Immune response is an important factor in determining the fate of bone replacement materials,in which macrophages play an important role.It is a new idea to design biomaterials with immunomodulatory function to reduce...Immune response is an important factor in determining the fate of bone replacement materials,in which macrophages play an important role.It is a new idea to design biomaterials with immunomodulatory function to reduce inflammation and promote bone integration by regulating macrophages polarization.In this work,the immunomodulatory properties of CaP Zn-Mn-Li alloys and the specific mechanism of action were investigated.We found that the CaP Zn0.8Mn0.1Li alloy promoted the polarization of macrophages toward M2 and reduced inflammation,which could effectively upregulate osteogenesis-related factors and promote new bone formation,indicating the important role of macrophages polarization in biomaterial induction of osteogenesis.In vivo studies further demonstrated that CaP Zn0.8Mn0.1Li alloy could stimulate osteogenesis better than other Zn-Mn-Li alloys implantations by regulating macrophages polarization and reducing inflammation.In addition,transcriptome results showed that CaP Zn0.8Mn0.1Li played an important regulatory role in the life process of macrophages,activating Toll-like receptor signaling pathway,which participated in the activation and attenuation of inflammation,and accelerated bone integration.Thus,by preparing CaP coatings on the surface of Zn-Mn-Li alloys and combining the bioactive ingredient with controlled release,the biomaterial will be imbibed with beneficial immunomodulatory properties that promote bone integration.展开更多
Bone immune responses based on macrophages are critical in the osteogenesis of bone abnormalities.In general,M2 macrophage facilitate the promotion of osteogenesis,as well,M1 macrophage play an important role in early...Bone immune responses based on macrophages are critical in the osteogenesis of bone abnormalities.In general,M2 macrophage facilitate the promotion of osteogenesis,as well,M1 macrophage play an important role in early bone healing,as confirmed by previous studies.However,it is not clear how M1 macrophage are involved in the bone immune response.MiR-21a-5p is a highly expressed microRNA in M1 macrophage in contrast to M2.Therefore,the current work sought to ascertain the influence of M1 macrophage on bone healing via exosomal miR-21a-5p and the probable mechanism.We discovered that injecting M1 macrophage exosomes overexpressing miR-21a-5p into bone defect locations enhanced bone regeneration in vivo.Furthermore,by directly targeting GATA2,miR-21a-5p accelerated MC3T3-E1 osteogenic differentiation.Our findings showed that exosomal miR-21a-5p from M1 macrophage may be transported to osteoblasts and target GATA2 to enhance bone defect healing.展开更多
基金supported by the Science Foundation of Shandong Province of China[Grant No.ZR2021MH026,ZR2022MH075]Medicine and Health Science Technology Development plan of Shandong Province of China[Grant No.202108020440,2020Q127]+1 种基金Liaocheng Key Research and Development Plan of Shandong Province of China[Grant No.2022YDSF16,2022YDSF21]Liaocheng People’s Hospital Youth Fund Project[Grant No.LYQN201914].
文摘Immune response is an important factor in determining the fate of bone replacement materials,in which macrophages play an important role.It is a new idea to design biomaterials with immunomodulatory function to reduce inflammation and promote bone integration by regulating macrophages polarization.In this work,the immunomodulatory properties of CaP Zn-Mn-Li alloys and the specific mechanism of action were investigated.We found that the CaP Zn0.8Mn0.1Li alloy promoted the polarization of macrophages toward M2 and reduced inflammation,which could effectively upregulate osteogenesis-related factors and promote new bone formation,indicating the important role of macrophages polarization in biomaterial induction of osteogenesis.In vivo studies further demonstrated that CaP Zn0.8Mn0.1Li alloy could stimulate osteogenesis better than other Zn-Mn-Li alloys implantations by regulating macrophages polarization and reducing inflammation.In addition,transcriptome results showed that CaP Zn0.8Mn0.1Li played an important regulatory role in the life process of macrophages,activating Toll-like receptor signaling pathway,which participated in the activation and attenuation of inflammation,and accelerated bone integration.Thus,by preparing CaP coatings on the surface of Zn-Mn-Li alloys and combining the bioactive ingredient with controlled release,the biomaterial will be imbibed with beneficial immunomodulatory properties that promote bone integration.
基金supported by the Science Foundation of Shandong Province of China(Grant Nos ZR2021MH026,ZR2022MH075,ZR2020MH100)Shandong Province Medical and Health Science and Technology Development Plan(2018WS426)+1 种基金Liaocheng Key Research and Development Plan of Shandong Province of China(Grant Nos 2022YDSF16,2022YDSF21)Liaocheng People’s Hospital Youth Fund Project(Grant No.LYQN201914).
文摘Bone immune responses based on macrophages are critical in the osteogenesis of bone abnormalities.In general,M2 macrophage facilitate the promotion of osteogenesis,as well,M1 macrophage play an important role in early bone healing,as confirmed by previous studies.However,it is not clear how M1 macrophage are involved in the bone immune response.MiR-21a-5p is a highly expressed microRNA in M1 macrophage in contrast to M2.Therefore,the current work sought to ascertain the influence of M1 macrophage on bone healing via exosomal miR-21a-5p and the probable mechanism.We discovered that injecting M1 macrophage exosomes overexpressing miR-21a-5p into bone defect locations enhanced bone regeneration in vivo.Furthermore,by directly targeting GATA2,miR-21a-5p accelerated MC3T3-E1 osteogenic differentiation.Our findings showed that exosomal miR-21a-5p from M1 macrophage may be transported to osteoblasts and target GATA2 to enhance bone defect healing.
