{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:32:38Z","timestamp":1772555558144,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,8,31]],"date-time":"2019-08-31T00:00:00Z","timestamp":1567209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R15EB022345"],"award-info":[{"award-number":["R15EB022345"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1451514"],"award-info":[{"award-number":["1451514"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Neutrophils, the first cells that interact with surface-adsorbed proteins on biomaterials, have been increasingly recognized as critical maestros in the foreign body response for guided tissue regeneration. Recent research has shown that small diameter (SD) fibers of electrospun tissue regeneration templates, which have a high surface area to volume ratio (SAVR), enhance the release of neutrophil extracellular traps (NETs) compared to large diameter (LD) fibers, resulting in impaired tissue regeneration. In this study, we evaluated the adsorption of eight human serum proteins on the surface of electrospun templates to investigate how protein adsorption may regulate the release of NETs. Electrospun polydioxanone templates made from SD fibers with high SAVR and LD fibers with low SAVR, were incubated with 0.2% human serum and in situ protein adsorption was quantified with infrared-based immunodetection. Of the detected proteins, IgM and vitronectin adsorbed at low levels, suggesting that they do not play a central role in the release of NETs. Contrastingly, albumin and IgG adsorbed rapidly to the surface of the templates. One-hundred to 200 times more IgG adsorbed on the templates compared to albumin, with significantly greater adsorption occurring on the SD templates with high SAVR. Given that neutrophils express receptors that interact with IgG during phagocytosis and NET release, these results suggest that SAVR-dependent adsorption of IgG on the SD electrospun templates may contribute to the up-regulated release of NETs. Overall, this study may aid in the design of immunomodulatory biomaterials that regulate NET release and thus the potential for neutrophil-driven tissue regeneration.<\/jats:p>","DOI":"10.3390\/bioengineering6030078","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T03:16:12Z","timestamp":1567394172000},"page":"78","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Surface Area to Volume Ratio of Electrospun Polydioxanone Templates Regulates the Adsorption of Soluble Proteins from Human Serum"],"prefix":"10.3390","volume":"6","author":[{"given":"Allison E.","family":"Fetz","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina A.","family":"Fantaziu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marko Z.","family":"Radic","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0917-8203","authenticated-orcid":false,"given":"Gary L.","family":"Bowlin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/0039-6028(69)90037-5","article-title":"Findings with the recording ellipsometer suggesting rapid exchange of specific plasma proteins at liquid\/solid interfaces","volume":"16","author":"Vroman","year":"1969","journal-title":"Surf. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.2174\/156802608783790901","article-title":"Surface chemistry influences implant biocompatibility","volume":"8","author":"Tang","year":"2008","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/rb\/rbw041","article-title":"An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration","volume":"4","author":"Selders","year":"2017","journal-title":"Regen. Biomater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.smim.2007.11.004","article-title":"Foreign body reaction to biomaterials","volume":"20","author":"Anderson","year":"2008","journal-title":"Semin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nature12175","article-title":"Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo","volume":"498","author":"Afonso","year":"2013","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nri.2016.49","article-title":"Neutrophil migration in infection and wound repair: Going forward in reverse","volume":"16","author":"Rosowski","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20262","DOI":"10.1073\/pnas.0706438104","article-title":"Human neutrophils uniquely release TIMP-free MMP-9 to provide a potent catalytic stimulator of angiogenesis","volume":"104","author":"Ardi","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nm.1959","article-title":"Netting neutrophils in autoimmune small-vessel vasculitis","volume":"15","author":"Kessenbrock","year":"2009","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1096\/fasebj.30.1_supplement.50.1","article-title":"Neutrophil extracellular traps dive bleomycin-induced lung fibrosis by regulating TGF\u03b21-dependent interactions of platelets and macrophages","volume":"30","author":"Riehl","year":"2016","journal-title":"FASEB J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8674","DOI":"10.1073\/pnas.1301059110","article-title":"Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice","volume":"110","author":"Martinod","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vitkov, L., Krautgartner, W.D., Obermayer, A., Stoiber, W., Hannig, M., Klappacher, M., and Hartl, D. (2015). The initial inflammatory response to bioactive implants is characterized by NETosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121359"},{"key":"ref_13","first-page":"E5856","article-title":"Nanoparticles size-dependently initiate self-limiting NETosis-driven inflammation","volume":"113","author":"Bilyy","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1089\/ten.tea.2016.0452","article-title":"Electrospun template architecture and composition regulate neutrophil NETosis in vitro and in vivo","volume":"23","author":"Fetz","year":"2017","journal-title":"Tissue Eng. Part A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.biomaterials.2006.09.006","article-title":"Volumetric interpretation of protein adsorption: Competition from mixtures and the Vroman effect","volume":"28","author":"Noh","year":"2007","journal-title":"Biomaterials"},{"key":"ref_16","unstructured":"Busher, J.T. (1990). Serum Albumin and Globulin. Clinical Methods: The History, Physical, and Laboratory Examinations, Butterworths. [3rd ed.]