Dental pulp stem cell-derived extracellular matrix: autologous tool boosting bone regeneration

<!DOCTYPE html> <html lang="en" class="pb-page" data-request-id="597a434d-e527-4f33-b4a8-9861f97fd124" ><head data-pb-dropzone="head"><meta name="pbContext" content=";article:article:pii\:S1465324922000482;ctype:string:Journal Content;requestedJournal:journal:jcyt;website:website:jcyt-site;page:string:Access Denial;subPage:string:Access Denial;issue:issue:pii\:S1465324922X00066;pageGroup:string:Article View;journal:journal:jcyt;wgroup:string:Migrated Websites;product:product:elsevier\:product\:ha"/>  <meta name="robots" content="noarchive,nocache" /> <meta name="viewport" content=""width=device-width,initial-scale=1,maximum-scale=1, user-scalable=1"/> <meta property="og:title" content="Dental pulp stem cell-derived extracellular matrix: autologous tool boosting bone regeneration" /> <meta property="og:type" content="Article" /> <meta property="og:url" content="https://www.isct-cytotherapy.org/article/S1465-3249(22)00048-2/abstract" /> <meta property="og:site_name" content="Cytotherapy" /> <meta property="og:image" content="https://www.isct-cytotherapy.org/cms/asset/9025d2c7-6fa9-4679-9286-5c65865c9690/ga1.jpg" /> <meta property="og:description" content="To facilitate artificial bone construct integration into a patient's body, scaffolds are enriched with different biologically active molecules. Among various scaffold decoration techniques, coating surfaces with cell-derived extracellular matrix (ECM) is a rapidly growing field of research. In this study, for the first time, this technology was applied using primary dental pulp stem cells (DPSCs) and tested for use in artificial bone tissue construction." /> <meta name="twitter:title" content="Dental pulp stem cell-derived extracellular matrix: autologous tool boosting bone regeneration" /> <meta name="twitter:image" content="https://www.isct-cytotherapy.org/cms/asset/9025d2c7-6fa9-4679-9286-5c65865c9690/ga1.jpg" /> <meta name="twitter:description" content="To facilitate artificial bone construct integration into a patient's body, scaffolds are enriched with different biologically active molecules. Among various scaffold decoration techniques, coating surfaces with cell-derived extracellular matrix (ECM) is a rapidly growing field of research. In this study, for the first time, this technology was applied using primary dental pulp stem cells (DPSCs) and tested for use in artificial bone tissue construction." /> <meta name="twitter:card" content="summary_large_image"> <link rel="canonical" href="https://www.isct-cytotherapy.org/article/S1465-3249(22)00048-2/abstract"> <title>Dental pulp stem cell-derived extracellular matrix: autologous tool boosting bone regeneration - Cytotherapy</title><meta name="citation_journal_title" content="Cytotherapy"/> <meta name="citation_journal_abbrev" content="Cytotherapy"/> <meta name="citation_publisher" content="Elsevier"/> <meta name="citation_title" content="Dental pulp stem cell-derived extracellular matrix: autologous tool boosting bone regeneration"/> <meta name="citation_date" content="2022/06/01"/> <meta name="citation_online_date" content="2022/03/15"/> <meta name="citation_volume" content="24"/> <meta name="citation_issue" content="6"/> <meta name="citation_firstpage" content="597"/> <meta name="citation_lastpage" content="607"/> <meta name="citation_pmid" content="35304075"/> <meta name="citation_abstract_html_url" content="http://www.isct-cytotherapy.org/article/S1465324922000482/abstract"/> <meta name="citation_fulltext_html_url" content="http://www.isct-cytotherapy.org/article/S1465324922000482/fulltext"/> <meta name="citation_pdf_url" content="http://www.isct-cytotherapy.org/article/S1465324922000482/pdf"/> <meta name="citation_issn" content="1465-3249"/> <meta name="citation_language" content="English"/> <meta name="citation_doi" content="10.1016/j.jcyt.2022.02.002"/> <meta name="citation_pmid" content="35304075"/> <meta name="citation_author" content="Milda Alksne"></meta><meta name="citation_author_email" content="milda.peciukaityte@gf.vu.lt"></meta><meta name="citation_author_orcid" content="0000-0003-0448-4770"></meta><meta name="citation_author_institution" content="Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania"></meta><meta name="citation_author" content="Migle Kalvaityte"></meta><meta name="citation_author_orcid" content="0000-0003-3435-132X"></meta><meta name="citation_author_institution" content="Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania"></meta><meta name="citation_author" content="Egidijus Simoliunas"></meta><meta name="citation_author_institution" content="Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania"></meta><meta name="citation_author" content="Ieva Gendviliene"></meta><meta name="citation_author_institution" content="Institute of Odontology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania"></meta><meta name="citation_author" content="Povilas Barasa"></meta><meta name="citation_author_institution" content="Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania"></meta><meta name="citation_author" content="Ieva Rinkunaite"></meta><meta name="citation_author_orcid" content="0000-0001-9956-4022"></meta><meta name="citation_author_institution" content="Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania"></meta><meta name="citation_author" content="Algirdas Kaupinis"></meta><meta name="citation_author_orcid" content="0000-0003-3157-6670"></meta><meta name="citation_author_institution" content="Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania"></meta><meta name="citation_author" content="Dmitrij Seinin"></meta><meta name="citation_author_institution" content="National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania"></meta><meta name="citation_author" content="Vygandas Rutkunas"></meta><meta name="citation_author_institution" content="Institute of Odontology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania"></meta><meta name="citation_author" content="Virginija Bukelskiene"></meta><meta name="citation_author_institution" content="Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania"></meta><meta name="citation_keywords" content="bone; bone regeneration; dental pulp stem cell-derived extracellular matrix; dental pulp stem cells; extracellular matrix"></meta><meta name="citation_reference" content="citation_title=Bone tissue regeneration: biology, strategies and interface studies; citation_author=M. 