In Situ Forming Hydrogels Based on Tyramine Conjugated 4-Arm-PPO-PEO via Enzymatic Oxidative Reaction

• Published in: Biomacromolecules 2010-03, Vol.11 (3), p.706-712
• Main Authors: Park, Kyung Min, Shin, Young Min, Joung, Yoon Ki, Shin, Heungsoo, Park, Ki Dong
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Applied sciences; Biological and medical sciences; Epoxy Compounds - chemistry; Exact sciences and technology; General pharmacology; Horseradish Peroxidase - chemistry; Hydrogels; Hydrogen Peroxide - chemistry; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Microscopy, Electron, Scanning; Organic polymers; Oxidation-Reduction; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polyethylene Glycols - chemistry; Properties and characterization; Rheology; Solution and gel properties; Spectroscopy, Fourier Transform Infrared; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Tyramine - chemistry
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm9012875

Over the past decades, hydrogels have been widely studied as biomaterials for various biomedical applications like implants, drugs and cell delivery carriers because of their high biocompatibility, high water contents and excellent permeability for nutrients and metabolites. Especially, in situ forming hydrogel systems have received much attention because of their easy application based on minimal invasive techniques. Chemical cross-linking systems fabricated using enzymatic reactions have various advantages, such as high biocompatibility and easy control of reaction rates under mild condition. In this study, we report enzyme-triggered injectable and biodegradable hydrogels composed of Tetronic-tyramine conjugates. The Tetronic-tyramine conjugates were synthesized by first reacting Tetronic with succinic anhydride and subsequent conjugation with tyramine using DCC/NHS as coupling reagents. The chemical structure of Tetronic-succinic anhydride-tyramine (Tet-SA-TA) copolymer was characterized by 1H NMR and FTIR. The hydrogels were prepared from a Tet-SA-TA solution above 3 wt % in the presence of horseradish peroxidase (HRP) and H2O2 under physiological conditions. Their mechanical property, gelation time, swelling ratio and degradation time were evaluated at different polymer, HRP, and H2O2 concentrations. In addition, a cyto-compatibility study was performed using the MC3T3-E1 cell line. In the cytotoxicity test, it was clear that the Tet-SA-TA hydrogel had no apparent cytotoxicity except for the hydrogel formed with 0.25 wt % H2O2 due to the cytotoxicity of residual H2O2. In conclusion, the obtained results demonstrated that the Tet-SA-TA hydrogel has great potential for use as an injectable scaffold for tissue engineering and as a drug carrier for controlled drug delivery systems.