Sulfonated PEEK-statins delivery system enhances bone repair in mice with skull defect

Abstract

Objective To explore the effect of sulfonated poly-ether-ether-ketone (SPEEK)-statin delivery system on the repair of bone defect, H-type blood vessels and bone formation. Methods The mouse model of skull defect was established, SPEEK-pravastatin (SPEEK-Pra) and sulfonated SPEEK-simvastatin (SPEEK-Sim) delivery system were constructed, respectively. Then the samples with different concentration gradients (SPEEK 0.16 mg/mL, SPEEK -Pra 0.16 mg/mL, SPEEK -Sim 0.55 mg/mL, SPEEK -Sim 1.1 mg/mL, SPEEK -Sim 2.2 mg/mL) were implanted into the skull defect of mice, respectively. After 8 weeks, the skull samples were collected, and micro-CT scanning was used to observe the bone regeneration around of the defects, and CD31 and EMCN immunofluorescent staining was utilized to label H-type blood vessels. Results SPEEK can be used as a payload for statins. Micro-CT results showed that the thickness of skull were significantly larger in SPEEK-sim 1.1 mg/mL and SPEEK-sim 0.55 mg /mL groups than the other 3 groups, with that of the SPEEK group (without drug loading) lowest. Immunofluorescence assay found that the double-positive area was clearly visible in the SPEEK-sim 1.1 mg /mL group, but not observed in the SPEEK group and the SPEEK-pra 0.16 mg/mL group. Conclusion SPEEK-statin sustained-release system optimizes the osteogenic properties of SPEEK, which may be related to the protective effect of H blood vessel.

Keywords

• osteogenesis
• angiogenesis
• sulfonated peek
• simvastatin
• pravastatin