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Background  Without exploitation of possibly immunogenic and carcinogenic bone morphogenetic protein, we developed simple but clinically feasible artificial bone graft using osteoconductive hyaluronate (HA) hydrogels and bioactive MegaGen synthetic bone (MGSB).    Methods  HA hydrogels were synthesized by the crosslinking reaction between carboxyl groups of HA and amine groups of gelatin (GEL). Then, artificial bone grafts were prepared by mixing MGSB with HA-GEL hydrogels. The bone regeneration by the MGSB/HA-GEL hydrogel complex was assessed in the skull of New Zealand white male rabbits in 4 and 8 weeks.    Results  HA hydrogels were synthesized by the crosslinking reaction between carboxyl groups of HA and amine groups of gelatin (GEL). Then, artificial bone grafts were prepared by mixing MGSB with HA-GEL hydrogels.  In vitro  proliferation of preosteogenic cells was enhanced with increasing molecular weight of HA. In addition, histological analysis of dissected tissues with hematoxylin and eosin staining confirmed the effective  in vivo  bone regeneration by the MGSB/HA-GEL hydrogel complex. The MGSB/HA-GEL hydrogels were well resorbed and partially substituted to the lamellar bone after implantation for 8 weeks.    Conclusions  The novel artificial bone graft of MGSB/HA-GEL hydrogel complex for effective bone regeneration might be clinically feasible for further development.

Effect of osteoconductive hyaluronate hydrogels on calvarial bone regeneration