Strontium-Doped\nWhitlockite\nScaffolds for Enhanced\nBone Regeneration

Bone\ngraft substitutes to repair critical-sized bone\nfractures\nhave experienced significant development over the last few decades.\nAmong them, whitlockite (WH)-based bone grafts have proven to be effective\nin mediating bone healing. In the current study, a next generation,\nnature-inspired scaffold was developed with strontium-functionalized\nwhitlockite nanoparticles (nSrWH) to enhance the intrinsic properties\nof WH. A series of nSrWH (with 2.5, 5, 7.5% Sr atomic substitution)\nwere fabricated using a rapid-mixing wet precipitation route. Subsequently,\nthe functionalized whitlockite was integrated into a gelatin-chondroitin\nsulfate scaffold and subjected to both <i>in vitro</i> and <i>in vivo</i> studies to investigate its osteogenic potential.\nResults indicated that nSrWH-containing scaffolds promoted osteogenic\ndifferentiation while inhibiting osteoclast activity. The positive\nimpact of nSrWH was found to be dose-dependent, with the 7.5% Sr atomic\nsubstitution exhibiting the most significant results. Furthermore,\nthe scaffold induced superior <i>de novo</i> bone regeneration\ncompared to its undoped counterpart in the mouse calvarial critical-sized\ndefect model. Collectively, these findings suggest that nSrWH nanoparticles\ninherit the beneficial properties of whitlockite, coupled by the therapeutic\neffects of Sr<sup>2+</sup>, operating in concert for an overall enhanced\nbone regeneration. As such, they constitute promising candidates to\nmeet the biomedical requirements for bioactive bone graft substitutes.