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Imai; citation_journal_title=Am. J. Respir. Crit. Care Med.; citation_volume=187; citation_firstpage=65; citation_lastpage=77; citation_publication_date=2013; "></meta><meta name="citation_abstract" content="<h2>Abstract</h2><h3>Background aims</h3><p>To facilitate artificial bone construct integration into a patient's body, scaffolds are enriched with different biologically active molecules. Among various scaffold decoration techniques, coating surfaces with cell-derived extracellular matrix (ECM) is a rapidly growing field of research. In this study, for the first time, this technology was applied using primary dental pulp stem cells (DPSCs) and tested for use in artificial bone tissue construction.</p><h3>Methods</h3><p>Rat DPSCs were grown on three-dimensional-printed porous polylactic acid scaffolds for 7 days. After the predetermined time, samples were decellularized, and the remaining ECM detailed proteomic analysis was performed. Further, DPSC-secreated ECM impact to mesenchymal stromal cells (MSC) behaviour as well as its role in osteoregeneration induction were analysed.</p><h3>Results</h3><p>It was identified that DPSC-specific ECM protein network ornamenting surface-enhanced MSC attachment, migration and proliferation and even promoted spontaneous stem cell osteogenesis. This protein network also demonstrated angiogenic properties and did not stimulate MSCs to secrete molecules associated with scaffold rejection. With regard to bone defects, DPSC-derived ECM recruited endogenous stem cells, initiating the bone self-healing process. Thus, the DPSC-secreted ECM network was able to significantly enhance artificial bone construct integration and induce successful tissue regeneration.</p><h3>Conclusions</h3><p>DPSC-derived ECM can be a perfect tool for decoration of various biomaterials in the context of bone tissue engineering.</p>"></meta><meta charset="UTF-8" /> <script type="text/javascript"> ;window.NREUM||(NREUM={});NREUM.init={privacy:{cookies_enabled:true}}; window.NREUM||(NREUM={}),__nr_require=function(t,e,n){function r(n){if(!e[n]){var o=e[n]={exports:{}};t[n][0].call(o.exports,function(e){var o=t[n][1][e];return r(o||e)},o,o.exports)}return e[n].exports}if("function"==typeof __nr_require)return __nr_require;for(var o=0;o<n.length;o++)r(n[o]);return r}({1:[function(t,e,n){function r(t){try{c.console&&console.log(t)}catch(e){}}var o,i=t("ee"),a=t(26),c={};try{o=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof 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Account</a></div></div></div></div></div></div> <div role="dialog" aria-modal="true" aria-label="Reset password" class="popup top-drawer request-reset-password-drawer hidden"><div class="content"><a href="#" aria-label="Close reset password popup" title="Close reset password popup" role="button" class="close"><i class="icon-close_thin"></i></a><div class="request-reset"><div class="form"><p class="sub">If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password</p><div tabindex="-1" class="message error"></div><form action="/action/requestResetPassword" method="post" class="request-reset-password-form"><input type="hidden" name="platform"/><input type="hidden" name="requestResetPassword" value="true"/><input type="hidden" name="codeSite" value="jcyt-site"/><div class="input-group"><div class="label"><label for="reset-password-email">Email*</label></div><input id="reset-password-email" type="text" name="email" value="" size="15" class="email"/></div><div class="submit"><input type="submit" name="submit" value="Submit" disabled="disabled" class="button primary submit"/></div></form></div><div class="success-template hidden"><p>If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password</p></div></div><div class="request-reset-cancel"><a href="#" aria-label="Close reset password popup" title="Close reset password popup" class="cancel">Cancel</a></div></div></div> <div class="ux3-ads"> <div class="pb-ad">    <div id="gpt-Variables" data-adfile="JBS"> <input type="hidden" id="gptSite" value="jcyt"> <input type="hidden" id="gptLoggedIn" value="no"> <input type="hidden" id="gptAccessType" value="ae:ANON_GUEST|ae:ANON_GUEST"> </div> <div id="gpt-Interscroller" class="gpt-InScrollBox" style="display:none;"> <div class="gpt-InScrollLabel">ADVERTISEMENT</div> <div class="gpt-InScrollContainer"> <div class="gpt-InScrollWrapper"> <div class="gpt-InScrollInner"> <div class="gpt-adinterscroller" data-adsize="interscroller"></div> </div> </div> </div> <div class="gpt-InScrollLabel">SCROLL TO CONTINUE WITH CONTENT</div> </div> <div id="gpt-DebugDiv" class="gpt-DebugDiv" style="display:none;"> <div style="width: 100%; display: table;"> <div style="display: table-row"> <div style="width: 200px; display: table-cell;"> <button class="gpt-DebugBtn" onclick="gpt_ShowConsole()">Open GPT Console</button><br /> <button id="gpt_GrapeShotDebugBtn" class="gpt-DebugBtn" onclick="gpt_GrapeShotDebug();">Open Oracle Keywords</button><br /> <br /> <button class="gpt-DebugBtn" onclick="gpt_LoadDebugValues()">Refresh Values</button> </div> <div style="display: table-cell;"> <table class="gpt-DebugTable"> <thead> <tr> <th>Property</th> <th>Value</th> </tr> </thead> <tbody> <tr><td class="gpt-DebugTitle">Status</td><td><div