Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas
Abstract Safe and high-efficiency gene therapy for nucleus pulposus (NP) regeneration was urgently desired to treat disc degeneration-associated diseases. In this work, an efficient nonviral cationic block copolymer gene delivery system was used to deliver therapeutic plasmid DNA (pDNA), which was p...
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| Veröffentlicht in: | Biomaterials 2015-06, Vol.52, p.1-13 |
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| creator | Feng, Ganjun Chen, Hongying Li, Junjie Huang, Qiang Gupte, Melanie J Liu, Hao Song, Yueming Ge, Zhishen |
| description | Abstract Safe and high-efficiency gene therapy for nucleus pulposus (NP) regeneration was urgently desired to treat disc degeneration-associated diseases. In this work, an efficient nonviral cationic block copolymer gene delivery system was used to deliver therapeutic plasmid DNA (pDNA), which was prepared via complexation between the mixed cationic block copolymers, poly(ethylene glycol)- block -poly{ N -[ N -(2-aminoethyl)-2-aminoehtyl]aspartamide} [PEG- b -PAsp(DET)] and poly( N -isopropylacrylamide)- block -PAsp(DET) [PNIPAM- b -PAsp(DET)], and pDNA at 25 °C. The mixed polyplex micelles (MPMs) containing heterogeneous coronas with hydrophobic and hydrophilic microdomains coexisting could be obtained upon heating from 25 to 37 °C, which showed high tolerability against nuclease and strong resistance towards protein adsorption. The gene transfection efficiency of MPMs in NP cells was significantly higher than that of regular polyplex micelles prepared from sole block copolymer of PEG- b -PAsp(DET) (SPMs) in in vitro and in vivo evaluation due to the synergistic effect of improved colloidal stability and low cytotoxicity. High expression of heme oxygenase-1 (HO-1) in NP cells transfected by MPMs loading HO-1 pDNA significantly decreased the expression activity of matrix metalloproteinases 3 (MMP-3) and cyclo-oxygenase-2 (COX-2) induced by interleukin-1β (IL-1β), and simultaneously increased the NP phenotype-associated genes such as aggrecan, type II collagen, and SOX-9. Moreover, the therapeutic effects of MPMs loading pDNA were tested to treat disc degeneration induced by stab injury. The results demonstrated that administration of HO-1 pDNA carried by MPMs in rat tail discs apparently reduced inflammatory responses induced by need stab and increased glycosaminoglycan (GAG) content, finally achieving better therapeutic efficacy as compared with SPMs. Consequently, MPMs loading HO-1 pDNA were demonstrated to be potential as a safe and high-efficiency nonviral gene delivery system for retarding or regenerating the degenerative discs. |
| doi_str_mv | 10.1016/j.biomaterials.2015.02.024 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1770309795</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0142961215001349</els_id><sourcerecordid>1667963038</sourcerecordid><originalsourceid>FETCH-LOGICAL-c501t-9ccef1a18834bfb4d363b6432526d25d051414e9a4143359d763853f687096fe3</originalsourceid><addsrcrecordid>eNqNUk1v1DAQjRCILoW_gCxOXLL4OzYHpKqFglTBAThbjjNhvSRxsJN282f4rTjdghAXKo3sGeu9eTOeKYoXBG8JJvLVflv70NsJordd2lJMxBbTbPxBsSGqUqXQWDwsNphwWmpJ6EnxJKU9zjHm9HFxQoUiimO9KX5ewgBo2kG044LaENEwuw7mhMa5G0PKToRvGRPt5MOA6gXtoAcUDkt-tQlKgsbOpt436OLjGXI2Rg_Niuv9ITtj6Jaxg0MOHXQdJHTjp92tYh_KCGkMQ_LXkNPmhsIqFbKoCzHk9E-LR23uEZ7d3afF13dvv5y_L68-XX44P7sqncBkKrVz0BJLlGK8bmveMMlqyRkVVDZUNFgQTjhom0_GhG4qyZRgrVQV1rIFdlq8POYdY_gxQ5pM79Nar70tx5CqwgzrSot7QBlVBGOO_w-VstKSYaYy9PUR6mJIKUJrxuh7GxdDsFmnbvbm76mbdeoG02w8k5_f6cx1D80f6u8xZ8DFEQD5D689RJOch8FB4yO4yTTB30_nzT9pXOcH72z3HRZI-zDHYeUQkzLBfF73b10_IvLqMa7ZL43R2_A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1667963038</pqid></control><display><type>article</type><title>Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Feng, Ganjun ; Chen, Hongying ; Li, Junjie ; Huang, Qiang ; Gupte, Melanie J ; Liu, Hao ; Song, Yueming ; Ge, Zhishen</creator><creatorcontrib>Feng, Ganjun ; Chen, Hongying ; Li, Junjie ; Huang, Qiang ; Gupte, Melanie J ; Liu, Hao ; Song, Yueming ; Ge, Zhishen</creatorcontrib><description>Abstract Safe and high-efficiency gene therapy for nucleus pulposus (NP) regeneration was urgently desired to treat disc degeneration-associated diseases. In this work, an efficient nonviral cationic block copolymer gene delivery system was used to deliver therapeutic plasmid DNA (pDNA), which was prepared via complexation