Nanoclay gels attenuate BMP2-associated inflammation and promote chondrogenesis to enhance BMP2-spinal fusion

Bone morphogenetic protein 2 (BMP2) is clinically applied for treating intractable fractures and promoting spinal fusion because of its osteogenic potency. However, adverse effects following the release of supraphysiological doses of BMP2 from collagen carriers are widely reported. Nanoclay gel (NC) is attracting attention as a biomaterial, given the potential for localized efficacy of administered agents. However, the efficacy and mechanism of action of NC/BMP2 remain unclear. This study explored the efficacy of NC as a BMP2 carrier in bone regeneration and the enhancement mechanism. Subfascial implantation of NC containing BMP2 elicited superior bone formation compared with collagen sponge (CS). Cartilage was uniformly formed inside the NC, whereas CS formed cartilage only on the perimeter. Additionally, CS induced a dose-dependent inflammatory response around the implantation site, whereas NC induced a minor response, and inflammatory cells were observed inside the NC. In a rat spinal fusion model, NC promoted high-quality bony fusion compared to CS. <i>In vitro,</i> NC enhanced chondrogenic and osteogenic differentiation of hBMSCs and ATDC5 cells while inhibiting osteoclastogenesis. Overall, NC/BMP2 facilitates spatially controlled, high-quality endochondral bone formation without BMP2-induced inflammation and promotes high-density new bone, functioning as a next-generation BMP2 carrier.