Chemical characterization and biological properties of titania/hydroxyapatite-promoted biomimetic alginate-chitosan-gelatin composite hydrogels

Abstract

Ceramic nanoparticles, hydroxyapatite (HAP) and titania (TiO2) nanoparticles were commonly used as the reinforcing agent for biological materials due to their high chemical stability, low toxicity, outstanding biocompatibility and good bioactivity, which will be beneficial to enhance the physical, chemical and biological properties of composite hydrogels. To fundamentally improve the bio-applicability of alginate hydrogels, we attempted to fabricate titania/hydroxyapatite-promoted biomimetic alginate-chitosan-gelatin (Alg/TiO2/HAP-CS-GT) composite hydrogels by physical blending method using HAP nanoparticles as both the reinforcing agent and the endogenous cross-linking agent, followed by surface modification through alternately electrostatic assembly of chitosan (CS) and gelatin (GT). Meanwhile, the effects of the addition of TiO2 nanoparticles on the pore structure, mechanical properties, swelling, biodegradability, biological mineralization ability and biological activity of Alg/TiO2/HAP-CS-GT composite hydrogels were mainly studied. Experimental results showed that the resultant Alg/TiO2/HAP-CS-GT composite hydrogels exhibited good 3D morphology with the porosity in the range of 86.90%–77.62% and pore size ranging from 210 μm to 90 μm. Moreover, the compressive strength and modulus of Alg/TiO2/HAP-CS-GT composite hydrogels were significantly improved with increasing of TiO2 nanoparticles content and reached up to 0.329 ± 0.012 MPa and 0.558 ± 0.035 MPa, respectively. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and thermogravimetric analyses (TGA) implied that the interfacial interaction between TiO2 nanoparticles and polymer in Alg/TiO2/HAP-CS-GT composite hydrogels was inferred to be the hydrogen bond interaction. Furthermore, the addition of TiO2 nanoparticles could effectively regulate the swelling, in vitro biodegradation and biomineralization, and biological activity of the composite hydrogels. In particular, Alg/TiO2/HAP-CS-GT composite hydrogels could exhibit good cell adhesion and cell proliferation activity. When the addition amount of TiO2 nanoparticles was 1.0% (w/v), Alg/TiO2/HAP-CS-GT composite hydrogels exhibited the highest cell proliferation activity. In addition, with increasing of TiO2 content, the relative alkaline phosphatase (ALP) activity of cells on the Alg/TiO2/HAP-CS-GT composite hydrogels gradually increased, indicating that the addition of TiO2 nanoparticles could also effectively promote cell differentiation. On account of these excellent physical, chemical and biological activities of Alg/TiO2/HAP-CS-GT composite hydrogels, they were expected to be applied in the field of tissue engineering.