Controlled release of rhBMP-2 from nanoparticle-loaded biomimetic graft promotes bone regeneration in a rat spinal fusion model.

With a notable 118% surge in the last two decades, incidences of lumbar spinal fusion procedures in the United States are experiencing a remarkable upward trend. However, the currently available FDA-approved collagen-based Infuse™ spinal fusion bone graft has been associated with serious complications including heterotopic ossification, paralysis, bowel/bladder dysfunction and local inflammation due to the presence of higher doses of recombinant human bone morphogenetic protein (rhBMP-2), a potent osteogenic growth factor. These challenges have heightened the urgent need for novel spinal fusion bone grafts that offer greater fusion rate and superior clinical outcomes without the risk of adverse side effects. To address this, we have developed a novel porous biomimetic bone graft (BioMim) combining a pro-regenerative porcine small intestinal submucosa-derived extracellular matrix (SIS-ECM) with an osteoconductive biphasic mixture of calcium phosphates (60% hydroxyapatite and 40% beta-tricalcium phosphate) in a 3:7 organic-to-inorganic ratio, closely resembling the molecular composition of native bone. When implanted in a clinically translatable rat posterolateral lumbar spinal fusion model, the BioMim graft loaded with 1 μg rhBMP-2 achieved the highest bone regeneration and significantly greater bone volume compared to absorbable collagen sponge (ACS) loaded with the same dose (P = 0.0070), resulting in early bony union at 8 weeks as confirmed by micro-computed tomography (CT) and histological analysis. The graft further incorporates rhBMP-2 encapsulated in ∼100 nm biodegradable nanoparticles fabricated via polyelectrolyte complexation and kinetically-controlled polymer self-assembly, enabling sustained release of the growth factor for up to 50 days. At a low dose of 0.1 μg rhBMP-2, only the nanoparticle-loaded BioMim graft demonstrated significantly increased bone volume (P = 0.0070) compared to the control and improved fusion and palpation scores compared to bulk rhBMP-2 delivery. Histological evidence by H&E and Masson's trichrome further confirms continuous bridging of bone with this biomimetic bone graft with no presence of fibrotic tissue. These findings underscore the promising potential of our novel biomimetic spinal fusion scaffold in advancing spinal fusion surgeries by promoting faster fusion rates and accelerated bone regeneration.