Tendon injuries are often exacerbated by persistent inflammation,which hampers tissue regeneration.In this study,we developed a noninvasive,wirelessly controlled,and self-powered piezoelectric nanofilm fabricated by c...Tendon injuries are often exacerbated by persistent inflammation,which hampers tissue regeneration.In this study,we developed a noninvasive,wirelessly controlled,and self-powered piezoelectric nanofilm fabricated by coaxial electrospinning of polycaprolactone(PCL)and tetragonal barium titanate nanoparticles(BTO),and investigated its roles in modulating inflammation and repairing Achilles tendon defects as well as the mechanism in a rat model.In vitro study and in vivo study upon subcutaneous implantation showed that the piezoelectric PCL/BTO nanofilms could inhibit M1 macrophage polarization and reduce the secretion of inflammatory factors.Moreover,when bridging an Achilles tendon defect,the nanofilms could promote tenogenic gene expression including collagen deposition,and collagen remodeling,facilitate functional tendon recovery and significantly reduce tissue inflammation by suppressing M1 macrophage polarization and promoting M2 polarization.Moreover,the piezoelectric stimulation could also enhance tendon regeneration by inhibiting angiogenesis,reducing lipid deposition,and decreasing ectopic ossification.Mechanistically,the piezoelectric nanofilms reduced tissue inflammation mainly via inhibiting the nuclear factor(NF)-κB signaling pathway that is mediated by interleukin(IL)-17A secreted from CD3^(+)T cells,and thus to reduce proinflammatory factors,such as IL-1βand IL-6,inducible nitric oxide synthase,monocyte chemoattractant protein-1,and tumor necrosis factor-α.These findings indicate the potential of piezoelectric stimulation in immunomodulation,and in promoting tendon regeneration via IL-17A/NF-κB-mediated pathway.展开更多
基金supported by the National Natural Science Founda-tion of China(31870967 to Wei Liu and 81701841 to Wenbo Wang)the National Key R&D Program of China(2018YFC1105800 to Wei Liu)+1 种基金supported by the Shanghai Pujiang Program(23PJD047)the on-job postdoctoral program.
文摘Tendon injuries are often exacerbated by persistent inflammation,which hampers tissue regeneration.In this study,we developed a noninvasive,wirelessly controlled,and self-powered piezoelectric nanofilm fabricated by coaxial electrospinning of polycaprolactone(PCL)and tetragonal barium titanate nanoparticles(BTO),and investigated its roles in modulating inflammation and repairing Achilles tendon defects as well as the mechanism in a rat model.In vitro study and in vivo study upon subcutaneous implantation showed that the piezoelectric PCL/BTO nanofilms could inhibit M1 macrophage polarization and reduce the secretion of inflammatory factors.Moreover,when bridging an Achilles tendon defect,the nanofilms could promote tenogenic gene expression including collagen deposition,and collagen remodeling,facilitate functional tendon recovery and significantly reduce tissue inflammation by suppressing M1 macrophage polarization and promoting M2 polarization.Moreover,the piezoelectric stimulation could also enhance tendon regeneration by inhibiting angiogenesis,reducing lipid deposition,and decreasing ectopic ossification.Mechanistically,the piezoelectric nanofilms reduced tissue inflammation mainly via inhibiting the nuclear factor(NF)-κB signaling pathway that is mediated by interleukin(IL)-17A secreted from CD3^(+)T cells,and thus to reduce proinflammatory factors,such as IL-1βand IL-6,inducible nitric oxide synthase,monocyte chemoattractant protein-1,and tumor necrosis factor-α.These findings indicate the potential of piezoelectric stimulation in immunomodulation,and in promoting tendon regeneration via IL-17A/NF-κB-mediated pathway.
