Simultaneous delivery of BMP-2 factor and anti-osteoporotic drugs using hyaluronan-assembled nanocomposite for synergistic regulation on the behaviors of osteoblasts and osteoclasts <i>in vitro</i>

<div><p>To treat the osteoporosis and regulate the biological behaviors of both osteoblasts and osteoclasts, we prepared a natural polysaccharide-derived nanocomposite, containing alendronate-grafted hyaluronate (HA-Aln) and bone morphogenetic protein 2 (BMP-2) and investigated its synergistic regulation on the behaviors of osteoblasts and osteoclasts <i>in vitro</i>. The HA-Aln/BMP-2 nanocomposite was fabricated through the electrostatic interactions between the HA-Aln molecule and BMP-2 molecule. Here, BMP-2 was used to improve the osteoblast-mediated bone formation. Alendronate (Aln), a targeting ligand to bone matrix, was used to inhibit the osteoclast-mediated bone resorption. <i>In vitro</i> results showed that HA-Aln/BMP-2 nanocomposite could effectively maintain the bioactivity of loaded drugs. The osteoblasts that treated with the HA-Aln/BMP-2 nanocomposite presented a higher level of cell motility, alkaline phosphatase (ALP) activity, mineralization capacity, and osteoblast-related gene expressions (runt-related transcription factor 2, osterix, ALP, collagen type I, osteocalcin, and osteopontin), as compared to that of control group. Besides, the RAW264.7 cells that were treated with HA-Aln/BMP-2 nanocomposite showed a lower level of osteoclastic differentiation. Overall, the HA-Aln/BMP-2 nanocomposite exhibits promising potential as an efficient carrier for co-delivery of anti-osteoporotic drug and growth factors to promote osteoblastic differentiation and bone formation while suppressing osteoclastic activity.</p></div>