Injectable macro-porous chitosan/polyethylene glycol-silicotungstic acid double-network hydrogels based on “smashed gels recombination” strategy for cartilage tissue engineering

The lack of interconnected macro-porous structure of most injectable hydrogels lead to poor cell and tissue infiltration. Herein, we present the fabrication of injectable macro-porous hydrogels based on "smashed gels recombination" strategy. Chitosan/polyethylene glycol-silicotungstic acid (CS/PEG-SiW) double-network hydrogels were prepared via dual dynamic interactions. The bulk CS/PEG-SiW hydrogels were then smashed into micro-hydrogels with average sizes ranging from 47.6 to 63.8 μm by mechanical fragmentation. The CS/PEG-SiW micro-hydrogels could be continuously injected and rapidly recombined into a stable porous hydrogel based on the dual dynamic interactions between micro-hydrogels. The average pore size of the recombined porous CS/PEG-SiW hydrogels ranged from 52 to 184 μm. The storage modulus, compress modulus and maximum compressive strain of the recombined porous CS/PEG-SiW1.0 hydrogels reached about 47.2 %, 28.2 % and 127.6 % of the values for their corresponding bulk hydrogels, respectively. The recombined porous hydrogels were cytocompatible and could effectively support proliferation and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In a rat cartilage defect model, recombined porous CS/PEG-SiW hydrogels could promote cartilage regeneration. Hematoxylin and eosin (H&E), Safranin-O/Fast green and immunohistochemical staining confirmed the accumulation of glycosaminoglycans (GAG) and type II collagen (Col II) in regenerated cartilage.