Unhealable diabetic wounds need to be addressed with the help of newer,more efficacious strategies.Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for ch...Unhealable diabetic wounds need to be addressed with the help of newer,more efficacious strategies.Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment.Here,the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch(SFP)were demonstrated to promote diabetic wound healing.Silk fibroin binding peptide(SFBP)was screened through phage display,and SFBP-Gluc-MS2(SGM)and pac-miR146a-pac fusion protein were constructed.The designed exosomes(SGM-Exos,miR146a-Exos,and SGM-miR146a-Exos)were isolated from the engineered placental mesenchymal stem cells(PMSCs)transduced with SGM or/and pac-miR146a-pac protein.Gluc signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of SGM-Exo.Moreover,the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in miR146a-Exos.Superior to untreated,SGM-miR146a-Exo-only treated,and SFP-only treated groups,SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation,collagen deposition,and neovascularization.The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment.Here,we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.展开更多
基金This work was supported by the National Nature Science Foundation of China(81901971,82172211,81830064,82172231)Natural Science Foundation of Beijing Municipal(7194316,7202197)+3 种基金National Key Research and Development Programs of China(2022YFA1104303)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)the Military Medical Research and Development Projects(AWS17J005,2019-126)Military Medical Science and Technology Youth Training Program(21QNPY128).
文摘Unhealable diabetic wounds need to be addressed with the help of newer,more efficacious strategies.Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment.Here,the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch(SFP)were demonstrated to promote diabetic wound healing.Silk fibroin binding peptide(SFBP)was screened through phage display,and SFBP-Gluc-MS2(SGM)and pac-miR146a-pac fusion protein were constructed.The designed exosomes(SGM-Exos,miR146a-Exos,and SGM-miR146a-Exos)were isolated from the engineered placental mesenchymal stem cells(PMSCs)transduced with SGM or/and pac-miR146a-pac protein.Gluc signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of SGM-Exo.Moreover,the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in miR146a-Exos.Superior to untreated,SGM-miR146a-Exo-only treated,and SFP-only treated groups,SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation,collagen deposition,and neovascularization.The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment.Here,we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.
