241. Preclinical safety and performance assessment of a novel 3D-printed HA-DBM composite scaffold using a rodent posterolateral fusion model

Abstract

BACKGROUND CONTEXT Historically, autogenous iliac crest bone graft (ICBG) has been considered the gold standard material for spinal fusion. However, the high burden of donor-site morbidity associated with graft harvesting has led clinicians to favor other materials. Notably, INFUSETM – recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered via an absorbable collagen sponge (ACS) – has been shown to yield excellent fusion rates as individual therapy, although its use is associated with significant postoperative inflammation and adverse events. In contrast, most other bone graft substitutes provide insufficient bone regeneration when utilized alone for spinal fusion. Hence, there is a need for novel bone graft substitutes capable of providing adequate osteogenesis with a favorable safety profile. PURPOSE To compare the efficacy and safety profile of previously described 3D-printed HA-DBM composite scaffolds relative to INFUSETM in a rodent L4-L5 posterolateral fusion (PLF) model. STUDY DESIGN/SETTING Preclinical animal model (rat L4-L5 posterolateral spinal fusion model) PATIENT SAMPLE Female Sprague-Dawley rats (age 12-16 weeks) OUTCOME MEASURES Radiographs, fusion scoring, biomechanical testing, MRI quantification of local edema METHODS Fifty Sprague-Dawley rats underwent bilateral L4-L5 posterolateral fusion (PLF), receiving either INFUSETM (10 µg rhBMP-2 on ACS) or HA-DBM composite scaffold. Spines were harvested at 8 weeks postoperation. Fusion was assessed via manual palpation of the samples by three blinded observers. For each sample, a fusion score was determined, wherein 0 = no bridging bone, 1 = unilateral bridging bone, and 2 = bilateral bridging bone. Samples with an average fusion score ≥1 were considered successfully fused. A subpopulation of twenty specimens, 10 INFUSETM and 10 HA-DBM, underwent biomechanical testing to quantify segmental range-of-motion and overall stiffness relative to 8 nonoperated control specimens. An additional 60 animals underwent L4-L5 PLF receiving either ACS only, INFUSETM, or HA-DBM, and were harvested at increasing postoperative time points to undergo lumbar MRI for quantification of soft tissue edema. An additional 90 animals underwent L4-L5 PLF, and various gene and protein expression analyses were used to investigate the pro-osteogenic mechanism of action of the different implant materials. RESULTS Fusion rates were similar between the INFUSETM (100%) and HA-DBM (93%) scaffold groups, although the average fusion score was greater for INFUSETM (2.0± 0.0) relative to HA-DBM (1.5±0.5). Both INFUSETM and HA-DBM treatment resulted in significantly greater stiffness and reduced segmental range-of-motion relative to the nonoperative controls, although these effects were significantly more profound in INFUSETM relative to HA-DBM groups. Both INFUSETM and HA-DBM groups demonstrated significant increases in expression of various pro-osteogenic markers (eg, Alp, Osx, and Runx2). Notably, the INFUSETM group yielded significant edema at both 2- and 5-days postoperation, which was not seen with HA-DBM treatment. CONCLUSIONS The HA-DBM scaffold yielded comparable fusion rates with slightly lower fusion scores and reduced osteoinductivity relative to INFUSETM. However, the exaggerated host inflammatory response seen with INFUSETM was absent in HA-DBM-treated animals. Therefore, the HA-DBM scaffold shows promise as a bone graft substitute with a favorable safety profile. FDA DEVICE/DRUG STATUS rhBMP-2 (INFUSE) [non-human use] (Investigational/Not approved)