Coaxially Fabricated Dual-Drug Loading Electrospinning Fibrous Mat with Programmed Releasing Behavior to Boost Vascularized Bone Regeneration.

In clinical treatment, the bone regeneration of critical-size defects is desiderated to be solved, and the regeneration of large bone segment defects depends on early vascularization. Therefore, overcoming insufficient vascularization in artificial bone grafts may be a promising strategy for critical-size bone regeneration. Herein, a novel dual-drug programmed releasing electrospinning fibrous mat (EFM) with a deferoxamine (DFO)-loaded shell layer and a dexamethasone (DEX)-loaded core layer is fabricated using coaxial electrospinning technology, considering the temporal sequence of vascularization and bone repair. DFO acts as an angiogenesis promoter and DEX is used as an osteogenesis inducer. The results demonstrate that the early and rapid release of DFO promotes angiogenesis in human umbilical vascular endothelial cells and the sustained release of DEX enhances the osteogenic differentiation of rat bone mesenchymal stem cells. DFO and DEX exert synergetic effects on osteogenic differentiation via the Wnt/ß-catenin signaling pathway, and the dual-drug programmed releasing EFM acquired perfect vascularized bone regeneration ability in a rat calvarial defect model. Overall, the study suggests a low-cost strategy to enhance vascularized bone regeneration by adjusting the behavior of angiogenesis and osteogenesis in time dimension.

A novel multifunctional carbon aerogel-coated platform for osteosarcoma therapy and enhanced bone regeneration.

Nowadays, groundbreaking strategies are urgently needed to address drug resistance, osteolysis, bone defects and other predicaments impeding the therapeutic efficacy of osteosarcoma. Among them, photothermal therapy (PTT), using systematically administrated nanoagents, exhibits attractive therapeutic efficacy, yet is powerless in bone defect regeneration. Herein, a novel multifunctional beta-tricalcium phosphate (ß-Ca3(PO4)2, ß-TCP) bioceramic platform-coated with carbon aerogel (CA), which was initially developed for tumor therapy, was fabricated. On account of the desirable photothermal capabilities of CA, sufficient hyperthermia is generated under the irradiation of an 808 nm laser to achieve a thorough ablation of osteosarcoma tumors. Furthermore, CA-coated surfaces provide extra roughness and a higher specific surface area, which promoted the protein recruitment ability and osteogenesis via a fibronectin (FN)-mediated signaling pathway. The photothermal therapeutic efficacy and osteogenesis capability of CA-coated ß-TCP-C suggests a novel approach for the treatment of osteosarcoma and provides provoking inspiration for the prospective bio-application of CA.