Injectable Hydrogel Containing Chitosan Oligosaccharide and MESPtide-Loaded Microspheres for Stepwise Repair of Inflammatory Bone Defects

Inflammatory bone defects are difficult to treat because of their complex morphology and the inefficiency of bone induction with current methods. Peptidomics of periodontal tissues from patients with inflammatory bone defects and controls identified a novel 19-residue peptide, MESPtide, which was formulated into microspheres within an injectable hydrogel containing chitosan oligosaccharide (i-P@COS). The hydrogel rapidly shed chitosan oligosaccharide, resulting in anti-inflammatory effects, and then gradually released the peptide, which produced both anti-inflammatory and osteogenic effects in cultures of MC3T3-E1 cells and in a rat model of inflammatory bone defects. These osteogenic effects involved the upregulation of bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2), as well as activation of signaling by Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3). This microsphere–hydrogel delivery system shows promise for the stepwise treatment of inflammatory bone defects.