Preparation and characterization of sponge-like composites by cross-linking hyaluronic acid and carboxymethylcellulose sodium with adipic dihydrazide

The objective of this study was to develop a novel kind of hyaluronic acid-based biomaterials which had the great potentials to be used as dermal fillers or applied in tissue augmentation or filling. A series of sponge-like composites were prepared by cross-linking different amounts of hyaluronic acid (HA) and carboxymethylcellulose sodium (CMC-Na). Adipic dihydrazide (ADH) was employed as the cross-linker and water-soluble 1-ethyl-3-[3-(dimethylaminopropyl)] carbodiimide (EDC) as the carboxyl-activating agent. Fourier-Transform Infrared (FT-IR) analysis was performed to characterize the expected amide linkages in the cross-linked composites, and the scanning electron microscopic (SEM) analysis was carried out to view the microstructures of the composites. Furthermore, the physico-chemical properties, such as swelling property, thermostability, the resistance to hyaluronidase (HAse) degradation and the antioxidant abilities against hydroxyl free radical ((OH)-O-center dot), were characterized. The presence of the amide peak at 1476.11 cm(-1) in FT-IR spectra indicated the cross-linking between HA and CMC-Na by ADH. As demonstrated by scanning electron microscopy (SEM), the microstructures of the composites were dependent on HA content. The equilibrium swelling ratio was 20.091 +/- 0.070, indicating the excellent water-uptake abilities of the composites. The HA-CMCNa composites showed a thermal stability up to 237 degrees C, independent of the composition of the prepared biomaterials. When exposed to phosphate-buffered saline (PBS) solution containing HAse (100 U/ml), all of the composites could be degraded quickly in 15 h. But when the concentrations of ADH and EDC in the cross-linking reaction system were increased up to 10 mmol/L, respectively, the degradation process lasted for 60 h. The prepared composites possessed great antioxidant abilities against (OH)-O-center dot and the ability to scavenge (OH)-O-center dot depended on the composition. With the high water-keeping ability and improved physico-chemical stabilities, the prepared biocompatible HA-CMCNa composites could be used as ideal alternatives for dermal fillers, tissue augmentation/filling biomaterials. (c) 2007 Published by Elsevier Ltd.