Multifunctional scaffolds for facile implantation, spontaneous fixation, and accelerated long bone regeneration in rodents

Abstract

Self-stiffening, macroporous, shape-memory scaffolds delivering a low dose of osteogenic factors accelerate segmental long bone regeneration in rats. Mending with memory Grafts or osteoconductive scaffolds need to fill large defect volumes to heal critical-size bone defects, but manufacturing and implanting materials to fit snugly within defects can be challenging. Zhang et al. designed compressible macroporous synthetic scaffolds that swelled to their original shape when hydrated (shape-memory). Cylindrical scaffolds implanted into femoral defects in rats delivered a low dose of bone morphogenetic protein while degrading over time to enhance bone formation. Results demonstrate how osteoconductive scaffolds can be engineered to stabilize graft fixation with facile surgical handing, warranting testing in larger animal models. Graft-guided regenerative repair of critical long bone defects achieving facile surgical delivery, stable graft fixation, and timely restoration of biomechanical integrity without excessive biotherapeutics remains challenging. Here, we engineered hydration-induced swelling/stiffening and thermal-responsive shape-memory properties into scalable, three-dimensional–printed amphiphilic degradable polymer-osteoconductive mineral composites as macroporous, non–load-bearing, resorbable synthetic grafts. The distinct physical properties of the grafts enabled straightforward surgical insertion into critical-size rat femoral segmental defects. Grafts rapidly recovered their precompressed shape, stiffening and swelling upon warm saline rinse to result in 100% stable graft fixation. The osteoconductive macroporous grafts guided bone formation throughout the defect as early as 4 weeks after implantation; new bone remodeling correlated with rates of scaffold composition-dependent degradation. A single dose of 400-ng recombinant human bone morphogenetic protein-2/7 heterodimer delivered via the graft accelerated bone regeneration bridging throughout the entire defect by 4 weeks after delivery. Full restoration of torsional integrity and complete scaffold resorption were achieved by 12 to 16 weeks after surgery. This biomaterial platform enables personalized bone regeneration with improved surgical handling, in vivo efficacy and safety.