class="gptStatus_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Version</td><td><div class="gptVersion_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Ad File</td><td><div class="gptAdFile_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Disable Ads Flag</td><td><div class="gptDisableAds_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Environment</td><td><div class="gptTestENV_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Moat Init</td><td><div class="gptMoatInit_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Moat Ready</td><td><div class="gptMoatReady_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Contextual Ready</td><td><div class="gptContextualReady_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Contextual URL</td><td><div class="gptContextualURL_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Contextual Initial Segments</td><td><div class="gptContextualInit_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Contextual Used Segments</td><td><div class="gptContextualResult_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">AdUnit</td><td><div class="gptSite_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">SubAdUnit</td><td><div class="gptPage_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Custom Targeting</td><td><div class="gptCustomTargeting_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Ad Events</td><td><div class="gptEvent_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Invalid Ad Sizes</td><td><div class="gptInvalidAdSize_Debug"></div></td></tr> </tbody> </table> </div> </div> </div> </div> <style type="text/css"> .gpt-DebugBtn { display: inline-block; text-align: center; text-decoration: none; margin: 2px 0; border: solid 1px #122b40; border-radius: 0.4em; padding: 0.5em 1em; color: #ffffff; background-color: #204d74; font-weight: normal; font-size: 12px; } .gpt-DebugDiv { margin: 5px; } .gpt-DebugTitle { font-weight: bold; } .gpt-DebugTable { border: 1px solid #dddddd; border-collapse: collapse; margin: 5px; font-size: 0.9em; font-family: sans-serif; min-width: 400px; margin-bottom: 25px; } .gpt-DebugTable td:first-child { padding: 5px; } .gpt-DebugTable thead tr th { background-color: #d9edf7; color: #ffffff; text-align: left; padding: 5px; border-bottom: 2px solid #204d74; } .gpt-DebugTable th, .gpt-DebugTable td { padding: 5px; } .gpt-DebugTable tbody tr { border-bottom: 1px solid #dddddd; } .gpt-DebugTable tbody tr:nth-of-type(even) { background-color: #f3f3f3; } .gpt-DebugTable tbody tr:last-of-type { border-bottom: 2px solid #204d74; } .gpt-InScrollLabel { background-color: rgb(0, 0, 0); color: rgb(255, 255, 255); position: relative; max-width: 100vw; left: 50%; right: 50%; margin-left: -50vw; margin-right: -50vw; padding: 0; text-align: center; width: 100vw !important; font-size: 10px; } .gpt-InScrollBox { height: 100vh !important; width: 100vw; cursor: pointer; max-width: 100vw; position: relative; left: 50%; right: 50%; margin-left: -50vw; margin-right: -50vw; margin-bottom: 50px; padding-top: 5px; padding-bottom: 5px; z-index: 10001; background-color: white; } .gpt-InScrollBox .gpt-InScrollContainer { height: 95vh !important; position: relative; } .gpt-InScrollBox .gpt-InScrollWrapper { position: absolute !important; top: 0 !important; left: 0; width: 100%; height: 95vh !important; border: 0 !important; margin: 0 !important; padding: 0 !important; clip: rect(0, auto, auto, 0) !important; -webkit-clip-path: polygon(0px 0px, 100% 0px, 100% 100%, 0px 100%) !important; clip-path: polygon(0px 0px, 100% 0px, 100% 100%, 0px 100%) !important; } .gpt-InScrollBox .gpt-InScrollInner { position: fixed !important; top: 0 !important; left: 0 !important; bottom: 0; margin: auto; width: 100vw; height: 95vh; -webkit-transform: translateZ(0) !important; display: -webkit-box; display: -ms-flexbox; display: flex; -webkit-box-orient: vertical; -webkit-box-direction: normal; -ms-flex-direction: column; flex-direction: column; -webkit-box-align: center; -ms-flex-align: center; align-items: center; -webkit-box-pack: center; -ms-flex-pack: center; justify-content: center; text-align: center; } </style> <script class="optanon-category-4" type="text/plain"> //-------------------------------------------------------------------------- var gpt_Version = '04072023'; var gpt_AdFile = $('#gpt-Variables').data('adfile'); var gpt_MaxMOATInitAttempts = 11; var gpt_MaxMOATReadyAttempts = 11; var gpt_MaxContextualReadyAttempts = 21; var gpt_MOATInitAttempts = 0; var gpt_MOATReadyAttempts = 0; var gpt_ContextualReadyAttempts = 0; var gpt_IsProd = true; var gpt_StartTime; var gs_channels = 'DEFAULT'; var gpt_ContextualReady = false; var gpt_ContextualURL = 'Not enabled outside of Production'; var gpt_DisableAdsFlagFound = false; var gptEvent_Debug = ''; var gptCustomTargeting_Debug = ''; var gptSite_Debug = ""; var gptPage_Debug = ""; var gptContextualEnabled = false; var gptContextualResult_Debug = ''; var gptContextualInit_Debug = ''; var gptContextualURL_Debug = ''; var gptContextualReady_Debug = ''; var gptMoatReady_Debug = ''; var gptMoatInit_Debug = ''; var gptTestENV_Debug = ''; var gptDisableAds_Debug = ''; var gptStatus_Debug = 'GPT Still Loading - Refresh Values'; var gptInvalidAdSize_Debug = ''; //-------------------------------------------------------------------------- $(document).ready(function () { //Check to see if we are on a development env gpt_CheckEnvironment(); if (!gpt_DisableAdsFlagFound) { gpt_StartTime = new Date(); if (gpt_AdFile !== "PU") { //Once the dom has loaded, begin the process to init the ads. gpt_InitScripts(); gpt_CheckForMOATInit(); } } }); </script> <script type="text/javascript"> function gpt_CheckEnvironment() { if ($('#gptDisableAds').length > 0) { gptDisableAds_Debug = 'Flag Detected - Ads Disabled'; gpt_DisableAdsFlagFound = true; } else { gptDisableAds_Debug = 'Ads Enabled'; gpt_DisableAdsFlagFound = false; } switch (gpt_AdFile) { case 'PU': gptContextualEnabled = true; if ($("#Environment").val() !