Abstract
Silk suture material is primarily composed of silk fibroin and regarded as a non-resorbable material. It is slowly degraded by proteolysis when it is implanted into the body. 4-Hexylresorcinol (4HR) is a well-known antiseptic. In this study, the biodegradability of 4HR-incorporated silk sutures were compared to that of untreated silk sutures and polyglactin 910 sutures, a commercially available resorbable suture. 4HR-incorporated silk sutures exhibited anti-microbial properties. Matrix metalloproteinase (MMP) can digest a wide spectrum of proteins. 4HR increased MMP-2, -3, and -9 expression in RAW264.7 cells. MMP-2, -3, and -9 were able to digest not only silk fibroin but also silk sutures. Consequently, 59.5% of the 4HR-incorporated silk suture material remained at 11 weeks after grafting, which was similar to that of polyglactin 910 degradation (56.4% remained). The residual amount of bare silk suture material at 11 weeks after grafting was 91.5%. The expression levels of MMP-2, -3 and -9 were high in the 4HR-incorporated silk suture-implanted site 12 weeks after implantation. In conclusion, 4HR-treated silk sutures exhibited anti-microbial properties and a similar level of bio-degradation to polyglactin 910 sutures and induced higher expression of MMP-2, -3, and -9 in macrophages.
Highlights
4-Hexylresorcinol (4HR) is a resorcinolic lipid and has been used as an antiseptic[9] and food ingredient for preventing melanosis10. 4HR is an amphiphilic molecule because of its 2 hydroxyl groups and long alkyl group[11]
4HR can interact with target proteins via both hydrophobic and hydrophilic interactions
matrix metalloproteinase (MMP) are enzymes that are responsible for proteolysis and are highly expressed in the acute inflammatory phase and late remodeling phase[20]
Summary
4-Hexylresorcinol (4HR) is a resorcinolic lipid and has been used as an antiseptic[9] and food ingredient for preventing melanosis10. 4HR is an amphiphilic molecule because of its 2 hydroxyl groups and long alkyl group[11]. Hydrophobic interactions can occur between the hydrophobic domain of the target protein and the long alkyl group of 4HR. In the case of hydrophilic interactions, preferential hydration can occur depending on the type of solvent[12] Using these 2 types of interactions, 4HR can be incorporated into proteins such as bone matrix. A group of matrix metalloproteinase (MMP) can degrade silk fibroin[19]. If 4HR can increase MMP expression in macrophages, 4HR-incorporated silk sutures can be degraded based on the schedule of macrophage activation during the wound healing process. The actual proteolysis of manufactured silk sutures by MMPs should be demonstrated. The biodegradation of 4HR-incorporated silk sutures should be demonstrated by in vivo experiments
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