Elastomers with outstanding strength,toughness and healing efficiency are highly promising for many emerging fields.However,it is still a challenge to integrate all these beneficial features in one elastomer.Herein,an...Elastomers with outstanding strength,toughness and healing efficiency are highly promising for many emerging fields.However,it is still a challenge to integrate all these beneficial features in one elastomer.Herein,an asymmetric alicyclic structure adjacent to aromatic disulfide was tactfully introduced into the backbone of polyurethane(PU)elastomer.Specifically,such elastomer(PU-HPS)was fabricated by polycondensing polytetramethylene ether glycol(PTMEG),isophorone diisocyanate(IPDI)and p-hydroxydiphenyl disulfide(HPS)via one-pot method.The molecular mobility and phase morphology of PU-HPS can be tuned by adjusting the HPS content.Consequently,the dynamic exchange of hydrogen and disulfide bonds in the hard segment domains can also be tailored.The optimized sample manifests outstanding tensile strength(46.4 MPa),high toughness(109.1 MJ/m^(3)),high self-healing efficiency after fracture(90.3%),complete scratch recovery(100%)and good puncture resistance.Therefore,this work provides a facile strategy for developing robust self-healing polymers.展开更多
Hemophilia A is caused by a genetic mutation in coagulation factor VIII （FVIII） gene and gene therapy is considered to be a promising strategy for its treatment. We recently demonstrated that co-delivery of two vect...Hemophilia A is caused by a genetic mutation in coagulation factor VIII （FVIII） gene and gene therapy is considered to be a promising strategy for its treatment. We recently demonstrated that co-delivery of two vectors expressing M662C mutated heavy and D1828C mutated light chain genes of B-domain-deleted coagulation factor VIII （BDD-FVIII） leads to inter-chain disulfide cross-linking and improved heavy chain secretion in vitro. In this study, co-injection of both M662C and D1828C mutated BDD-FVIII gene expression vectors into mice resulted in increased heavy chain secretion and coagulation activity in plasma in vivo. Approximately （239＋_56） ng mL-1 above endogenous levels of transgenic FVIII heavy chain was found in mouse plasma using a chain-specific ELISA. For FVIII coagulation activity, approximately （1.09＋_0.25） IU mL-1 above en- dogenous levels were detected in co-injected transgenic mouse plasma using a chromogenic assay. These data demonstrate that inter-chain disulfide bonds likely increase heavy chain secretion and coagulation activity in the plasma of transgenic mice with an improved efficacy of a dual-vector delivery of BDD-FVIII gene. These findings support our ongoing efforts to develop a gene therapy for hemophilia A treatment using dual-AAV vectors.展开更多
基金supported by the National Natural Science Foundation of China(No.51873110)the Foundation of Guangdong Provincial Key Laboratory of Natural Rubber Processing and Key Laboratory of Carb on Fiber and Functio nal Polymers(Beijing University of Chemical Technology),Ministry of Educati on.
文摘Elastomers with outstanding strength,toughness and healing efficiency are highly promising for many emerging fields.However,it is still a challenge to integrate all these beneficial features in one elastomer.Herein,an asymmetric alicyclic structure adjacent to aromatic disulfide was tactfully introduced into the backbone of polyurethane(PU)elastomer.Specifically,such elastomer(PU-HPS)was fabricated by polycondensing polytetramethylene ether glycol(PTMEG),isophorone diisocyanate(IPDI)and p-hydroxydiphenyl disulfide(HPS)via one-pot method.The molecular mobility and phase morphology of PU-HPS can be tuned by adjusting the HPS content.Consequently,the dynamic exchange of hydrogen and disulfide bonds in the hard segment domains can also be tailored.The optimized sample manifests outstanding tensile strength(46.4 MPa),high toughness(109.1 MJ/m^(3)),high self-healing efficiency after fracture(90.3%),complete scratch recovery(100%)and good puncture resistance.Therefore,this work provides a facile strategy for developing robust self-healing polymers.
基金supported by the Natural Science Foundation of Shandong Province,China(Grant No.ZR2010CM061)the Scientific Research Foundation from Ministry of Education for Returned Overseas Chinese Scholars(Grant No.20071108)
文摘Hemophilia A is caused by a genetic mutation in coagulation factor VIII （FVIII） gene and gene therapy is considered to be a promising strategy for its treatment. We recently demonstrated that co-delivery of two vectors expressing M662C mutated heavy and D1828C mutated light chain genes of B-domain-deleted coagulation factor VIII （BDD-FVIII） leads to inter-chain disulfide cross-linking and improved heavy chain secretion in vitro. In this study, co-injection of both M662C and D1828C mutated BDD-FVIII gene expression vectors into mice resulted in increased heavy chain secretion and coagulation activity in plasma in vivo. Approximately （239＋_56） ng mL-1 above endogenous levels of transgenic FVIII heavy chain was found in mouse plasma using a chain-specific ELISA. For FVIII coagulation activity, approximately （1.09＋_0.25） IU mL-1 above en- dogenous levels were detected in co-injected transgenic mouse plasma using a chromogenic assay. These data demonstrate that inter-chain disulfide bonds likely increase heavy chain secretion and coagulation activity in the plasma of transgenic mice with an improved efficacy of a dual-vector delivery of BDD-FVIII gene. These findings support our ongoing efforts to develop a gene therapy for hemophilia A treatment using dual-AAV vectors.
