title: Improved synthesis of hyaluronic acid hydrogel and its effect on tissue augmentation.
abstract: HA-HMDA hydrogels were developed by direct amide bond formation between the carboxyl groups of hyaluronic acid (HA) and hexamethylenediamine (HMDA) with an optimized carboxyl group modification in the preliminary experiment. However, these HA-HMDA hydrogels transformed into an unstable liquid form after steam sterilization, and were problematic for application to actual dermal filler. A new method to overcome the problem of the previously developed HA-HMDA hydrogels is to prepare them by adjusting the pH in this study. Not only are these improved HA-HMDA hydrogels prepared with lower amounts of cross-linking and activation agents compared to the previously developed hydrogels, but they also maintain a stable form after steam sterilization. These improved HA-HMDA hydrogels showed higher viscoelasticity and longer lasting effects than the previous ones, despite the fact that the amount of the HMDA used as a cross-linking agent as well as 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and 1-hydroxybenzotriazole monohydrated (HOBt) used as activation agents were substantially reduced. According to an in vivo test using a wrinkled mouse model, the improved HA-HMDA hydrogels exhibited significantly improved tissue augmentation effects compared to a positive control of Restylane, which is widely used for the tissue augmentation throughout the world. Furthermore, histological analysis revealed excellent biocompatibility and safety of the improved synthesized HA-HMDA hydrogels.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Xiang Mei
authors.initials: XM
authors.lastname: Yan
authors.forename: Moo Seok
authors.initials: MS
authors.lastname: Seo
authors.forename: Eui Jin
authors.initials: EJ
authors.lastname: Hwang
authors.forename: Il Hwan
authors.initials: IH
authors.lastname: Cho
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
authors.forename: Uy Dong
authors.initials: UD
authors.lastname: Sohn
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D003959:Diamines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D012212:Rheology; D012867:Skin / Q000378:metabolism / Q000648:ultrastructure*; D015595:Skin Aging
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D003959:Diamines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; C007297:1,6-diaminohexane