Functionalized Hydroxyapatite and Curcumin Incorporated Stimuli‐Responsive Low‐Exothermic and Injectable Poly(methyl methacrylate) Bone Cement for the Treatment of Osteomyelitis

Abstract

AbstractWith the increasing of bone diseases, bone substitute biomaterials have been urgently needed and recognized as effective therapeutic strategies for bone regeneration. However, the improper mechanical properties, uncontrolled curing time, and exothermic heat limited their clinical applications. Herein, a facile prepared injectable bone cement consisting of poly(methyl methacrylate), hydroxyapatite, curcumin, oxidized sodium alginate, and polyethylenimine is constructed. By taking advantage of the acid‐ and H2O2‐responsive covalent bonds, the resultant bone cement not only possessed superior compressive strength (>70 MPa), bending strength (>50 MPa), suitable curing time (9–14 min), and low exothermic heat (<42 oC), but also can release the drugs under the trigger of osteomyelitis microenvironment. Both at the cellular level and rat osteomyelitis models, the prepared bone cement exhibited excellent biocompatibility (cell survival rate: >97%; hemolysis ratio: <1.8%), anti‐bacterial (the lowest bacterial survival rate: ≈1.7%), anti‐inflammatory (the expressions of iNOS, CD86, TNF‐α, IL‐1β, and IL‐6 are significantly inhibited) and the ability to promote bone regeneration (proliferation of osteoblasts and inhibition of osteoclasts). It is believed that this work will provide a bioactive organic/inorganic composite material for bone tissue engineering, the distinctive human‐friendly low exothermic heat, and advantages of prodrug technique incorporated multi‐function integration endow them potential clinical application prospects.