LAUSR

Chitosan nanofibrous membranes have immense potential in tissue engineering and drug delivery applications because of their high degree of biocompatibility, their ability to mimic the extracellular matrix and increased surface area. However, their use is often limited due to their extreme hydrophilic nature causing them to lose their nanofibrous structure. In this study, chitosan membranes were modified either by acylation reactions using fatty acids of different chain lengths or tert-butyloxycarbonyl(tBOC) protecting groups to increase the hydrophobicity of the membranes and protect the nanofibrous structure. The modified membranes were characterized using scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, water contact angle and elemental analysis to confirm the addition of the modification groups. These membranes were then evaluated to control the release of a hydrophobic osteogenic drug-simvastatin (SMV). The interaction between SMV and the polymer were determined using molecular modeling. SMV and SMV loaded membranes were further tested for their in vitro cytotoxicity and osteogenic potential. Results showed that as the fatty acid chain length increased from two to six methylene groups, the hydrophobicity of the membranes increased (59.2±8.2° to 94.3±8.5°water contact angle). The amount of drug released from the membranes could be controlled by changing the amount of initial drug loading and the type of modifications. For a 500µg loading, after 4 weeks, the short chain fatty acid modified membranes released 17.8 ± 3.2% of the drug whereas a long chain fatty acid released only 4.8±0.8%. On the other hand, for a 50µg loading, short chain modified membranes released 73.3 ±33.3% of the loaded drug and the long chain membranes released 43±3.5%. The long chain fatty acid membranes released SMV for extended time periods of up to 90 days. This data was further supported by molecular modeling, which showed that SMV was more compatible with more hydrophobic membranes. Cell studies showed that SMV from 75 to 600ng/ml range possessed osteogenic potential in a dose dependent manner and the amount of SMV released from the most hydrophobic FA treated membranes was not cytotoxic and supported osteogenic differentiation. This study demonstrates our ability to control the release of a hydrophobic drug from chitosan membranes based on the clinical need.