== "Prod") { gpt_IsProd = false; gptTestENV_Debug = 'Test Environment Detected'; } else { gptTestENV_Debug = 'Production Environment Detected'; } break; case 'JBS': case 'LANCET': gptContextualEnabled = true; if ($(".gpt-ad").length > 0) { //Other ads exist, allow the Prestitial $(document.body).append("<div class='gpt-ad' data-adsize='prestitial'></div>"); } if (window.location.hostname.toLowerCase().indexOf('.literatumonline.') >= 0) { gpt_IsProd = false; gptTestENV_Debug = 'Test Environment Detected'; } else { gptTestENV_Debug = 'Production Environment Detected'; } break; default: //Cell gptContextualEnabled = false; if (window.location.hostname.toLowerCase().indexOf('.literatumonline.') >= 0) { gpt_IsProd = false; gptTestENV_Debug = 'Test Environment Detected'; } else { gptTestENV_Debug = 'Production Environment Detected'; } break; } } //-------------------------------------------------------------------------- function gpt_GetNonCMEArticle() { var url; $('.articleCitation').each(function (i, obj) { if ($(obj).find('.toc__item__detials').length > 0) { var itemDetails = $(obj).first().find('.toc__item__detials'); var cmeFound = 0; if (cmeFound == 0) { cmeFound = $(itemDetails).find("img[title~='CME']").length; } if (cmeFound == 0) { cmeFound = $(itemDetails).find("img[title~='(CME)']").length; } if (cmeFound == 0) { cmeFound = $(itemDetails).find("img[title~='Education']").length; } if (cmeFound == 0) { cmeFound = $(itemDetails).find("img[title~='education']").length; } if (cmeFound == 0) { var itemLink = $(itemDetails).first().find('.toc__item__title'); var linkCount = $(itemLink).first().find("a:contains('CME')").length; if (linkCount == 0) { url = $(itemLink).first().find('a').attr('href'); return false; //Found a URL, break the loop } } } }); return url; } //-------------------------------------------------------------------------- function gpt_GetElapsedTime() { var endTime = new Date(); var timeDiff = endTime - gpt_StartTime; //in ms // strip the ms timeDiff /= 1000; // get seconds return seconds = Math.round(timeDiff) + " seconds"; } //-------------------------------------------------------------------------- function gpt_CheckSSC() { //Check for ScreenShot Client var gpt_SSC = gpt_GetQuerystring('gpt_ssc', ''); if (gpt_SSC == '1') { //it's the ScreenShotClient, disable MOAT IVT Detection $('#gpt-Variables').append('<input type="hidden" id="gptm_data">'); $('#gptm_data').val(0); gpt_Target("m_data"); } } //-------------------------------------------------------------------------- function gpt_LocalSS(adTypeId) { window.scrollTo(0, 0); gpt_Sleep(1000); gpt_ScrollToAd(adTypeId); gpt_PreTearsheet(adTypeId); } //-------------------------------------------------------------------------- function gpt_InitScripts() { if (gpt_AdFile == "PU") { if (gpt_IsProd) { gpt_ContextualURL = gpt_CheckForNULL($('#canonicalurl').val()); if (gpt_ContextualURL === null) { gpt_ContextualURL = window.location.href.split('?')[0].split('#')[0]; } else { gpt_ContextualURL = window.location.origin + gpt_ContextualURL; } var useSSL = 'https:' == document.location.protocol; var gs = document.createElement('script'); gs.async = true; gs.type = 'text/javascript'; gs.src = (useSSL ? 'https:' : 'http:') + '//elsevier.gscontxt.net/multizone/channels.cgi?url=' + encodeURIComponent(gpt_ContextualURL); gs.onload = function () { gpt_ContextualReady = true; }; document.head.appendChild(gs); } } else { //JBS-Cell-Lancet var useSSL = 'https:' == document.location.protocol; var gads = document.createElement('script'); gads.async = true; gads.type = 'text/javascript'; gads.src = (useSSL ? 'https:' : 'http:') + '//securepubads.g.doubleclick.net/tag/js/gpt.js'; document.head.appendChild(gads); if (gpt_IsProd && gptContextualEnabled) { gpt_ContextualURL = window.location.href.split('?')[0].split('#')[0]; var gs = document.createElement('script'); gs.async = true; gs.type = 'text/javascript'; gs.src = (useSSL ? 'https:' : 'http:') + '//elsevier.gscontxt.net/multizone/channels.cgi?url=' + encodeURIComponent(gpt_ContextualURL); gs.onload = function () { gpt_ContextualReady = true; }; document.head.appendChild(gs); } var elsevierMoatHeader = document.createElement('link'); elsevierMoatHeader.rel = 'preload'; elsevierMoatHeader.as = 'script'; elsevierMoatHeader.src = (useSSL ? 'https:' : 'http:') + '//z.moatads.com/elsevierheader150204004183/moatheader.js'; document.head.appendChild(elsevierMoatHeader); var elsevierMoatAds = document.createElement('link'); elsevierMoatAds.rel = 'preconnect'; elsevierMoatAds.src = (useSSL ? 'https:' : 'http:') + '//mb.moatads.com'; document.head.appendChild(elsevierMoatAds); var moatHeader = document.createElement('script'); moatHeader.async = true; gads.type = 'text/javascript'; moatHeader.src = (useSSL ? 'https:' : 'http:') + '//z.moatads.com/elsevierheader150204004183/moatheader.js'; document.head.appendChild(moatHeader); } } //-------------------------------------------------------------------------- async function gpt_CheckForMOATInit() { //Check every 1/10 of a second until MOAT is Loaded or 1 second timeout if (gpt_MOATInitAttempts < gpt_MaxMOATInitAttempts) { gpt_MOATInitAttempts += 1; if (typeof window.moatPrebidApi === "object") { //MOAT LOADED gptMoatInit_Debug = '0.0' + gpt_MOATInitAttempts + ' seconds'; gpt_CheckForMOATReady(); } else { setTimeout(() => { gpt_CheckForMOATInit(); }, 100); } } else { //TIMEOUT: MOAT Not LOADED gptMoatInit_Debug = 'Timeout Expired'; var googletag = googletag || {}; googletag.cmd = googletag.cmd || []; gpt_CheckForContextualReady(); } } //-------------------------------------------------------------------------- function gpt_CheckForMOATReady() { //Check every 1/10 of a second until MOAT is Ready or 1 second timeout if (gpt_MOATReadyAttempts < gpt_MaxMOATReadyAttempts) { gpt_MOATReadyAttempts += 1; if (window.moatPrebidApi.safetyDataAvailable()) { //MOAT Ready gptMoatReady_Debug = '0.0' + gpt_MOATReadyAttempts + " seconds"; gpt_CheckForContextualReady(); } else { setTimeout(() => { gpt_CheckForMOATReady(); }, 100); } } else { //TIMEOUT: MOAT Not Ready gptMoatReady_Debug = 'Timeout Expired'; gpt_CheckForContextualReady(); } } //-------------------------------------------------------------------------- function gpt_CheckForContextualReady() { //Check every 1/10 of a second until Contextual is Ready or 2 second timeout if (gpt_IsProd && gptContextualEnabled) { //Enabled if (gpt_ContextualReadyAttempts < gpt_MaxContextualReadyAttempts) { gpt_ContextualReadyAttempts += 1; if (gpt_ContextualReady) { //Contextual Ready gptContextualURL_Debug = gpt_ContextualURL; gptContextualReady_Debug = '0.0' + gpt_ContextualReadyAttempts + " seconds"; gptContextualInit_Debug = gs_channels; gpt_InitAds(); } else { setTimeout(() => { gpt_CheckForContextualReady(); }, 100); } } else { //LOG TIMEOUT error //REMOVE FOR NOW (SHOULD LOG TO A DIFF LOCATION) //TIMEOUT: Contextual Not Ready $('#gpt_GrapeShotDebugBtn').remove(); gptContextualURL_Debug = gpt_ContextualURL; gptContextualReady_Debug = 'Timeout Expired'; gptContextualInit_Debug = ""; gpt_InitAds(); } } else { //Not Enabled $('#gpt_GrapeShotDebugBtn').remove(); switch (gpt_AdFile) { case 'PU': case 'LANCET': case 'JBS': gptContextualURL_Debug = 'Not enabled outside of Production'; gptContextualReady_Debug = 'Not enabled outside of Production'; gptContextualInit_Debug = 'Not enabled outside of Production'; break; case "CELLJOURNAL": case "CELLBUCKET": gptContextualReady_Debug = 'Not enabled on Cell'; gptContextualInit_Debug = 'Not enabled on Cell'; gptContextualURL_Debug = 'Not enabled on Cell'; break; } gpt_InitAds(); } } //-------------------------------------------------------------------------- function GPT_GetPageByURL() { var host = window.location.host.toLocaleLowerCase() var localpath = window.location.pathname.toLocaleLowerCase(); ///Check for Cell.com if (host.indexOf('cell.com') >= 0) { return null; } ///Check for Cell.com (marlin-stag) if (host.indexOf('www-cell-com') >= 0) { return null; } ///Check for Lancet if (host.indexOf('thelancet') >= 0) { return null; } if (localpath.indexOf('/article/') >= 0) { return 'article.fulltext'; } if (localpath.indexOf('/action/dosearch') >= 0) { return 'search.searchResults'; } if (localpath.indexOf('/content/') >= 0) { return 'periodical.editorial'; } return 'periodical.home'; } //-------------------------------------------------------------------------- function gpt_CheckForNULL(x, valueifnull) { if (typeof valueifnull == "undefined") { valueifnull = null; } if (typeof x == 'undefined') { return valueifnull; } if (x == null) { return valueifnull; } if (x == "null") { return valueifnull; } if ($.trim(x) == '') { return valueifnull; } return x; } //-------------------------------------------------------------------------- function gpt_GetAdditionalTargeting() { //adds page level targeting of custom variables //the id (minus gpt) and the value will be used as a key-value pair //eg: <input type="hidden" id="gptissuepii" value="x" class="gpt-Target"> //eg: target issuepii=x $(".gpt-Target").each(function (index) { var gptTargetId = $(this).attr('id'); gptTargetId = gptTargetId.replace('gpt', '').toLowerCase(); if (gptTargetId !== '') { gpt_Target(gptTargetId); } }) } //-------------------------------------------------------------------------- function gpt_GetQuerystring(key, default_) { //function to read querystring variables if (default_ === null) default_ = ''; key = key.replace(/[\[]/, "\\\[").replace(/[\]]/, "\\\]"); var regex = new RegExp("[\\?&]" + key + "=([^&#]*)"); var qs = regex.exec(window.location.href); if (qs === null) return default_; else return qs[1]; } //-------------------------------------------------------------------------- function gpt_GetDFPTestId() { //Get any request for a test id from querystring and set custom targeting parameter var gptDFPTestId = gpt_GetQuerystring('dfptestid', ''); if (gptDFPTestId !== '') { $('#gpt-Variables').append('<input type="hidden" id="gptDFPTestId">'); $('#gptDFPTestId').val(gptDFPTestId); gpt_Target("DFPTestId"); } } //-------------------------------------------------------------------------- function gpt_Target(targetName) { //Set page level target if value is found if ($('#gpt' + targetName).length > 0) { var targetValue = $('#gpt' + targetName).val(); if (targetValue !== '') { targetValue = targetValue.replace(/[^-a-z0-9]/ig, ''); //Only Allow a-z, 0-9 googletag.pubads().setTargeting(targetName.toLowerCase(), targetValue.toLowerCase()); gptCustomTargeting_Debug = gptCustomTargeting_Debug + targetName.toLowerCase() + ' = ' + targetValue.toLowerCase() + '<br>'; } } } //-------------------------------------------------------------------------- function gpt_TargetAccessType() { var currentAccessType = $('#gptAccessType').val(); if (typeof currentAccessType == "undefined") { currentAccessType = ""; } if (currentAccessType.indexOf('ANON_IP') >= 0) { googletag.pubads().setTargeting("loggedin", "yes"); } else { gpt_Target("LoggedIn"); } } //-------------------------------------------------------------------------- async function gpt_PreTearsheet(adTypeId) { if (typeof adTypeId === "undefined") { adTypeId = 0; } //Remove Elsevier Cookie Policy Notice if ($("#onetrust-consent-sdk").length > 0) { $("#onetrust-consent-sdk").remove(); } //Mobile Nav $('#skip').remove(); $('#skipNavigationLink').remove(); //JBS Modals if ($('.leadinModal').length > 0) { $('.leadinModal').remove(); } if ($('.leadinModal').length > 0) { $('.leadinModal').remove(); } if ($('.usabilla__overlay').length > 0) { $('.usabilla__overlay').remove(); } //Pendo if ($('._pendo-step-container').length > 0) { $('._pendo-step-container').remove(); } if ($('._pendo-guide-tt_').length > 0) { $('._pendo-guide-tt_').remove(); } if ($('._pendo-image').length > 0) { $('._pendo-image').remove(); } if ($('._pendo-badge-image').length > 0) { $('._pendo-badge-image').remove(); } switch (gpt_AdFile) { case "CELLJOURNAL": case "CELLBUCKET": //Mobile Bug Fix on Cell if (parseInt(adTypeId) == 5) { $('.widget-horizontalAd').css('position', 'static'); $('.body-horizontalAd').css('display', 'block'); } break; case "JBS": case "LANCET": objLeaderboard = ".container-leaderboard"; offset = 53; switch (parseInt(adTypeId)) { case 3: //MPU case 4: //SkyScraper //BUGFIX: Show Sidebar ad for JBS //skyscraper & mpu if ($('.widget-verticalAd').length > 0) { $('.widget-verticalAd').css('display', 'block'); } $('#backgroundLayer').css('display', 'none'); //Hide any Prestitial break; case 6: //Prestitial $('#backgroundLayer').css('display', 'block'); break; default: $('#backgroundLayer').css('display', 'none'); //Hide any Prestitial break; } break; } } //-------------------------------------------------------------------------- function gpt_Sleep(ms) { return new Promise(resolve => setTimeout(resolve, ms)); } //-------------------------------------------------------------------------- async function gpt_ScrollToAd(adTypeId) { if (typeof adTypeId === "undefined") { adTypeId = 0; } var adId = ""; var offset = 0; var objLeaderboard = ""; var gpt_ScrollToAd = true; switch (gpt_AdFile) { case "PU": //PracticeUpdate var hideOtherAds = true; $('#modalPrestitial').modal('hide'); $('.jumbotron-welcome').hide(); objLeaderboard = ".container-leaderboard"; offset = 53; switch (parseInt(adTypeId)) { case 2: //LeaderBoard, no Scroll Needed gpt_ScrollToAd = false; adId = "adSlot1"; break; case 3: //MPU adId = "adSlot2"; break; case 4: //SkyScraper adId = "adSlot3"; $('.most-read').hide(); break; case 5: //Mobile, no Scroll Needed gpt_ScrollToAd = false; adId = "adSlot1"; break; case 6: //Interstitial gpt_ScrollToAd = false; adId = "adSlot15"; await gpt_Sleep(1000); $(objLeaderboard).hide(); $('#modalPrestitial').unbind(); $('#modalPrestitial').modal(); break; case 7: //Native Ad break; case 10: //Master Companion hideOtherAds = false; gpt_ScrollToAd = false; break; default: //Unknown Ad Type gpt_ScrollToAd = false; adId = "adSlot1"; break; } if (hideOtherAds) { //Hide all other ads $('.ad-container').each(function (i, obj) { if (this.id !== adId) { var tempParent = this.id; tempParent = tempParent.replace("adSlot", "adParent"); $("#" + tempParent).addClass('hide'); } }); } break; case "JBS": objLeaderboard = ".js__adToHide"; offset = 80; switch (parseInt(adTypeId)) { case 2: //Leaderboard gpt_ScrollToAd = false; $(".widget-verticalAd").hide(); break; case 5: //Mobile //Scroll to Top gpt_ScrollToAd = false; break; case 3: //MPU case 4: //SkyScraper $(objLeaderboard).hide(); adId = $('.gpt-ad-defined[data-adsize="sidebar"').attr('id'); break; case 10: //MasterCompanion gpt_ScrollToAd = false; break; case 13: //Phone - Portrait case 14: //Phone - Landscape $(objLeaderboard).hide(); offset = 60; adId = 'gpt-Interscroller'; gpt_ScrollToAd = true; break; default: //Unknown Ad Type gpt_ScrollToAd = false; break; } break; case "CELLJOURNAL": case "CELLBUCKET": objLeaderboard = ".js__adToHide"; offset = 260; switch (parseInt(adTypeId)) { case 2: //Leaderboard gpt_ScrollToAd = false; $('.body-verticalAd').hide(); break; case 5: //Mobile //Scroll to Top gpt_ScrollToAd = false; break; case 3: //MPU case 4: //SkyScraper $(objLeaderboard).hide(); adId = $('.gpt-ad-defined[data-adsize="boombox"').attr('id'); break; case 10: //MasterCompanion gpt_ScrollToAd = false; break; default: //Unknown Ad Type gpt_ScrollToAd = false; break; } //Hide the second ad if found var tCount = 0; $(".widget.literatumAd.none.GPT-ad-placeholder.widget-horizontalAd.widget-compact-all").each(function (index) { tCount += 1; if (tCount !== 1) { $(this).hide(); } }); break; case "LANCET": objLeaderboard = ".js__adToHide"; offset = 80; switch (parseInt(adTypeId)) { case 2: //Leaderboard gpt_ScrollToAd = false; $('.body-verticalAd').hide(); break; case 5: //Mobile //Scroll to Top gpt_ScrollToAd = false; break; case 3: //MPU case 4: //SkyScraper $(objLeaderboard).hide(); adId = $('.gpt-ad-defined[data-adsize="skyscraper"').attr('id'); break; case 10: //MasterCompanion gpt_ScrollToAd = false; break; default: //Unknown Ad Type gpt_ScrollToAd = false; break; } break; } //Scroll to Top var gpt_container = $("html,body"); gpt_container.animate({ scrollTop: 0, scrollLeft: 0 }); if (gpt_ScrollToAd) { //If Adexists, scroll to it var gpt_scrollTo = $('#' + adId); if (gpt_scrollTo.length > 0) { //Scroll to the Ad var gpt_topPosition = gpt_scrollTo.offset().top - gpt_container.offset().top + gpt_container.scrollTop(); if (gpt_topPosition > 0) { gpt_container.animate({ scrollTop: gpt_topPosition, scrollLeft: 0 }); if (gpt_topPosition - offset > 0 && offset > 0) { gpt_container.animate({ scrollTop: gpt_topPosition - offset, scrollLeft: 0 }); } } } } } //-------------------------------------------------------------------------- async function gpt_CheckForCookiePolicy() { var returnVal = false; if ($('#onetrust-accept-btn-handler').length > 0) { $('#onetrust-accept-btn-handler').click(); returnVal = true; } return returnVal; } //-------------------------------------------------------------------------- function gpt_InitAds() { var gpt_ResponsiveHomepage = false; switch (gpt_AdFile) { case "JBS": case "CELLJOURNAL": case "CELLBUCKET": //Responsive Check if ($('#hdrHomeBrand').length > 0) { gpt_ResponsiveHomepage = true; } break; } //InterScroller Check if (gpt_AdFile === "JBS") { var gpt_InterScrollerEnabled = false; var gpt_InterScrollerInsertObj; if ($("#articleHeader").length > 0) { //It's an article Page if ($('.article__sections > section').length > 0) { gpt_InterScrollerEnabled = true; gpt_InterScrollerInsertObj = $(".article__sections > section"); } } else { if ($('.toc__section').length > 0) { //It's a TOC Page gpt_InterScrollerEnabled = true; gpt_InterScrollerInsertObj = $(".toc__section").first(); } } //Add the Interscroller if (gpt_InterScrollerEnabled) { gpt_InterScrollerInsertObj.first().append($("#gpt-Interscroller").clone()); $("#gpt-Interscroller").remove(); $(".gpt-adinterscroller").addClass("gpt-ad"); } } googletag.cmd.push(function () { var gptBoomBoxSizeMapping; var gptFluidMapping; var gptHomePageSidebarMapping; var gptCellHomePageSidebarMapping; var gptInterscrollerMapping; var gptLeaderboardSizeMapping; var gptMobileSizeMapping; var gptPrestitialMapping; var gptRectangleShortSizeMapping; var gptRectangleSizeMapping; var gptSideBarSizeMapping; var gptTallSizeMapping; var gptWideSizeMapping; var gptWideRectangleSizeMapping; //*********************************************** //Start Define Size mapping based on client Viewport //*********************************************** if (gpt_AdFile === 'PU') { gptTallSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[300, 600], [160, 600], [120, 600]]). addSize([0, 0], []). build(); gptRectangleSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[300, 250]]). addSize([0, 0], []). build(); gptRectangleShortSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[300, 250], [320, 50], [300, 50]]). addSize([0, 0], [[300, 250], [320, 50], [300, 50]]). build(); gptWideSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[728, 90]]). addSize([760, 0], [[728, 90], [320, 50], [300, 50]]). addSize([0, 0], [[320, 50], [300, 50]]). build(); gptWideRectangleSizeMapping = googletag.sizeMapping(). addSize([992, 0], []). addSize([760, 0], [[320, 50], [300, 50], [300, 250]]). addSize([0, 0], [[320, 50], [300, 50], [300, 250]]). build(); gptMobileSizeMapping = googletag.sizeMapping(). addSize([0, 0], [[320, 50], [300, 50]]). build(); gptFluidMapping = googletag.sizeMapping(). addSize([0, 0], ['fluid']). build(); gptPrestitialMapping = googletag.sizeMapping(). addSize([760, 0], [[1, 1]]). build(); } else { //JBS-CELL-LANCET gptLeaderboardSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[728, 90]]). // Desktop addSize([768, 0], [[728, 90]]). // Tablet Landscape addSize([0, 0], [[320, 50], [300, 50]]). // Phone & Tablet Portrait build(); gptHomePageSidebarMapping = googletag.sizeMapping(). addSize([2090, 795], [[300, 600], [300, 250], [160, 600], [120, 600]]). addSize([1910, 795], [[160, 600], [120, 600]]). addSize([0, 0], []). build(); gptCellHomePageSidebarMapping = googletag.sizeMapping(). addSize([2090, 795], [[300, 600], [300, 250], [336, 280], [160, 600], [120, 600]]). addSize([1910, 795], [[160, 600], [120, 600]]). addSize([0, 0], []). build(); gptSideBarSizeMapping = googletag.sizeMapping(). addSize([1140, 795], [[300, 600], [160, 600], [120, 600], [300, 250]]). // SkyScraper - Desktop (Require min 630 vertical) addSize([1140, 445], [[300, 250]]). // BoomBox Fall Back - Desktop (Require min 280 vertical) addSize([0, 0], []). // Phone build(); gptBoomBoxSizeMapping = googletag.sizeMapping(). addSize([768, 0], [[300, 250], [336, 280]]). // Desktop & Tablet Landscape addSize([0, 0], []). // Phone build(); gptFluidMapping = googletag.sizeMapping(). addSize([0, 0], ['fluid']). build(); gptPrestitialMapping = googletag.sizeMapping(). addSize([600, 700], [[1, 1]]). // Desktop & Tablet Landscape addSize([0, 0], []). // Phone build(); gptInterscrollerMapping = googletag.sizeMapping(). addSize([1140, 445], []). addSize([1024, 768], [[1024, 768]]). addSize([768, 1024], [[768, 1024]]). addSize([480, 320], [[480, 320]]). addSize([320, 480], [[320, 480]]). build(); } //*********************************************** //End Define Size mapping based on client Viewport //*********************************************** //*********************************************** //Start detection for ad slots on page //*********************************************** var gptMasterPage = gpt_CheckForNULL($('#gptPage').val()); var gptMasterSite; if (gpt_AdFile === 'PU') { gptMasterSite = $('#gptSite').val(); } else { //JBS-CELL-LANCET gptMasterSite = "dev"; if (gpt_IsProd) { gptMasterSite = gpt_CheckForNULL($('#gptSite').val()); //If there is no master site, check for a defaultsite if (gptMasterSite == null) { gptMasterSite = gpt_CheckForNULL($('#gptDefaultSite').val()); } } else { //Dev ENV //If the page has no gptSite Value, assume no value which will disable ads if (gpt_CheckForNULL($('#gptSite').val()) === null) { gptMasterSite = null; } } //If there is no master Page, check for a Page using the URL if (gptMasterPage === null) { gptMasterPage = GPT_GetPageByURL(); } } $(".gpt-ad").each(function (index) { var gptPage = ''; var adSizeMapping = ''; var gptPOS; var gptTC; var gptNative; var adId; var gptSite; var tempSlot = null; if (gpt_IsProd) { //Check if the ad slot has it's own site defined if (typeof $(this).data('site') === 'undefined') { gptSite = gptMasterSite; } else { gptSite = gpt_CheckForNULL($(this).data('site')); } } else { gptSite = gptMasterSite; } if (gpt_AdFile === 'PU') { adId = $(this).attr('id'); } else { //JBS-CELL-LANCET adId = 'gpt-ad-' + index + 1; } if (gpt_CheckForNULL(gptSite) !== null) { gptSite_Debug = gptSite; gptPOS = parseInt($(this).data('pos')) || -1; if (gptPOS === -1) { gptPOS = index + 1; } //Check if the ad slot has it's own page defined gptPage = $(this).data('page'); if (gpt_CheckForNULL(gptPage) == null) { //Use the Master Page gptPage = gptMasterPage; } //If the page is not null, preceed it with a slash if (gptPage !