Injectable thermogelling chitosan for the local delivery of bone morphogenetic protein
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The aim of the present study was to evaluate the in vivo biocompatibility of injectable thermo gelling chitosan–ammonium hydrogen phosphate solution (chitosan–AHP) and its efficacy to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in a bioactive form. The thermogel showed a typical foreign body response upon subcutaneous implantation surrounded by a fibrous capsule. Even at 4 and 8 weeks post implantation, significant neutrophil infiltration was observed within the gel. Chitosan–AHP gel retained most of the loaded rhBMP-2 after a small initial release. The bioactivity of the released protein was demonstrated in vitro by the increase in alkaline phosphatase activity of mouse pre osteoblast cells (MC3T3-E1). Histological and micro-computed tomography (μCT) evaluation showed evidence of ectopic bone formation upon 4 μg/mL rhBMP-2 loaded chitosan–AHP injection. The study demonstrated a neutrophil mediated local tissue response to chitosan–AHP gel and its ability to encapsulate and maintain the bioactivity of rhBMP-2.
KeywordsChitosan Fibrous Capsule Ectopic Bone Formation Ammonium Hydrogen Phosphate Local Tissue Response
The authors greatly acknowledge the funding from USAMRMI -W81XWH-10-1-0653.
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