Development of A Novel Glue Consisting of Naturally-Derived Biomolecules: Citric Acid and Human Serum Albumin

Abstract

A novel glue consisting of human serum albumin (HSA) and citric acid derivative (CAD) was developed where the glue is named as CAD-A glue. In this adhesive, CAD works as a crosslinking reagent of HSA. For preparing crosslinking reagent CAD, using citric acid as a starting material, three carboxyl groups of a citric acid were modified with N-hydroxysuccinimide in the presence of 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride. From 1H-NMR spectrum, CAD with three active ester groups in a molecule was successfully synthesized with a high yield (more than 80%). The boding time of CAD-A glue to collagen-based casing was saturated within 15 minutes. The bonding strength of this glue to collagen-based casings increased with increasing of HSA concentration. The maximum bonding strength of CAD-A glue was a slightly low level compared to the bonding strength of cyanoacrylate adhesive and was 9 times higher than that of fibrin glue. The CAD-A glue showed excellent biocompatibility and high ability of wound closure similar to that of cyanoacrylate-based adhesive when glues were applied to the mouse skin. These results suggested that this developed adhesive had both tissue compatibility and bonding strength for use in clinical field.

Enhanced Neovascular Formation in a Novel Hydrogel Matrix Consisting of Citric Acid and Collagen

“…The combination of bFGF significantly increased vessel density and length in TSC [3]-AlCol [15], TSC [6]AlCol [7.5, 10] and TSC [10]-AlCol [7.5], as compared with those in untreated gels (Fig. 3A and 3B).…”

“…12) In the present study, we created a chemical gel matrix for the same purpose. This hydrogel matrix was formed by chemically cross-linking AlCol with TSC, [13][14][15] and can be combined with a potent angiogenic growth factor, basic fibroblast growth factor (bFGF). Application of this biomaterial in regenerative tissue is expected to lead to development of a vascular network in the regenerative tissue after implantation in vivo.…”

Poly‐(L‐lactic acid) and citric acid‐crosslinked gelatin composite matrices as a drug‐eluting stent coating material with endothelialization, antithrombogenic, and drug release properties

“…In addition, gelatin chains contain motifs such as arginine–glycine–aspartic acid (RGD) sequences that modulate cell adhesion, thereby exhibiting improved biological behavior compared with polymers that lack these cell recognition sites 22. We recently reported citric acid‐crosslinked gelatin matrices [AlGelatin‐trisuccinimidyl citrate (TSC)] composed of alkali‐treated gelatin (AlGelatin) and TSC as the crosslinker 23–26. AlGelatin‐TSC was demonstrated to exhibit antithrombogenic and endothelialization properties 27.…”

Tamibarotene-loaded citric acid-crosslinked alkali-treated collagen matrix as a coating material for a drug-eluting stent

“…Therefore, it is necessary to develop a novel biodegradable matrix with an antithrombogenic property that can promote endothelial cell adhesion after drug elution [7][8][9][10][11]. Recently, we have developed novel crosslinkers, organic acids with active ester groups, for use in biocompatible medical devices [12,13]. These crosslinkers, made of citric acid, maleic acid and tartaric acids, were reported to form biopolymer matrices as a result of the reaction between amino groups of the biopolymer and active ester groups of crosslinkers [14][15][16].…”