered the gold standard implant for use in spinal fusion procedures. Due to significant donor site morbidity associated with graft harvest, however, use of ICBG has largely been abandoned in favor of other materials. Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on an absorbable collagen sponge (ACS; Infuse) is an effective bone graft substitute, but the supra-physiologic doses required to achieve fusion are associated with significant adverse clinical outcomes. Ceramic bone graft substitutes show promise for use in spine fusion, but these materials are brittle and insufficiently osteoinductive. In previous work, we developed a flexible, bioactive and growth factor free 3D-printed scaffold composed of hydroxyapatite (HA), demineralized bone matrix (DBM) and a poly lactic-co-glycolide (PLG) binder. After determining the optimal formulation and geometric configuration of this hyperelastic bone composite (HBC), we demonstrated its ability to achieve fusion in a rat model. PURPOSE The purpose of this study was to compare the efficacy of our optimized HBC scaffold to that of rhBMP-2/ACS in a rat posterolateral spine fusion model. STUDY DESIGN/SETTING Pre-clinical. PATIENT SAMPLE Male and female Sprague-Dawley rats, ages 12-16 weeks. OUTCOME MEASURES Radiography, fusion scoring, microCT, biomechanical analysis. METHODS Fifty male and 50 female Sprague-Dawley rats underwent L4-L5 posterolateral fusion and were implanted with either the HBC scaffold or 10 µg rhBMP-2/ACS, n = 25 per sex for each treatment group. Animals were evaluated radiographically at 10 days and eight weeks postoperatively, followed by euthanasia and spine harvest. Spines assessed for fusion were fixed in formalin, and fusion was assessed via manual palpation conducted by three blinded observers. Spines were scored using an established system in which 0 = motion present between segments bilaterally, 1 = no motion present unilaterally, and 2 = no motion bilaterally. Spines with an average score ≥1 were considered successfully fused. A subset of 10 spines/group were frozen in saline and subsequently underwent biomechanics testing to determine fusion mass strength during flexion and extension. RESULTS All spines treated with rhBMP-2/ACS achieved successful fusion (100% fusion rate). Comparatively, 92% of male and 93% of female HBC spines were successfully fused. No statistically significant differences in fusion rates were noted across all groups, and among male rats, there was no statistically significant difference in fusion scores between the rhBMP-2/ACS and HBC treatment groups. However, among female rats, fusion scores were greater in the rhBMP-2/ACS group than the HBC group (p CONCLUSIONS The HBC scaffold demonstrates the capacity to elicit high rates of spine fusion, yielding rates comparable to those generated by rhBMP-2/ACS when implanted in male rats. This material represents a promising alternative to rhBMP-2, and has the potential to eliminate the requirement for and adverse effects of growth factor use. The suboptimal performance of the HBC scaffold relative to rhBMP-2/ACS in female rats represents a significant clinical concern and warrants further investigation. Continued assessment of the biomechanical properties of the HBC scaffold is required to understand and quantify its strength and stability limitations in the setting of noninstrumented posterolateral spine fusion. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.