A Novel Thiolated Chitosan-Silica Hybrid Hydrogel for Bone Tissue Engineering

Objectives: Hydrogels combining inorganic-organic materials aim to mimic the composite nature of real bone by combining the toughness of a polymer phase with the compressive strength of an inorganic phase. Chitosan is a natural co-polysaccharide polymer which is widely used in drug delivery and bone tissue engineering. In the present study, a novel hydrogel was generated based on thiolated chitosan (TC) and silica for potential use in bone regeneration
Methods: A novel hybrid hydrogel composed of TC and silica was prepared along with a low molecular weight chitosan (LMWC)/silica hydrogel for comparison. The functionalisation reaction of chitosan and silica was investigated using Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). Hydrogel rheology were assessed using frequency, amplitude and time-dependent sweeps. Hydrogel degradation was examined in phosphate buffer saline (PBS) or PBS containing 1.5 mg/mL lysozyme. Silicon released from hydrogels during the degradation process was measured using inductively coupled plasma atomic emission spectroscopy, and chitosan and glycerol release were measured using high-performance liquid chromatography. Viability of osteoblasts encapsulated in hydrogels was evaluated using the live/dead assay
Results: FTIR spectra of TC/silica hydrogel showed characteristic absorption bands which included: Amide II, Si-O and Si-O-Si. NMR demonstrated a reaction between the epoxide ring of silica and thiolated chitosan. Rheological testing showed a solid-like response of TC/silica hydrogel and the gel had an adequate gelling time (1627 s ± 98) for use in surgical procedures. After 24 hours, silicon release remained at a relatively slow rate (0.3 µg/mL ± 0.2) over 21 days. All hydrogels exhibited limited cytotoxicity as viability of osteoblasts remained at >70% over 168 hours culture.
Conclusions: The newly developed TC/silica hydrogel exhibited specific degradation and mechanical properties with no significant cytotoxicity. Thus, the hybrid hydrogels may have potential to be used for bone tissue engineering