The implantation of synthetic polymeric scaffolds induced foreign-body reaction(FBR)seriously influence the wound healing and impair functionality recovery.A novel short peptide,mechano-growth factor(MGF),was introduc...The implantation of synthetic polymeric scaffolds induced foreign-body reaction(FBR)seriously influence the wound healing and impair functionality recovery.A novel short peptide,mechano-growth factor(MGF),was introduced in this study to modify an electrospun polycaprolactone(PCL)fibrous scaffold to direct the macrophage phenotype transition and mitigate the FBR.In vitro studies discovered the cell signal transduction mechanism of MGF regulates the macrophage polarization via the expression of related genes and proteins.We found that macrophages response the MGF stimuli via endocytosis,then MGF promotes the histone acetylation and upregulates the STAT6 expression to direct an anti-inflammatory phenotype transition.Subsequently,an immunoregulatory electrospun PCL fibrous scaffold was modified by silk fibroin(SF)single-component layer-by-layer assembly,and the SF was decorated with MGF via click chemistry.Macrophages seeded on scaffold to identify the function of MGF modified scaffold in directing macrophage polarization in vitro.Parallelly,rat subcutaneous implantation model and rat tendon adhesion model were performed to detect the immunomodulatory ability of the MGF-modified scaffold in vivo.The results demonstrate that MGF-modified scaffold is beneficial to the transformation of macrophages to M2 phenotype in vitro.More importantly,MGF-functionalized scaffold can inhibit the FBR at the subcutaneous tissue and prevent tissue adhesion.展开更多
Mechano-growth factor (MGF) is a stretch sensitive factor in myocytes, and it might also be produced by other mechanocytes under mechanical stimulation. In this study, both the mRNA and protein expression of MGF were ...Mechano-growth factor (MGF) is a stretch sensitive factor in myocytes, and it might also be produced by other mechanocytes under mechanical stimulation. In this study, both the mRNA and protein expression of MGF were detected in stretched osteoblasts. Quantitative analysis showed that a cyclic stretching stimulation caused a quick and sharp increase of MGF mRNA and protein expression from a low basal level under no stretch; the mRNA and protein levels respectively peaked in 6 and 12 h to 5 and 5.2 fold over the basal level and returned to normal by 24 h. The subcellular distribution of MGF protein was revealed by immunofluorescence analysis to be restricted to the nucleus. We concluded that cyclic stretching stimulation could induce MGF expression in osteoblasts in a pulsing fashion; and the nuclear distribution of MGF suggested that MGF might act in mechanocytes as an autocrine growth factor.展开更多
基金We acknowledge the funding support from the National Natural Science Foundation of China(31971258,11532004)the 111 Project(B06023,B13003)Chongqing Postdoctoral Science Foundation(csts2019jcyj-bsh0068).
文摘The implantation of synthetic polymeric scaffolds induced foreign-body reaction(FBR)seriously influence the wound healing and impair functionality recovery.A novel short peptide,mechano-growth factor(MGF),was introduced in this study to modify an electrospun polycaprolactone(PCL)fibrous scaffold to direct the macrophage phenotype transition and mitigate the FBR.In vitro studies discovered the cell signal transduction mechanism of MGF regulates the macrophage polarization via the expression of related genes and proteins.We found that macrophages response the MGF stimuli via endocytosis,then MGF promotes the histone acetylation and upregulates the STAT6 expression to direct an anti-inflammatory phenotype transition.Subsequently,an immunoregulatory electrospun PCL fibrous scaffold was modified by silk fibroin(SF)single-component layer-by-layer assembly,and the SF was decorated with MGF via click chemistry.Macrophages seeded on scaffold to identify the function of MGF modified scaffold in directing macrophage polarization in vitro.Parallelly,rat subcutaneous implantation model and rat tendon adhesion model were performed to detect the immunomodulatory ability of the MGF-modified scaffold in vivo.The results demonstrate that MGF-modified scaffold is beneficial to the transformation of macrophages to M2 phenotype in vitro.More importantly,MGF-functionalized scaffold can inhibit the FBR at the subcutaneous tissue and prevent tissue adhesion.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 30870609 and 30600130)
文摘Mechano-growth factor (MGF) is a stretch sensitive factor in myocytes, and it might also be produced by other mechanocytes under mechanical stimulation. In this study, both the mRNA and protein expression of MGF were detected in stretched osteoblasts. Quantitative analysis showed that a cyclic stretching stimulation caused a quick and sharp increase of MGF mRNA and protein expression from a low basal level under no stretch; the mRNA and protein levels respectively peaked in 6 and 12 h to 5 and 5.2 fold over the basal level and returned to normal by 24 h. The subcellular distribution of MGF protein was revealed by immunofluorescence analysis to be restricted to the nucleus. We concluded that cyclic stretching stimulation could induce MGF expression in osteoblasts in a pulsing fashion; and the nuclear distribution of MGF suggested that MGF might act in mechanocytes as an autocrine growth factor.
基金Supported by the National Natural Science Foundation of China(30973686)Medicinal Science and Techology Research Project(BWS11J052)+3 种基金the National key scientific instrument and equipment development project(2012YQ0401400901)the National Science and Techology Major Project(2012ZX09J12201)the National Key Technology R&D Program of China(2009BAK59B01)the Foundation of State Key Laboratory of Space Medicine Fundamentals and Application,China Astronaut Research and Training Center(SMFA10B01,SMFA12B05)
