Evaluation of gelatin hydrogel crosslinked with various crosslinking agents as bioadhesives:In vitro study

Abstract

Bioadhesives are used for tissue adhesion and hemostasis in surgery. A gelatin-resorcinol mixture crosslinked with formaldehyde (GRF glue) and/or glutaraldehyde (GRG) is used for this purpose. Although the bonding strength of the GRF glue to tissue is satisfactory, concerns about the cytotoxicity of formaldehyde are reported in the literature. It was suggested that the cytotoxicity problem of the GRF glue may be overcome by changing its crosslinking method. The study was therefore undertaken to assess the feasibility of using an epoxy compound (GRE glue), a water-soluble carbodiimide (GAC glue), or genipin (GG glue) to crosslink with a gelatin hydrogel as new bioadhesives. GRF glue and GRG glue were used as controls. The results of our cytotoxicity study suggested that the cellular compatibility of the GAC and GG glues was superior to the GRF, GRG, and GRE glues. The gelation time for the GG glue was relatively longer than the GRF and GRG glues, while no gelation time could be determined for the GAC glue. Additionally, it took approximately 17 h for the GRE glue to become adhesive. The GRF and GRG glues had the greatest bonding strengths to tissue among all test adhesives, while the bonding strengths of the GAC and GG glues were comparable. In contrast, there was almost no bonding strength to tissue for the GRE glue. However, the GRF and GRG glues were less flexible than the GAC and GG glues. Subsequent to the bonding strength measurement, each test adhesive was found to adhere firmly to the tissue surface and underwent cohesive failure during the bond breaking. In conclusion, the GRF and GRG glues may be used as tissue adhesives when their ability to bind tissue rapidly and tightly is required; the GAC and GG glues are preferable when the adhesive action must be accompanied with minimal cytotoxicity and stiffness; and the GRE glue is not suitable for bioadhesion in clinical applications.

The use of collagen cross‐linking agents to enhance dentin bond strength

“…Despite its ability to induce cross-links in collagen, it is known for its cytotoxicity [18,19,20]. In the present study, the use of GD increased the bond strength for both adhesives when compared to control (Table 1).…”

Transdentinal cytotoxicity of glutaraldehyde on odontoblast-like cells

“…6,7 In medical research GA is used in many different ways such as the construction of bioprosthetic heart valves, 8,9 modification of gelatins and other materials and tissues. 8,10,11 In dental field, it has been used to desensitize sensitive exposed dentin, 12 to inhibit MMPs 13 and to increase the mechanical properties of demineralized collagen prior to bonding procedures.…”

Click‐Crosslinked Injectable Gelatin Hydrogels

“…Thermally stable, covalently crosslinked gelatin hydrogels have been formed most commonly using crosslinking strategies involving dialdehyde or carbodiimide chemistry and through free radical and enzymatic polymerizations. [7–11] However, most of these crosslinking methods directly target the amino acid side chains of gelatin polymers and may cross-react with cells and other proteins that also contain the same functional residues. This limits the ability of these strategies to be used for direct encapsulation of cells and proteins, and for in situ crosslinking after injection in vivo at target tissue sites.…”