[Chondrogenic and ameliorated inflammatory effects of chitosan-based biomimetic scaffold loaded with icariin].

Icariin (ICA) is a small molecule drug capable of promoting cartilage repair and ameliorating inflammation. Loading ICA into a biomaterial scaffold for cartilage tissue engineering will thus potentially enhance the biological functionality of the engineered scaffold. In this study, short fibers processed from electrospun poly(l-lactide--caprolactone) (PLCL) fibers which were prior coated with polydopamine (PDA), were mixed with citric acid doped chitosan solution (CC) for preparing short fibers reinforced chitosan hydrogel (PDA@PLCL/CC) by a freeze-thawing combined freeze-drying method. Thereafter, ICA was loaded into the PDA@PLCL/CC scaffold through physical adsorption to generate a newly engineered biomimetic cartilage scaffold (ICA-PDA@PLCL/CC). Finally, ICA-mediated chondrogenic and ameliorated inflammatory effects of the ICA-PDA@PLCL/CC scaffold were examined using rabbit chondrocytes. The results showed that the ICA-free PDA@PLCL/CC scaffold possessed appropriate pore size and porosity (> 80%), high water absorbance capacity and improved mechanical performance, and also promoted chondrocyte proliferation and adhesion. The ICA-laden ICA-PDA@PLCL/CC scaffold was evidenced to maintain cytomorphology, upregulate the expression of chondrogenic gene (), glycosaminoglycan gene (), and type Ⅱ collagen gene () as well as the synthesis of the cartilage matrix. In the presence of a simulated inflammation, the ICA-PDA@PLCL/CC scaffold was found to reduce chondrocyte fibrosis, effectively downregulate the expression of proinflammatory factors interleukin-6 (), interleukin-1 (), and inducible nitric oxide synthase () in chondrocytes. It can also reduce matrix metalloproteinase-3 () expression and promote the synthesis of the extracellular matrix glycosaminoglycan (GAG) and type II collagen (Col II). The newly developed ICA-PDA@PLCL/CC scaffold may find applications in the regeneration and repair of cartilage defects.