Thermosensitive hydrogels could function as scaffolds and delivery vehicle of natural flavonoids. The current study aimed to investigate effects of chitosan/collagen ratios on properties of thermosensitive beta‐glycerophosphate (bGP) chitosan/collagen hydrogels as delivery vehicle of quercetin and then examined effects of quercetin‐hydrogels on growth and cell viability of human periodontal ligament stem cells (hPDLSCs). Microstructure and physical, mechanical and antioxidant properties and quercetin release profiles of the hydrogels were investigated. Fourier transform infrared spectroscopy and X‐ray powder diffraction analyses were performed to examine gelation process of the hydrogels. Antioxidant assays were conducted to measure antioxidant capacity of quercetin‐hydrogels. It was found that bGP‐chitosan/collagen hydrogels exhibited porous structures with interconnected pore architecture and could sustain quercetin release. Chitosan content improved well defined porous structure, increased porosity of the hydrogels and decreased releasing rate of quercetin from the hydrogels. The quercetin‐bGP‐2:1 (wt/wt) chitosan/collagen hydrogels exhibited antioxidant capacity and were able to promote growth of hPDLSCs in a dose dependent manner. In conclusion, the thermosensitive quercetin‐bGP‐2:1 (wt/wt) chitosan/collagen hydrogel demonstrated optimal properties of scaffolds for bone tissue engineering and sustained release of natural flavonoids. Incorporating quercetin in the chitosan/collagen hydrogel enhanced bioactive microenvironment that supported stem cell encapsulation.
Thermosensitive chitosan/collagen hydrogels are osteoconductive and injectable materials. In this study, we aimed to improve these properties by adjusting the ratio of nanohydroxyapatite particles to calcium carbonate microcapsules in a β-glycerophosphate-crosslinked chitosan/collagen hydrogel. Two hydrogel systems with 2% and 5% nanohydroxyapatite particles were studied, each of which had varying microcapsule content (i.e., 0%, 1%, 2%, and 5%). Quercetin-incorporated calcium carbonate microcapsules were prepared. Calcium carbonate microcapsules and nanohydroxyapatite particles were then added to the hydrogel according to the composition of the studied system. The properties of the hydrogels, including cytotoxicity and biocompatibility, were investigated in mice. The calcium carbonate microcapsules were 2–6 µm in size, spherical, with rough and nanoporous surfaces, and thus exhibited a burst release of impregnated quercetin. The 5% nanohydroxyapatite system is a solid particulate gel that supports homogeneous distribution of microcapsules in the three-dimensional matrix of the hydrogels. Calcium carbonate microcapsules increased the mechanical and physical strength, viscoelasticity, and physical stability of the nanohydroxyapatite hydrogels while decreasing their porosity, swelling, and degradation rates. The calcium carbonate microcapsules–nanohydroxyapatite hydrogels were noncytotoxic and biocompatible. The properties of the hydrogel can be tailored by adjusting the ratio of calcium carbonate microcapsules to the nanohydroxyapatite particles. The 1% calcium carbonate microcapsules containing 5% nanohydroxyapatite particle–chitosan/collagen hydrogel exhibited mechanical and physical strength, permeability, and prolonged release profiles of quercetin, which were superior to those of the other studied systems and were optimal for promoting bone regeneration and delivering natural flavonoids.
Cuttlebone (CB) is a marine waste-derived biomaterial and a rich source of calcium carbonate for the biosynthesis of the calcium phosphate (CaP) particles. The current study aimed to synthesize CB derived biphasic calcium phosphate (CB-BCP) and investigate biological activity of the CB-CaP: hydroxyapatite (CB-HA), beta-tricalcium phosphate (CB-b-TCP) and biphasic 60:40 (w/w) HA/b-TCP (CB-BCP) with the human dental pulp stem cells (hDPSCs). The particles were synthesized using solid state reactions under mild condition and properties of the particles were compared with a commercial BCP as a reference material. Morphology, particle size, physicochemical properties, mineral contents, and the ion released patterns of the particles were examined. Then the particle/cell interaction, cell cytotoxicity and osteogenic property of the particles were investigated in the direct and indirect cell culture models. It was found that an average particles size of the CB-HA was 304.73
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