Enzymatically Cross-Linked Poly(γ-glutamic acid) Hydrogel with Enhanced Tissue Adhesive Property

Abstract

Enzymatic cross-linking of polymer-catechol conjugates in the presence of horseradish peroxidase (HRP) and H₂O₂ has emerged as an important method to fabricate <i>in situ</i>-forming, injectable hydrogels. Subsequently, tissue adhesion studies using catechol-containing polymers were extensively reported. However, because of the presence of numerous variables such as polymer concentration, oxidizing agent/enzyme, and stoichiometry, the design of the polymer with optimized tissue adhesive property is still challenging. In this study, a poly(γ-glutamic acid) (γ-PGA)-dopamine (PGADA) conjugate was synthesized, and <i>in situ</i> hydrogels were fabricated <i>via</i> enzymatic cross-linking of a 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 using a rheometer and rotational viscometer. Also, the possibility of its use as a tissue adhesive was examined by evaluating the tissue adhesion strength <i>in vitro</i> and <i>ex vivo</i>.