Simvastatin loaded chitosan guided bone regeneration membranes stimulate bone healing.

Abstract

Electrospun chitosan membranes (ESCM) modified with short-chain fatty acids have the ability to control the release of simvastatin (SMV), an anti-cholesterol drug with osteogenic potential, for guided bone regeneration (GBR) applications. This study evaluated in vivo osteogenic effects of rapid short release of SMV (4weeks) vs long sustained release (8weeks) from acetic anhydride (AA)-and hexanoic anhydride (HA)-modified ESCMs, respectively. AA ESCMs loaded with 10 or 50µg SMV and HA ESCMs loaded with 50µg SMV were evaluated for biocompatibility and bone formation at 4 and 8weeks, in 5mm critical size rat calvarial defects, using histological evaluation and micro-CT analysis. No severe inflammatory response was noticed around the ESCMs. Less hydrophobic AA membranes showed signs of resorption by week 4 and were almost completely resorbed by week 8 whereas the more hydrophobic HA membranes resorbed slowly, remaining intact over 8weeks. In micro-CT analysis, 10µg SMV-loaded AA membranes did not show significant bone formation as compared to non-loaded AA membranes at either evaluation time points. 50µg SMV-loaded AA membranes stimulated significantly more bone formation than non-loaded AA membranes by week 4 (%bone=31.0±5.9% (AA50) vs 18.5±13.7% (AA0)) but showed no difference at week 8. HA membranes with 50µg SMV showed significantly more bone formation as compared to corresponding non-loaded membranes by week 8 (%bone=61.7±8.9% (HA50) vs 33.9±29.7% (HA0)), though such an effect was not significant at week 4. These results indicate that modified ESCMs may be used to control the release of SMV and promote bone healing in GBR applications.