Disulfide-crosslinked chitosan hydrogel for cell viability and controlled protein release

• Published in: European journal of pharmaceutical sciences 2009-06, Vol.37 (3), p.198-206
• Main Authors: Wu, Z.M., Zhang, X.G., Zheng, C., Li, C.X., Zhang, S.M., Dong, R.N., Yu, D.M.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Acetylcysteine - chemistry; Animals; Biological and medical sciences; Biomaterial; Cell Adhesion - drug effects; Cell growth; Cell Survival - drug effects; Chitosan - chemistry; Chitosan hydrogel; Controlled protein release; Cross-Linking Reagents; Delayed-Action Preparations; Disulfide bond; Disulfides - chemistry; Drug Compounding; Electrophoresis, Polyacrylamide Gel; General pharmacology; Hydrogels; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Microscopy, Electron, Scanning; Molecular Weight; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Proteins - administration & dosage; Proteins - chemistry; Rheology; Serum Albumin, Bovine - chemistry; Sulfhydryl Compounds - chemistry; Thermogravimetry
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2009.01.010

Synthetic hydrogel mimics of the extracellular matrix (ECM) were prepared by cross-linking a thiol-modified chitosan (CS). CS was chemically modified using N-acetyl- l-cysteine (NAC). To minimize interference with biological function, the degree of substitution of thiol groups was kept below 50%. Solution of thiolated CS was prepared in pH 7.4 phosphate buffered saline (PBS) and crosslinked by disulfide bond formation in air. The gelation mainly depended on the content of thiol groups on thiolated CS, concentration of thiolated CS and the molecular weight of CS. Thermogravimetric analysis showed the thermal stabilities of CSS-S hydrogels. Results from SEM observation showed a porous 3D hydrogel structure with pores ranging from 5 to 30 μm. In vitro release showed that insulin and BSA release could be controlled by choosing the composition, loading and disulfide bond contents. In vitro cell compatibility of the hydrogels on NIH 3T3 cells was evaluated, indicating that the hydrogels were biocompatible and the cells could migrate into the hydrogels. Moreover, cells were viable and preserved 3D cell morphology inside the hydrogels. These results demonstrate that disulfide-crosslinked CS hydrogels, a new type of macroporous, biocompatible, synthetic polymers, are promising applications in tissue engineering, drug delivery, and cell culture.