Multi-Crosslinked Strong and Elastic Bioglass/Chitosan-Cysteine Hydrogels with Controlled Quercetin Delivery for Bone Tissue Engineering

Chitosan-cysteine (CH-CY) conjugate with an optimal content of thiol groups was synthesized and combined with amino-functionalized mesoporous bioglass (ABG) nanoparticles (NPs) with radially-porous architecture to build multi-crosslinked ABG/CH-CY composite hydrogels. Besides the network formed by self-crosslinking of thiol groups in CY-derived side chains, difunctionalized PEG (DF-P) crosslinkers with varying lengths of PEG segments were used to crosslink amino groups on CH-CY or ABG NPs to form other networks in the composite gels. Quercetin (Que) was loaded into ABG NPs before these NPs were incorporated into the hydrogel, intending to achieve sustainable and controllable Que release from so-built ABG/CH-CY gels. The lengths of PEG segments in DF-P were found to impose remarkable impacts on the strength or elasticity of multi-crosslinked ABG/CH-CY hydrogels. Some ABG/CH-CY hydrogels had their elastic modulus of around 8.2 kPa or higher along with yielding strains higher than 70%, specifying their mechanically strong and elastic characteristics. In addition, these gels showed the ability to release Que and Si or Ca ions in controllable ways for various durations. The optimally achieved ABG/CH-CY hydrogels were injectable and also able to support the growth of seeded MC3T3-E1 cells as well as the specific matrix deposition. The obtained results suggest that these ABG/CH-CY gels have promising potential for bone repair and regeneration.Keywords:multi-crosslinked hydrogel;chitosan-cysteine conjugate;amino-functionalized bioglass nanoparticles;quercetin;strength and elasticity;controllable and sustainable release