Ultraviolet Crosslinkable and Injectable Chitosan/Hydroxyapatite Hybrid Hydrogel for Critical Size Calvarial Defect Repair In Vivo

Abstract

To promote bone regeneration in vivo using criticalsize calvarial defect model, hybrid hydrogel was prepared by mixing chitosan with hydroxyapatite (HA) and ultraviolet (UV) irradiation in situ. The hydrosoluble, UVcrosslinkable and injectable Nmethacryloyl chitosan (NMAC) was synthesized via singlestep Nacylation reaction. The chemical structure was confirmed by 1HNMR and FTIR spectroscopy. NMAC hydrogel presented a microporous structure with pore sizes ranging from 10 to 60 خ¼m. Approximately 80% cell viability of NMAC hydrogel against encapsulated 3T3 cell indicated that NMAC is an emerging candidate for mimicking native extracellular matrix (ECM). NMAC hydrogel hybridized with HA was used to accelerate regeneration of calvarial bone using rabbit model. The effects of hybrid hydrogels to promote bone regeneration were evaluated using critical size calvarial bone defect model. The healing effects of injectable hydrogels with/without HA for bone regeneration were investigated by analyzing Xray image after 4 or 6 weeks. The results showed that the regenerated new bone for NMAC 100 was significantly greater than NMAC without HA and untreated controls. The higher HA content in NMAC/HA hybrid hydrogel benefited the acceleration of bone regeneration. About 50% closure of defect site after 6 weeks postimplantation demonstrated potent osteoinductivity of NMAC 100 UVcrosslinkable and injectable NMAC/HA hybrid hydrogel would allow serving as a promising biomaterial for bone regeneration using the criticalsize calvarial defect.