Preparation Of Self-healing Hydrogels And Application In Osteochondral Repair

Articular cartilage,with complex hierarchical structure,has limited ability to self-repair after injury,and currently,there’s still lack of effective clinical treatments.The cartilage tissue engineering with rapid development opens a new route for the treatment of cartilage defects.However,Cartilage defects will develop into osteochondral defects in the absence of effective treatments.Due to the dissimilar regenerative abilities and characteristics between cartilage and subchondral bone,therefore,the construction of an osteochondral integrated scaffold with firm interface is of great significance.In this paper we prepared a water-soluble chitosan derivative CEC and a hyaluronic acid derivative containing aldehyde groups.SNHC and SNHS hydrogel were prepared based on the Schiff-base reaction between CEC and OHA.It was found that we can regulate of the mechanical property of hydrogels by changing the solid content and composition.A bilayered single network osteohongdral scaffold(SNHO)with a firm interface was successfully fabricated based on the self-healing property of SNHC and SNHS hydrogels.SNHO hydrogel has good biocompatibility,but the existence of dynamic imine bonds and enzymes in complete medium accelerated the degradation of this hydrogel,and make it difficult to be used as an implant.In order to solve the fast degradation problem of self-healing hydrogels,we introduced PEGDA into the hydrogels,and combined the Schiff-base reaction and free radical reaction to prepare DNHC and DNHS double network self-healing hydrogels for cartilage and subchondral bone,respectively.These hydrogels,with good cytocompatibility,are not only suitable for cell survival,but also can promote cell proliferation,without significant differences to the control group.The results of the subcutaneous implant tests showed that acute inflammation appeared after 10 d post-implanting,and inflammation almost disappeared after 20 d post-implanting,which suggested that these hydrogels can quickly adapt to the environment in vivo.Rheological and DMA tests proved that double network structures won’t affect the self-healing property of hydrogels.A bilayered double network osteohongdral scaffold(DNHO)with a firm interface was fabricated based on the self-healing property of DNHC and DNHS hydrogels.The DNHO hydrogel can maintain its integrated bilayered structure after soaking in the complete medium for 30 d.Finally,we investigated the in vitro chondrogenic differentiation of BMSC cells in DNHC hydrogel.Furthermore,several scaffolds were used to repair the osteochondral defects in rabbits.We proved that scaffolds encapsulated BMSC cells have better repair effects.Meanwhile,the integrated osteochondral scaffolds are more likely to promote the regeneration of cartilage and subchondral bone than the pure cartilage scaffolds.