{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:51:24Z","timestamp":1785847884362,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["51971236"],"award-info":[{"award-number":["51971236"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Shanghai Rising-Star Program","award":["21QA1410400"],"award-info":[{"award-number":["21QA1410400"]}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["21S31901200"],"award-info":[{"award-number":["21S31901200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Youth Innovation Promotion Association of the Chinese Academy of Sciences","award":["2020254"],"award-info":[{"award-number":["2020254"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Physical features on the biomaterial surface are known to affect macrophage cell shape and phenotype, providing opportunities for the design of novel \u201cimmune-instructive\u201d topographies to modulate foreign body response. The work presented here employed nanopatterned polydimethylsiloxane substrates with well-characterized nanopillars and nanopits to assess RAW264.7 macrophage response to feature size. Macrophages responded to the small nanopillars (SNPLs) substrates (450 nm in diameter with average 300 nm edge-edge spacing), resulting in larger and well-spread cell morphology. Increasing interpillar distance to 800 nm in the large nanopillars (LNPLs) led to macrophages exhibiting morphologies similar to being cultured on the flat control. Macrophages responded to the nanopits (NPTs with 150 nm deep and average 800 nm edge-edge spacing) by a significant increase in cell elongation. Elongation and well-spread cell shape led to expression of anti-inflammatory\/pro-healing (M2) phenotypic markers and downregulated expression of inflammatory cytokines. SNPLs and NPTs with high availability of integrin binding region of fibronectin facilitated integrin \u03b21 expression and thus stored focal adhesion formation. Increased integrin \u03b21 expression in macrophages on the SNPLs and NTPs was required for activation of the PI3K\/Akt pathway, which promoted macrophage cell spreading and negatively regulated NF-\u03baB activation as evidenced by similar globular cell shape and higher level of NF-\u03baB expression after PI3K blockade. These observations suggested that alterations in macrophage cell shape from surface nanotopographies may provide vital cues to orchestrate macrophage phenotype.<\/jats:p>","DOI":"10.3390\/jfb13010031","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T03:34:13Z","timestamp":1647401653000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Engineering Nanopatterned Structures to Orchestrate Macrophage Phenotype by Cell Shape"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-4836","authenticated-orcid":false,"given":"Kai","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Shao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China"},{"name":"Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youtao","family":"Xie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhen","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nmat2442","article-title":"Understanding biophysicochemical interactions at the nano-bio interface","volume":"8","author":"Nel","year":"2009","journal-title":"Nat. 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