Reduced Keratin-Based Bioadhesives for Peri-Implant Soft Tissue Sealing around Transcutaneous Metallic Prostheses

Abstract

When a percutaneous metallic implant breaches the skin barrier, the lack of peri-implant soft tissue sealing arising from a foreign body reaction and epithelial downgrowth results in delayed wound healing and closure. This facilitates microbial pathogen entry, leading to infection, inflammation, and ultimately, peri-implantitis. Toward this end, bioglue formulations of -human hair keratin (HHK) and chicken feather keratin coupled with polyphenols, dopamine (DOPA), quercetin (Q), and tannic acid (TA) were developed for peri-implant soft tissue sealing. A freeze-thaw gelation mediated by thiol recombination of reduced keratins was employed for attachment of soft tissue (porcine intestine) to titanium. Lap shear tests revealed that the adhesion strength of reduced keratins improved with polyphenol addition, with a maximal glue strength exhibited by HHK + TA (10:1 w/w) when applied between the porcine intestine and titanium. Rheological characterization ascertained shear-thinning behavior and injectability of the glues into wet aqueous media and dry surfaces. Despite inferior glue strength to commercial ethyl 2-cyanoacrylate bioglue, the keratin ± polyphenol glues were more skin compatible, evidenced by greater viability and proliferation of immortalized human skin epidermal keratinocytes (HaCaT) and equine dermal fibroblasts (E. Derm NBL6). Furthermore, the antioxidant activity of keratin ± polyphenol glue formulations conferred greater anti-inflammatory activity in bacterial lipopolysaccharide stimulated RAW 264.7 murine macrophages. Taken together, the application of keratin ± polyphenol glues for soft tissue sealing may be a promising approach to mitigate peri-implantitis around transcutaneous metallic prostheses.