Controllable fabrication of hydroxybutyl chitosan/oxidized chondroitin sulfate hydrogels by 3D bioprinting technique for cartilage tissue engineering.

Biological regeneration of articular cartilage continues to be a challenge at present. Functional engineered implants with patient-specific sizes are difficult to achieve. The aim of this study is to fabricate a biocompatible cell-laden hydrogel with a designable structure. Covalent hydrogels were prepared with water soluble hydroxybutyl chitosan (HBC) and oxidized chondroitin sulfate (OCS) via a Schiff-base reaction. With the aid of three-dimensional (3D) bioprinted sacrificial molds, hydroxybutyl chitosan/oxidized chondroitin sulfate (HBC/OCS) hydrogel with various structures were obtained. After the material constituent optimization process, an injectable hydrogel with a uniform porous structure of 100 μm average pore size was developed to form macroporous hydrogel. In vitro and in vivo biocompatibility of optimized HBC/OCS hydrogel were also carefully assessed. The results indicated that human adipose-derived mesenchymal stem cells could be 3D cultured in HBC/OCS hydrogel maintaining good viability. Moreover, the hydrogels were found to trigger the least amount of pro-inflammatory gene expression of macrophage and to inhibit acute immune responses in 7 days. These results demonstrate the potential of HBC/OCS hydrogels as a cell delivery system for cartilage tissue engineering.