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Although nanoparticle\u2010mediated electrospun fibers enable sustainable gene silencing, low efficiency, loss of biological activity, toxicity issues, and complex electrospinning techniques are all bottlenecks of these systems. Preventing peritendinous adhesion is crucial for their successful use, which involves blocking cellular signaling via physical barriers. Here, a multifunctional, yet structurally simple, cationic 2,6\u2010pyridinedicarboxaldehyde\u2010polyethylenimine (PDA)\u2010mediated extracellular signal\u2010regulated kinase (ERK)2\u2010siRNA polymeric delivery system is reported, in the form of peritendinous antiadhesion electrospun poly\u2010<jats:sc>l<\/jats:sc>\u2010lactic acid\/hyaluronan membranes (P\/H), with the ability to perform sustained release of bioactive siRNA for long\u2010term prevention of adhesions and ERK2 silencing. After 4 days of culture, the cell area and proliferation rate of chicken embryonic fibroblasts on siRNA+PDA+P\/H membrane are significantly less than those on P\/H and siRNA+P\/H membranes. The in vivo results of average optical density of collagen type III (Col III) and gene expression of ERK2 and its downstream SMAD3 in the siRNA+PDA+P\/H group are less than those of P\/H and siRNA+P\/H groups. Consequently, siRNA+PDA+P\/H electrospun membrane can protect the bioactivity of ERK2\u2010siRNA and release it in a sustained manner. Moreover, adhesion formation is inhibited by reducing fibroblast proliferation and Col III deposition, and downregulating ERK2 and its downstream SMAD3.<\/jats:p>","DOI":"10.1002\/advs.201801217","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T02:53:44Z","timestamp":1542768824000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Gene Silencing via PDA\/ERK2\u2010siRNA\u2010Mediated Electrospun Fibers for Peritendinous Antiadhesion"],"prefix":"10.1002","volume":"6","author":[{"given":"Shen","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital  600 Yishan Road Shanghai 200233 China"},{"name":"Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin 2nd Road Shanghai 200025 China"}]},{"given":"Fei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai Jiao Tong University  800 Dongchuan Road Shanghai 200240 China"}]},{"given":"Shanshan","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai Jiao Tong University  800 Dongchuan Road Shanghai 200240 China"}]},{"given":"Tianyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital  600 Yishan Road Shanghai 200233 China"}]},{"given":"Shun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital  600 Yishan Road Shanghai 200233 China"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai Jiao Tong University  800 Dongchuan Road Shanghai 200240 China"}]},{"given":"Chongyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital  600 Yishan Road Shanghai 200233 China"}]},{"given":"Guanlan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Laboratory \u00c5bo Akademi University  20520 Turku Finland"}]},{"given":"Tuo","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai Jiao Tong University  800 Dongchuan Road Shanghai 200240 China"}]},{"given":"Wenguo","family":"Cui","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin 2nd Road Shanghai 200025 China"},{"name":"State Key Laboratory of Molecular Engineering of Polymers Fudan University  No. 220 Handan Road Shanghai 200433 China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5763-7553","authenticated-orcid":false,"given":"Bruno","family":"Sarmento","sequence":"additional","affiliation":[{"name":"I3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Rua Alfredo Allen, 208 Porto 4200\u2010135 Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica Universidade do Porto  Rua Alfredo Allen, 208 Porto 4200\u2010135 Portugal"},{"name":"CESPU\u2014Instituto de Investiga\u00e7\u00e3o e Forma\u00e7\u00e3o Avan\u00e7ada em Ci\u00eancias e Tecnologias da Sa\u00fade  Rua Central de Gandra 1317 Gandra 4585\u2010116 Portugal"}]},{"given":"Lianfu","family":"Deng","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin 2nd Road Shanghai 200025 China"}]},{"given":"Cunyi","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital  600 Yishan Road Shanghai 200233 China"}]}],"member":"311","published-online":{"date-parts":[[2018,11,20]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"221","volume":"487","author":"Heidenreich O.","year":"2009","journal-title":"Methods Mol. 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