It remains a major challenge to simultaneously achieve bone regeneration and prevent infection in the complex microenvironment of repairing bone defects. Here, we developed a novel ECM-mimicking scaffold by coaxial electrospinning to be endowed with multibiological functions. Lysophosphatidic acid (LPA) and zinc oxide (ZnO) nanoparticles were loaded into the poly-lactic-co-glycolic acid/polycaprolactone (PLGA/PCL, PP) sheath layer of coaxial nanofibers, and deferoxamine (DFO) nanoparticles were loaded into its core layer. The novel scaffold PP-LPA-ZnO/DFO maintained a porous nanofibrous architecture after incorporating three active nanoparticles, showing better physicochemical properties and eximious biocompatibility. In vitro studies showed that the bio-scaffold loaded with LPA nanoparticles had excellent cell adhesion, proliferation, and differentiation for MC3T3-E1 cells and synergistic osteogenesis with the addition of ZnO and DFO nanoparticles. Further, the PP-LPA-ZnO/DFO scaffold promoted tube formation and facilitated the expression of vascular endothelial markers in HUVECs. In vitro antibacterial studies against Escherichia Coli and Staphylococcus aureus demonstrated effective antibacterial activity of the PP-LPA-ZnO/DFO scaffold. In vivo studies showed that the PP-LPA-ZnO/DFO scaffold exhibited excellent biocompatibility after subcutaneous implantation and remarkable osteogenesis at 4 weeks postimplantation in the mouse alveolar bone defects. Importantly, the PP-LPA-ZnO/DFO scaffold showed significant antibacterial activity, prominent neovascularization, and new bone formation in the rat fenestration defect model. Overall, the spatially sustained release of LPA, ZnO, and DFO nanoparticles through the coaxial scaffold synergistically enhanced biocompatibility, osteogenesis, angiogenesis, and effective antibacterial properties, which is ultimately beneficial for bone regeneration. This project provides the optimized design of bone regenerative biomaterials and a new strategy for bone regeneration, especially in the potentially infected microenvironment.
Surface heparinization is an effective solution to resolve low endothelialization, poor anticoagulation, and hemocompatibility of polyurethane (PU) used as materials of small‐diameter vascular grafts. Here, the effects of polydopamine (PDA) and poly (acrylic acid) (PAA) as crosslinking agents on the surface heparinization were explored. The PU membranes grafted with heparin (Hep) via dopamine (PU/PDA‐Hep) showed better hydrophilicity and stability, compared to heparinized PU membranes via acrylic acid (PU/PAA‐Hep). The results of X‐ray photoelectron spectroscopy demonstrated that heparin was successfully grafted onto the PU surface and the grafting efficiency was high when PDA as a cross‐linking agent. The grafted heparin aggregated and formed nanoparticles, and increased the surface roughness of PU membranes. The heparinized membranes demonstrated good anti‐adhesion of bovine serum albumin and fibrin protein. In addition, no activated platelets or educts on heparinized PU were found by platelet adhesion tests, implying that heparin‐immobilized surfaces had good hemocompatibility. Moreover, the in vitro cytocompatibility assessment showed that the PU/PDA‐Hep significantly improved the proliferation of L929 cells and was superior to PU/AA‐Hep. These results demonstrated that PDA‐assisted surface heparinization was an effective method to improve the anticoagulant and biocompatibility of PU small‐diameter vascular materials and could be extended to other implantable materials.
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