Experimental Study On The Repair Of Rat Mandible Defect With Pearl Like Graphene Oxide Collagen Scaffold

Purpose:Tissue engineering based on bone repair are of great value for the treatment of mandibular defect.Our previous study found that by soaking the graphene oxide functionalized collagen(Col-GO)microtissue in simulated body fluid(SBF),a bone-like hydroxyapatite coating can be formed on the surface to improve its osteoinductivity as well as bone repair effect.However,the insufficient depth of mineralization makes the osteogenesis suboptimal.In order to improve,We plan to use microarraychip to construct the Pearl like graphene oxide collagen scaffold to improve the mineralization depth,at the same time,in order to detect the symptoms of mandible defects in rats,the Pearl like graphene oxide collagen scaffold was used to evaluate whether it has repair effect.Methods:To construct the single layered micro-tissue,the 800 μm diameter Col-GO micro-tissue was fabricated and then immersed in SBF to simulate bio-mineralizationprocess as previously described.For the double layered micro-tissue,the pre-fabricated single-layered micro-tissue was immersed in 1200 μm diameter mold with Col-GO solution and was sequentially subject to gelation,lyophilization and SBF mineralization.Similarly,the 1500 μm diameter triple layered micro-tissue could be fabricated.At last,the micro-tissues with zero-layer,single-layer or triple-layer mineralization was independently assembled in 3D-printed PLA stents and analyzed in an animal experiment with rat mandibular bone defect model.Results:Using the novel pearl like graphene oxide collagen scaffold scheme proposed in this paper,SD rats were experimented and waited for 3 months,then the main body of the experiment was detected and analyzed by m CT,we found that the triple-layer mineralized Col-GO micro tissue generated significantly more new bone compared to single-layer mineralization,zero-layer mineralization as well as empty control groups.Moreover,though the four groups shared similar bone mineral density(BMD),the proportion of new bone(BV/TV)in the triple-layer mineralization group was twice the value of other groups.HE staining,Masson staining as well as OCN immunohistochemical staining further showed that the new bone in the triple-layer mineralization group was more mature compared to other groups,which was indicated by more internal bone lacuna as well as more OCN-positive cells.Conclusions:These data clearly show that compared with the large-scale scaffolds,the novel pearl like graphene oxide collagen scaffolds proposed in this paper can improve the mineralization depth,because the internal structure of the micro scaffolds can achieve the uniform mineralization effect,its mechanical properties are also significantly improved,and can significantly promote the repair of rat mandibular defects.