Hyaluronic acid – calcium phosphate nanocomposite hydrogel via in-situ precipitation process

Abstract

Hyaluronic acid (HAc) exhibits excellent biocompatibility and hydrophilicity, whereas it has limitations on biomedical applications due to poor biomechanical properties as well as fast in vivo degradation through enzymatic degradation. In this study, we have introduced in-situ precipitation method for fabrication of HAc-calcium phosphate (CaP) nanocomposite hydrogel in order to improve mechanical and biological behaviors of HAc under physiological conditions precipitating calcium phosphate nanoparticles. In particular, in-situ precipitation facilitates homogeneous and fast incorporation of nanoparticles into a polymer matrix. The nanocomposite hydrogels with various CaP content were fabricated and then evaluated to find optimal conditions of the hydrogels. The CaP nanoparticles were distributed homogeneously within HAc matrix, increasing surface roughness of the hydrogels, and appeared uniform with the size of ~200 nm. The degradation of the composite hydrogels was significantly retarded as compared to that of pure HAc hydrogels in hyaluronidase solution, showing improved chemical stability of the composite. Moreover, composite hydrogels exhibit improvement on rheological behaviors, indicating the shear moduli of composite hydrogels are 2.5-4 times as great as pure HAc hydrogel depending on the CaP content. Furthermore, fibroblast cells on the nanocomposite hydrogels showed more advanced progress of cell adhesion as compared to HAc hydrogel. The level of cell proliferation behaviors on nanocomposite hydrogels after 5 d was around 8 times higher than that on HAc hydrogel, implying the enhanced biocompatibility of composite hydrogels. By controlling the CaP amounts, mechanical and biological behaviors of the nanocomposite hydrogel can be optimized, exhibiting great potential for various biomedical applications.