Construction of hollow polydopamine nanoparticle based drug sustainable release system and its application in bone regeneration

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration.They,however,still face disadvantages of high toxicity,low biocompatibility,and low drug-load capacity.In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area,we evaluated the hollow polydopamine nanoparticles(HPDA NPs),in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect.Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility.Results of qRT-PCR,ALP,and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells(rBMSCs)in vitro.Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo,especially tacrolimus.These results suggest that the HPDA NPs,the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability,have good prospect to treat the bone defect in future clinical practice.

Brasenia-inspired hydrogel with sustained and sequential release of BMP and WNT activators for improved bone regeneration

Although bone morphogenetic protein(BMP) and WNT signaling play pivotal roles in bone development,homeostasis, and regeneration, the applications of proteins to stimulate corresponding signaling pathways showed limited outcomes in the repair and regeneration of bone defects that might be attributed to the reciprocal interventions of these pathways. In order to satisfy the combinational and sequential activation of BMP and WNT pathways, inspired by the heterogeneous hydrogel-liked structures of Brasenia, heterogeneous alginate/chitosan hydrogels were fabricated and spatially loaded with FK506 and BIO to achieve sustained and sequential release of the activators. Alkaline phosphatase staining, alizarin red staining and q RT-PCR results suggested that FK506 and BIO enhanced osteoblastic differentiation in vitro when used separately. Besides, by mixing and matching the activators and the hydrogel layers, a superior releasing mode that a combination of early FK506 release and following BIO release was identified via both in vitro and in vivo explorations for most efficient bone regeneration. These results suggested that drug-loaded heterogeneous hydrogels possess great potentials in treating bone loss defects for future clinical practice.