Accelerating periodontal regeneration through injectable hydrogel-enabled sequential delivery of nanoceria and erythropoietin

Periodontitis is a chronic inflammatory disease characterized by persistent host immune overreaction, resulting in irregular alveolar shape after absorption, making local drug delivery a huge challenge. Herein, an injectable Fmoc-Phe3 hydrogel (FPH) with ceria nanoparticle (CNP) and erythropoietin (EPO) was prepared (EPO/CNP@FPH) for local drug delivery into the irregular periodontal pocket. The release of EPO and CNP was 61.33 % and 69.67 % respectively within the first 3 days and the release of CNP was faster than that of EPO during the process, which is the prerequisite for regeneration. The composite hydrogel enabled the switch in macrophage phenotype from M1 to M2 polarization by scavenging redundant ROS. It further increased the ability of angiogenesis and osteogensis. The EPO/CNP@FPH composite hydrogel exerted a remarkable therapeutic effects enabling irregular alveolar bone regeneration in rat model of periodontitis. Taken together, the hydrogel loaded with EPO and CNP showed a great potential for reducing inflammation and promoting periodontal regeneration in irregular regions, which may be a promising candidate for periodontitis treatment.