Biomedical application of silk requires the removal of sericin that is the gumming
material of native silk fibers. This is because sericin can elicit an adverse immune response
after implantation in the human body. However, the removal of sericin causes the silk fiber to
fray and weakens its structural property, making it very difficult to knit or braid them into a
scaffold for ligament tissue engineering applications. The aim of this study was to replace
sericinwith gelatin usingNDGAas a cross-linking agent to biomimic the natural structure of native
silk fibers. The physical properties and biocompatibility of the modified and native silk fibers were
compared by in vitro and in vivomodels.Themechanical and swelling properties of sericin-free silk
fibers were greatly increased after modification with gelatin. Both modified and native silk fibers
were shown to be nontoxic by in vitro cytotoxicity tests. The in vivo study demonstrated that the
modified silk fibers, after 4 weeks’ subcutaneous implantation in rats, caused little or no
inflammatory reaction as compared with native silk fibers. The superior mechanical properties
and lower inflammatory potential of modified silk fibers make them a promising candidate for
ligament tissue engineering applications