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Current clinical management primarily depends on anticoagulants. Traditional oral and injectable formulations are hindered by delayed onset, low patient compliance, and side effects. Microneedles (MNs)\u2010based transdermal delivery has emerged as a minimally invasive approach for the treatment of pulmonary embolism (PE). However, inadequate skin adhesion and low drug bioavailability continue to pose the therapeutic efficacy and convenience of anticoagulant MNs. To overcome these challenges, an innovative stepped octopus\u2010inspired architecture microneedles patch (Step\u2010OIAMNs) with high adhesion and high drug delivery efficiency was proposed here. Hyaluronic acid (HA) tip, loaded with recombinant hirudin, was positioned at the center of the methyl vinyl ether\u2010co\u2010maleic anhydride (PVM\/MA) groove, where negative pressure was generated during application. The strong adhesion of the microneedle patch, achieved through negative pressure (~35.54 kPa), effectively improves drug delivery efficiency by counteracting the skin's natural rebound. Experimental results demonstrate that Step\u2010OIAMNs not only significantly enhance transdermal drug permeation rates and blood drug concentration levels, but also exhibit excellent anticoagulant effects. In a murine acute PE model, Step\u2010MN effectively suppressed thrombus formation and increased survival rates to 80%.<\/jats:p>","DOI":"10.1002\/smll.202512693","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:10:57Z","timestamp":1786943457000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stepped Octopus\u2010Inspired Architecture Microneedles for Pulmonary Embolism Prevention"],"prefix":"10.1002","volume":"22","author":[{"given":"Shaomei","family":"Lu","sequence":"first","affiliation":[{"name":"State Key Laboratory of High\u2010Performance Tools Guangdong Provincial Key Laboratory of Minimally Invasive Surgical Instruments and Manufacturing Technology School of Electromechanical Engineering Guangdong University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of High\u2010Performance Tools Guangdong Provincial Key Laboratory of Minimally Invasive Surgical Instruments and Manufacturing Technology School of Electromechanical Engineering Guangdong University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwei","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of High\u2010Performance Tools Guangdong Provincial Key Laboratory of Minimally Invasive Surgical Instruments and Manufacturing Technology School of Electromechanical Engineering Guangdong University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of High\u2010Performance Tools Guangdong Provincial Key Laboratory of Minimally Invasive Surgical Instruments and Manufacturing Technology School of Electromechanical Engineering Guangdong University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of High\u2010Performance Tools Guangdong Provincial Key Laboratory of Minimally Invasive Surgical Instruments and Manufacturing Technology School of Electromechanical Engineering Guangdong University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Fu","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and Environment Northumbria University at Newcastle, Newcastle upon Tyne  Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Hong Gong (Macao) Limited  Macao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Chengdu Taitai Biotechnology Co., Ltd.  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