Mussel-inspired poly(γ-gl utamic acid)/nanosilicate composite hydrogels with enhanced mechanical properties, tissue adhesive properties, and skin tissue regeneration

Abstract

It was demonstrated herein that the adhesive property of catechol-functionalized nanocomposite hydrogel can be enhanced by tuning the cohesive strength due to the secondary crosslinking between catechol and synthetic bioactive nanosilicate, viz. Laponite (LP). The nanocomposite hydrogel consists of the natural anionic poly(γ-glutamic acid) (γ-PGA), which was functionalized with catechol moiety, and incorporated with disk-structured LP. The dual-crosslinked hydrogel was fabricated by enzymatic chemical crosslinking of catechol in the presence of horseradish peroxidase (HRP) and H₂O₂, and physical crosslinking between γ-PGA-catechol conjugate and LP. The PGADA/LP nanocomposite hydrogels with catechol moieties showed strong adhesiveness to various tissue layers and demonstrated an excellent hemostatic properties. These PGADA/LP nanocomposite hydrogels are potentially applied for injectable tissue engineering hydrogels, tissue adhesives, and hemostatic materials. STATEMENT OF SIGNIFICANCE: Recently, many attempts have been performed to manufacture high-performance tissue adhesives using synthetic and natural polymer-based materials. In order to apply in various biological substrates, commercially available tissue adhesives should have an improved adhesive property in wet conditions. Here, we designed a mussel-inspired dual crosslinked tissue adhesive that meets most of conditions as an ideal tissue adhesive. The designed tissue adhesive is composed of poly(γ-glutamic acid)-dopamine conjugate (PGADA)-gluing macromer, horseradish peroxidase (HRP)/hydrogen peroxide (H₂O₂)-enzymatic crosslinker, and Laponite (LP)-additional physical crosslinking nanomaterial. The PGADA hydrogel has tunable physicochemical properties by controlling the LP concentration. Furthermore, this dual crosslinked hydrogel shows strong tissue adhesive property, regardless of the tissue types. Specially the PGADA hydrogel has tissue adhesive strength four times higher than commercial bioadhesive. This dual crosslinked PGADA hydrogel with improved tissue adhesion property is a promising biological tissue adhesive for various tissue type in surgical operation.

Keywords: Dopamine; Dual crosslinking; Injectable hydrogel; Laponite; Poly(γ-glutamic acid); Tissue adhesives.