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/0049-3848(84)90259-7","article-title":"Fibronectin and coagulation factor XIII increases blood platelet adhesion to fibrin","volume":"34","author":"Hansen","year":"1984","journal-title":"Thromb. Res."},{"key":"ref_18","unstructured":"Janeway, C.A., Travers, P., Walport, M., and Shlomchik, M.J. (2001). The complement system and innate immunity. Immunobiology: The Immune System in Health and Disease, Garland Science. [5th ed.]."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.0022-202X.2005.23673.x","article-title":"C1q: Its functions within the innate and adaptive immune responses and its role in lupus autoimmunity","volume":"125","author":"Sontheimer","year":"2005","journal-title":"J. Invest. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1034\/j.1600-065X.2001.1800103.x","article-title":"Structure and biology of complement protein C3, a connecting link between innate and acquired immunity","volume":"180","author":"Sahu","year":"2001","journal-title":"Immunol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.1384129","article-title":"Inhibition of neutrophil chemokinesis on vitronectin by inhibitors of calcineurin","volume":"258","author":"Hendey","year":"1992","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7079","DOI":"10.4049\/jimmunol.179.10.7079","article-title":"Involvement of vitronectin in lipopolysaccaride-induced acute lung injury","volume":"179","author":"Tsuruta","year":"2007","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1165\/rcmb.2011-0187OC","article-title":"Vitronectin inhibits neutrophil apoptosis through activation of integrin-associated signaling pathways","volume":"46","author":"Bae","year":"2012","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4049\/jimmunol.94.1.84","article-title":"Quantitative determination of serum immunoglobulins in antibody-agar plates","volume":"94","author":"Fahey","year":"1965","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1242\/jcs.02411","article-title":"Matrix cell adhesion activation by non-adhesion proteins","volume":"118","author":"Koblinski","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1083\/jcb.122.1.243","article-title":"Albumin inhibits neutrophil spreading and hydrogen peroxide release by blocking the shedding of CD43 (sialophorin, leukosialin)","volume":"122","author":"Nathan","year":"1993","journal-title":"J. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fimmu.2019.00012","article-title":"Serum and serum albumin inhibit in vitro formation of neutrophil extracellular traps (NETs)","volume":"10","author":"Neubert","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_28","first-page":"42","article-title":"Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities","volume":"151","author":"Alende","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1006\/jcis.1996.0156","article-title":"Adsorption dynamics of IgG and Its F (ab\u2032)2 and Fc fragments studied by reflectometry","volume":"178","author":"Buijs","year":"1996","journal-title":"J. Colloid Interface Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0166-6622(90)80128-Q","article-title":"The behavior of some model proteins at solid\u2014liquid interfaces 2. Sequential and competitive adsorption","volume":"51","author":"Arai","year":"1990","journal-title":"Colloids Surf."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0304-4165(01)00101-5","article-title":"Adsorption of IgG onto hydrophobic Teflon. Differences between the Fab and Fc domains","volume":"1526","author":"Vermeer","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1385\/IR:29:1-3:219","article-title":"Functional regulation of human neutrophil Fc \u03b3 receptors","volume":"29","author":"Selvaraj","year":"2004","journal-title":"Immunol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/1044-5323(95)90006-3","article-title":"Function of human Fc\u03b3RIIA and Fc\u03b3RIIIB","volume":"7","author":"Unkeless","year":"1995","journal-title":"Semin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1182\/blood.V95.3.1069.003k14_1069_1077","article-title":"Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function","volume":"95","author":"Nagarajan","year":"2000","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.15190\/d.2014.11","article-title":"Characterization of rapid neutrophil extracellular trap formation and its cooperation with phagocytosis in human neutrophils","volume":"2","author":"Saffarzadeh","year":"2014","journal-title":"Discoveries"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1084\/jem.20161512","article-title":"TLR8 activation shifts neutrophils from phagocytosis to NETosis through furin-dependent shedding of FcgRIIA","volume":"214","author":"Lood","year":"2017","journal-title":"J. Exp. Med."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/6\/3\/78\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:15:37Z","timestamp":1760188537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/6\/3\/78"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,31]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["bioengineering6030078"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering6030078","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,31]]}}}