The desirable properties of a matrix for tissue engineering applications appears to shift from a minimal model of supporting cell growth to a more inclusive role as a matrix to trigger the regeneration process. This requirement has propelled efforts towards bio-functionalization of matrices both by chemical and textural modification of most advanced materials, including silk. Amongst different biomaterials, silk fibroin (SF) has been extensively used for various tissue engineering applications, because of its low immunogenicity and good mechanical strength, although low biological activity and a poor biodegradability rate has remained its major limitation for use in regenerative medicine. In the present study, the physical as well as biological properties of SF have been improved by incorporation of honey, a natural healing agent. Honey-blended SF films (HSF) demonstrated increased mechanical strength together with enhanced wettability, swelling ability and degradability without hampering the original mechanical and biological properties of both honey and SF. In addition, parallel-aligned nanostructures were produced over native SF and HSF using soft lithography to form two-dimensional nano-patterned membranes. HSF films demonstrated enhanced surface roughness in flat membranes and even more so in nano-patterned membranes when compared with native SF membranes which are essential for cellular adhesion and proliferation. Furthermore, biocompatibility and cellular behavior such as adhesion, proliferation, spreading and interaction of 3T3 fibroblast cells were improved using HSF when compared with using native SF membranes. Thus, HSF membranes with enhanced bio-physical properties are a potential material for use in regenerative medicine and tissue engineering applications.
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