between the mixed cationic block copolymers, poly(ethylene glycol)- block -poly{ N -[ N -(2-aminoethyl)-2-aminoehtyl]aspartamide} [PEG- b -PAsp(DET)] and poly( N -isopropylacrylamide)- block -PAsp(DET) [PNIPAM- b -PAsp(DET)], and pDNA at 25 °C. The mixed polyplex micelles (MPMs) containing heterogeneous coronas with hydrophobic and hydrophilic microdomains coexisting could be obtained upon heating from 25 to 37 °C, which showed high tolerability against nuclease and strong resistance towards protein adsorption. The gene transfection efficiency of MPMs in NP cells was significantly higher than that of regular polyplex micelles prepared from sole block copolymer of PEG- b -PAsp(DET) (SPMs) in in vitro and in vivo evaluation due to the synergistic effect of improved colloidal stability and low cytotoxicity. High expression of heme oxygenase-1 (HO-1) in NP cells transfected by MPMs loading HO-1 pDNA significantly decreased the expression activity of matrix metalloproteinases 3 (MMP-3) and cyclo-oxygenase-2 (COX-2) induced by interleukin-1β (IL-1β), and simultaneously increased the NP phenotype-associated genes such as aggrecan, type II collagen, and SOX-9. Moreover, the therapeutic effects of MPMs loading pDNA were tested to treat disc degeneration induced by stab injury. The results demonstrated that administration of HO-1 pDNA carried by MPMs in rat tail discs apparently reduced inflammatory responses induced by need stab and increased glycosaminoglycan (GAG) content, finally achieving better therapeutic efficacy as compared with SPMs. Consequently, MPMs loading HO-1 pDNA were demonstrated to be potential as a safe and high-efficiency nonviral gene delivery system for retarding or regenerating the degenerative discs.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2015.02.024</identifier><identifier>PMID: 25818409</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Acrylic Resins - chemistry ; Advanced Basic Science ; Animals ; Block copolymers ; Cationic ; Cells, Cultured ; Cervical Vertebrae - metabolism ; Cervical Vertebrae - physiology ; Coronas ; Dentistry ; Discs ; DNA - administration & dosage ; DNA - genetics ; DNA - therapeutic use ; Gene expression ; Gene Expression Regulation ; Gene therapy ; Genes ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; Genetic Vectors - genetics ; Genetic Vectors - therapeutic use ; Heme Oxygenase-1 - genetics ; Micelles ; Nonviral gene carrier ; Nuclei ; Nucleus pulposus regeneration ; Plasmids - administration & dosage ; Plasmids - genetics ; Plasmids - therapeutic use ; Polyplex micelles ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Temperature ; Thermo-responsive ; Transfection</subject><ispartof>Biomaterials, 2015-06, Vol.52, p.1-13</ispartof><rights>Elsevier Ltd</rights><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-9ccef1a18834bfb4d363b6432526d25d051414e9a4143359d763853f687096fe3</citedby><cites>FETCH-LOGICAL-c501t-9ccef1a18834bfb4d363b6432526d25d051414e9a4143359d763853f687096fe3</cites><orcidid>0000-0002-2668-6974</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0142961215001349$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25818409$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Ganjun</creatorcontrib><creatorcontrib>Chen, Hongying</creatorcontrib><creatorcontrib>Li, Junjie</creatorcontrib><creatorcontrib>Huang, Qiang</creatorcontrib><creatorcontrib>Gupte, Melanie J</creatorcontrib><creatorcontrib>Liu, Hao</creatorcontrib><creatorcontrib>Song, Yueming</creatorcontrib><creatorcontrib>Ge, Zhishen</creatorcontrib><title>Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Safe and high-efficiency gene therapy for nucleus pulposus (NP) regeneration was urgently desired to treat disc degeneration-associated diseases. In this work, an efficient nonviral cationic block copolymer gene delivery system was used to deliver therapeutic plasmid DNA (pDNA), which was prepared via complexation between the mixed cationic block copolymers, poly(ethylene glycol)- block -poly{ N -[ N -(2-aminoethyl)-2-aminoehtyl]aspartamide} [PEG- b -PAsp(DET)] and poly( N -isopropylacrylamide)- block -PAsp(DET) [PNIPAM- b -PAsp(DET)], and pDNA at 25 °C. The mixed polyplex micelles (MPMs) containing heterogeneous coronas with hydrophobic and hydrophilic microdomains coexisting could be obtained upon heating from 25 to 37 °C, which showed high tolerability against nuclease and strong resistance towards protein adsorption. The gene transfection