Preparation Of Chitosan/Modified Nano Hydroxyapatite Composite Hydrogel And Evaluation Of Its Effectiveness In Repairing Cartilage Defects

Cartilage repair remains a great clinical challenge for researchers and also for orthopedic surgeons. To date, many therapeutic methods have been developed to repair articular cartilage defects, but are still unable to obtain the desired results. Hydrogel materials has long been considered to be the more ideal material used for articular cartilage repairation due to its good biocompatibility, three-dimensional structure similar to that of ECM, proper pore structure, and good mechanical properties for cell adhesion and migration. And chitosan(CS)/nano-hydroxyapatite(HA) composite hydrogel has currently got wide applications in biomedical and tissue engineering resulting from its good bioactivity, absorbability and biodegradability. For further improvement of compatibility between CS and HA, chitosan-grafting modification was carried out on the HA surface to prepare hydroxyapatite-grafted-chitosan(HA-g-CS) in this study. The results of FT-IR, TGA and XRD indicated that CS was successfully grafted onto HA surface, SEM observation showed that the dispersity of HA-g-CS in the CS matrix was significantly improved, and the CS/HA-g-CS hydrogel exhibited much more better compression performance than the CS/HA. The biocompatibility evaluation of CS/HA-g-CS composite hydrogel showed that the cytotoxicity, systemic acute toxicity, systemic subacute toxicity, sensitivity and safety of implantation of the materials meet the national standard requirements, and this novel composite hydrogel was expected to be served as a tissue engineering material.Finally, the CS/HA-g-CS composite hydrogel was used for valuation of rat’s articular cartilage defect reparation. The gross observation and histological analysis were performed after 4 weeks and 12 weeks of transplantation respectively. The results showed that both CS/HA-g-CS and CS/HA composite hydrogel could promote the repairation of cartilage defect, and the CS/HA-g-CS composite hydrogel had better repair effect than that of CS/HA one. Articular cartilage defects filled with CS/HA-g-CS composite hydrogel could achieved ideal repair effect at weeks 12 after opration, and the thickness and color of the repaired tissue were consistent with the surrounding tissue. The expression levels of Col-II mRNA, mRNA BMP-2 and GAG mRNA were increased with the prolongation of the repair time. To sum up, the CS/HA-g-CS composite hydrogel has good capability to repair the articular cartilage defects, and further study will lay the foundation for the development and application of new type of articular cartilage repair products.