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.