efficiency of MPMs in NP cells was significantly higher than that of regular polyplex micelles prepared from sole block copolymer of PEG- b -PAsp(DET) (SPMs) in in vitro and in vivo evaluation due to the synergistic effect of improved colloidal stability and low cytotoxicity. High expression of heme oxygenase-1 (HO-1) in NP cells transfected by MPMs loading HO-1 pDNA significantly decreased the expression activity of matrix metalloproteinases 3 (MMP-3) and cyclo-oxygenase-2 (COX-2) induced by interleukin-1β (IL-1β), and simultaneously increased the NP phenotype-associated genes such as aggrecan, type II collagen, and SOX-9. Moreover, the therapeutic effects of MPMs loading pDNA were tested to treat disc degeneration induced by stab injury. The results demonstrated that administration of HO-1 pDNA carried by MPMs in rat tail discs apparently reduced inflammatory responses induced by need stab and increased glycosaminoglycan (GAG) content, finally achieving better therapeutic efficacy as compared with SPMs. Consequently, MPMs loading HO-1 pDNA were demonstrated to be potential as a safe and high-efficiency nonviral gene delivery system for retarding or regenerating the degenerative discs.</description><subject>Acrylic Resins - chemistry</subject><subject>Advanced Basic Science</subject><subject>Animals</subject><subject>Block copolymers</subject><subject>Cationic</subject><subject>Cells, Cultured</subject><subject>Cervical Vertebrae - metabolism</subject><subject>Cervical Vertebrae - physiology</subject><subject>Coronas</subject><subject>Dentistry</subject><subject>Discs</subject><subject>DNA - administration & dosage</subject><subject>DNA - genetics</subject><subject>DNA - therapeutic use</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Gene therapy</subject><subject>Genes</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Genetic Vectors - genetics</subject><subject>Genetic Vectors - therapeutic use</subject><subject>Heme Oxygenase-1 - genetics</subject><subject>Micelles</subject><subject>Nonviral gene carrier</subject><subject>Nuclei</subject><subject>Nucleus pulposus regeneration</subject><subject>Plasmids - administration & dosage</subject><subject>Plasmids - genetics</subject><subject>Plasmids - therapeutic use</subject><subject>Polyplex micelles</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Regeneration</subject><subject>Temperature</subject><subject>Thermo-responsive</subject><subject>Transfection</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUk1v1DAQjRCILoW_gCxOXLL4OzYHpKqFglTBAThbjjNhvSRxsJN282f4rTjdghAXKo3sGeu9eTOeKYoXBG8JJvLVflv70NsJordd2lJMxBbTbPxBsSGqUqXQWDwsNphwWmpJ6EnxJKU9zjHm9HFxQoUiimO9KX5ewgBo2kG044LaENEwuw7mhMa5G0PKToRvGRPt5MOA6gXtoAcUDkt-tQlKgsbOpt436OLjGXI2Rg_Niuv9ITtj6Jaxg0MOHXQdJHTjp92tYh_KCGkMQ_LXkNPmhsIqFbKoCzHk9E-LR23uEZ7d3afF13dvv5y_L68-XX44P7sqncBkKrVz0BJLlGK8bmveMMlqyRkVVDZUNFgQTjhom0_GhG4qyZRgrVQV1rIFdlq8POYdY_gxQ5pM79Nar70tx5CqwgzrSot7QBlVBGOO_w-VstKSYaYy9PUR6mJIKUJrxuh7GxdDsFmnbvbm76mbdeoG02w8k5_f6cx1D80f6u8xZ8DFEQD5D689RJOch8FB4yO4yTTB30_nzT9pXOcH72z3HRZI-zDHYeUQkzLBfF73b10_IvLqMa7ZL43R2_A</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Feng, Ganjun</creator><creator>Chen, Hongying</creator><creator>Li, Junjie</creator><creator>Huang, Qiang</creator><creator>Gupte, Melanie J</creator><creator>Liu, Hao</creator><creator>Song, Yueming</creator><creator>Ge, Zhishen</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0002-2668-6974</orcidid></search><sort><creationdate>20150601</creationdate><title>Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas</title><author>Feng, Ganjun ; Chen, Hongying ; Li, Junjie ; Huang, Qiang ; Gupte, Melanie J ; Liu, Hao ; Song, Yueming ; Ge, Zhishen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-9ccef1a18834bfb4d363b6432526d25d051414e9a4143359d763853f687096fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acrylic Resins - chemistry</topic><topic>Advanced Basic Science</topic><topic>Animals</topic><topic>Block copolymers</topic><topic>Cationic</topic><topic>Cells, Cultured</topic><topic>Cervical Vertebrae - metabolism</topic><topic>Cervical Vertebrae - physiology</topic><topic>Coronas</topic><topic>Dentistry</topic><topic>Discs</topic><topic>DNA - administration & dosage</topic><topic>DNA - genetics</topic><topic>DNA - therapeutic use</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Gene therapy</topic><topic>Genes</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors - administration & dosage</topic><topic>Genetic Vectors - genetics</topic><topic>Genetic Vectors - therapeutic use</topic><topic>Heme Oxygenase-1 - genetics</topic><topic>Micelles</topic><topic>Nonviral gene carrier</topic><topic>Nuclei</topic><topic>Nucleus pulposus regeneration</topic><topic>Plasmids - administration & dosage</topic><topic>Plasmids - genetics</topic><topic>Plasmids - therapeutic use</topic><topic>Polyplex micelles</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Regeneration</topic><topic>Temperature</topic><topic>Thermo-responsive</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Ganjun</creatorcontrib><creatorcontrib>Chen, Hongying</creatorcontrib><creatorcontrib>Li, Junjie</creatorcontrib><creatorcontrib>Huang, Qiang</creatorcontrib><creatorcontrib>Gupte, Melanie J</creatorcontrib><creatorcontrib>Liu, Hao</creatorcontrib><creatorcontrib>Song, Yueming</creatorcontrib><creatorcontrib>Ge, Zhishen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Ganjun</au><au>Chen, Hongying</au><au>Li, Junjie</au><au>Huang, Qiang</au><au>Gupte, Melanie J</au><au>Liu, Hao</au><au>Song, Yueming</au><au>Ge, Zhishen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>52</volume><spage>1</spage><epage>13</epage><pages>1-13</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract Safe and high-efficiency gene therapy for nucleus pulposus (NP) regeneration was urgently desired to treat disc degeneration-associated diseases. In this work, an efficient nonviral cationic block copolymer gene delivery system was used to deliver therapeutic plasmid DNA (pDNA), which was prepared via complexation between the mixed cationic block copolymers, poly(ethylene glycol)- block -poly{ N -[ N -(2-aminoethyl)-2-aminoehtyl]aspartamide} [PEG- b -PAsp(DET)] and poly( N -isopropylacrylamide)- block -PAsp(DET) [PNIPAM- b -PAsp(DET)], and pDNA at 25 °C. The mixed polyplex micelles (MPMs) containing heterogeneous coronas with hydrophobic and hydrophilic microdomains coexisting could be obtained upon heating from 25 to 37 °C, which showed high tolerability against nuclease and strong resistance towards protein adsorption. The gene transfection efficiency of MPMs in NP cells was significantly higher than that of regular polyplex micelles prepared from sole block copolymer of PEG- b -PAsp(DET) (SPMs) in in vitro and in vivo evaluation due to the synergistic effect of improved colloidal stability and low cytotoxicity. High expression of heme oxygenase-1 (HO-1) in NP cells transfected by MPMs loading HO-1 pDNA significantly decreased the expression activity of matrix metalloproteinases 3 (MMP-3) and cyclo-oxygenase-2 (COX-2) induced by interleukin-1β (IL-1β), and simultaneously increased the NP phenotype-associated genes such as aggrecan, type II collagen, and SOX-9. Moreover, the therapeutic effects of MPMs loading pDNA were tested to treat disc degeneration induced by stab injury. The results demonstrated that administration of HO-1 pDNA carried by MPMs in rat tail discs apparently reduced inflammatory responses induced by need stab and increased glycosaminoglycan (GAG) content, finally achieving better therapeutic efficacy as compared with SPMs. Consequently, MPMs loading HO-1 pDNA were demonstrated to be potential as a safe and high-efficiency nonviral gene delivery system for retarding or regenerating the degenerative discs.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>25818409</pmid><doi>10.1016/j.biomaterials.2015.02.024</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-2668-6974</orcidid></addata></record> |
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| subjects | Acrylic Resins - chemistry Advanced Basic Science Animals Block copolymers Cationic Cells, Cultured Cervical Vertebrae - metabolism Cervical Vertebrae - physiology Coronas Dentistry Discs DNA - administration & dosage DNA - genetics DNA - therapeutic use Gene expression Gene Expression Regulation Gene therapy Genes Genetic Therapy - methods Genetic Vectors - administration & dosage Genetic Vectors - genetics Genetic Vectors - therapeutic use Heme Oxygenase-1 - genetics Micelles Nonviral gene carrier Nuclei Nucleus pulposus regeneration Plasmids - administration & dosage Plasmids - genetics Plasmids - therapeutic use Polyplex micelles Rabbits Rats Rats, Sprague-Dawley Regeneration Temperature Thermo-responsive Transfection |
| title | Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas |
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