Enzymatically Crosslinked Poly(γ -Glutamic Acid) Hydrogel with Enhanced Tissue Adhesive Property

Abstract

Enzymatic crosslinking of polymer-catechol conjugate in the presence of horseradish peroxidase (HRP) and H2O2 has emerged as an important method to fabricate in situ-forming, injectable hydrogels. Subsequently, tissue adhesion studies using catechol-containing polymers were extensively reported. However, due to the presence of numerous variables such as polymer concentration, oxidizing agent/enzyme, and stoichiometry, the design of polymer with optimized tissue adhesive property is still challenging. In this study, poly(γ-glutamic acid) (γ-PGA)-dopamine conjugate (PGADA) was synthesized, and in situ hydrogels were fabricated via enzymatic crosslinking of catechol moiety. To optimize the tissue adhesive property of the PGADA hydrogel, the effect of various factors, such as polymer concentration, catechol substitution degree (DS), HRP concentration and H2O2 content, on the gelation behavior and mechanical strength was investigated. The gelation behavior of PGADA hydrogels was characterized by a rheometer and rotational viscometer. Also, the possibility of its use as a tissue adhesive was examined by evaluating the tissue adhesion strength in vitro and in vivo.