Enhancing osteochondral defect repair ability of hyaluronic acid/collagen hydrogel by icariin chemical conjugation

摘要

The articular cartilage lesions involving the cartilage and the subchondral bone is difficult to heal and will lead to severe pain and dysfunction. The different microenvironments of cartilage and subchondral bone present a higher requirement for the combined repair of it. Hydrogel can adapt to the lesion morphology flexibly, have injectable potential, and can meet the needs of minimally invasive operation. However, comparing with pre-constructed surgical implantable combined restorations with calcification zone, hydrogel is difficult to accurate design the unique properties for cartilage and subchondral bone defection area, and difficult to ensure the suitable seed cells cytobiological properties especially the differentiation direction of the seeded stem cells. Therefore, to design hydrogel scaffold which can induce the seeded cells to desired differentiation direction depending on local tissue microenvironments has its clear clinical significance. In this study, a flavonol glycoside named icariin which was considered to have the ability to promote both cartilage and bone formation was chemically conjugated to hyaluronic acid/collagen hydrogel, and mesenchymal stem cells were seeded into. Then, the chondrogenesis and bone formation ability of the hydrogel constructs were investigated in the cartilage and bone induction culture conditions respectively. The results show that the conjugated icariin can be released gradually. The morphology of the seeded cells in icariin conjugated hydrogel show chondrocytes-liked, more chondriod tissue is observed on the stained sections, the expression of cartilage related genes and the secretion of cartilage matrix in the hydrogel constructs are obviously up-regulated under cartilage inducing microenvironment. In bone inducing microenvironment, the seeded cells in the icariin conjugated hydrogel showed osteoblasts morphology, deposited calcium can be obviously observed, the expression of bone related genes and proteins are significantly increased. The results suggest that the chemical conjugation of flavonol glycosides on hydrogel scaffolds may help the scaffold to regulate the cytobiological properties of the seeded cells, and may prompt the application of the hydrogel in the repair for the defection of the complex tissue.