== null) { gptPage = '/' + gptPage; } else { gptPage = ''; } gptPage_Debug = gptPage; gptTC = $(this).data('tc'); if (typeof gptTC === "undefined") { gptTC = ''; } gptNative = $(this).data('native'); if (typeof gptNative === "undefined") { gptNative = ''; } //Determine sizemapping based on data-adsize if (gpt_AdFile === 'PU') { switch ($(this).data('adsize')) { case 'tall': adSizeMapping = gptTallSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[120, 600], [160, 600], [300, 600]], adId); break; case 'rectangle': adSizeMapping = gptRectangleSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250]], adId); break; case 'rectangleshort': adSizeMapping = gptRectangleShortSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250], [320, 50], [300, 50]], adId); break; case 'wide': adSizeMapping = gptWideSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[728, 90], [320, 50], [300, 50]], adId); break; case 'widerectangle': adSizeMapping = gptWideRectangleSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[320, 50], [300, 50], [300, 250]], adId); break; case 'mobile': adSizeMapping = gptMobileSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[320, 50], [300, 50]], adId); break; case 'fluid': adSizeMapping = gptFluidMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, 'fluid', adId); break; case 'prestitial': adSizeMapping = gptPrestitialMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[1, 1]], adId); break; } } else { //JBS-CELL-LANCET switch ($(this).data('adsize')) { case 'cell-leaderboard': case 'leaderboard': adSizeMapping = gptLeaderboardSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[728, 90], [320, 50], [300, 50]], adId); break; case 'bottom': if (gpt_ResponsiveHomepage) { adSizeMapping = gptHomePageSidebarMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[120, 600], [160, 600], [300, 600], [300, 250]], adId); } else { adSizeMapping = gptBoomBoxSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250]], adId); } break; case 'boombox': if (gpt_AdFile === "CELLJOURNAL" || gpt_AdFile == "CELLBUCKET") { if (gpt_ResponsiveHomepage) { adSizeMapping = gptCellHomePageSidebarMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[120, 600], [160, 600], [300, 600], [300, 250], [336, 280]], adId); } else { adSizeMapping = gptBoomBoxSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250], [336, 280]], adId); } } else { adSizeMapping = gptBoomBoxSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250]], adId); } break; case 'interscroller': adSizeMapping = gptInterscrollerMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[320, 480], [480, 320], [768, 1024], [1024, 768]], adId); break; case 'sidebar': case 'skyscraper': adSizeMapping = gptSideBarSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[120, 600], [160, 600], [300, 600], [300, 250]], adId); break; case 'native': case 'fluid': adSizeMapping = gptFluidMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, 'fluid', adId); break; case 'prestitial': adSizeMapping = gptPrestitialMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, 'fluid', adId); break; } } } //Ignore any invalid adsizes that could be on the page if (adSizeMapping !== '') { $(this).addClass('gpt-ad-defined'); if (gpt_AdFile !== 'PU') { $(this).attr('id', adId); } tempSlot.defineSizeMapping(adSizeMapping).addService(googletag.pubads()).setTargeting("pos", gptPOS); if (gptTC !== '') { tempSlot.setTargeting("tc", gptTC); } if (gptNative !== '') { tempSlot.setTargeting("native", gptNative); } gptEvent_Debug = gptEvent_Debug + $(this).data('adsize') + ' Requested<br>'; } else { gptInvalidAdSize_Debug = gptInvalidAdSize_Debug + "Invalid Size Found, Id: " + $(this).prop('id') + ', adSize: ' + $(this).data('adsize') + '<br>'; $(this).remove(); } }); if (gpt_CheckForNULL(gptInvalidAdSize_Debug) === null) { gptInvalidAdSize_Debug = "None Detected"; } //*********************************************** //End detection for ad slots on page //*********************************************** //*********************************************** //Start page level targeting //*********************************************** if (gpt_AdFile !== 'PU') { //Logged in or IP Access gpt_TargetAccessType(); //Check for Screenshot Client gpt_CheckSSC(); } //Check for DFP Test gpt_GetDFPTestId(); //Check for Additional Targeting gpt_GetAdditionalTargeting(); if (gpt_IsProd && gptContextualEnabled) { var gpt_ContextualRetry = false; //Check for Contextual Targeting if (gs_channels !== "DEFAULT") { var gpt_ContextualCategories = Array.from(gs_channels); for (var i = 0; i < gpt_ContextualCategories.length; i++) { if (gpt_ContextualCategories[i] == 'gx_retry') { gpt_ContextualRetry = true; } if (!gpt_ContextualCategories[i].startsWith("custom_")) { //Remove any tag that is not custom gpt_ContextualCategories.splice(i, 1); i--; } else { //Strip the 'custom_' from the tag gpt_ContextualCategories[i] = gpt_ContextualCategories[i].replace("custom_", "") } } if (gpt_ContextualCategories.length > 0) { googletag.pubads().setTargeting("gs_cat", gpt_ContextualCategories); } else { gpt_ContextualCategories = 'none'; } if (gpt_ContextualRetry) { gpt_ContextualCategories = "*Indexing*"; } gptContextualResult_Debug = gpt_ContextualCategories; } else { gptContextualResult_Debug = 'No segments found'; } } else { //Not Prod gptContextualResult_Debug = 'Not enabled'; var gpt_DevSite = gpt_CheckForNULL($('#gptSite').val(), "dev"); $('#gpt-Variables').append('<input type="hidden" id="gptEnvironment" value="' + gpt_DevSite + '">'); gpt_Target("Environment"); } //*********************************************** //End page level targeting //*********************************************** //Enable google dfp services if (parseInt($('#gptLazyLoading').val()) === 1) { googletag.pubads().enableLazyLoad({ fetchMarginPercent: 200, renderMarginPercent: 0, mobileScaling: 2.0 }); } else { googletag.pubads().enableSingleRequest(); } //Add Listener for RenderEnded googletag.pubads().addEventListener('slotRenderEnded', function (event) { if (!event.isEmpty) { if (typeof LocalAdLoaded === "function") { LocalAdLoaded(event); } if (gpt_ResponsiveHomepage) { if (typeof positionAd === "function") { positionAd(); } } if (event.size[0] == "480" || event.size[1] == "480") { $('.gpt-InScrollBox').css('display', 'block'); gptEvent_Debug = gptEvent_Debug + 'Interscroller ' + event.size + ' rendered: ' + gpt_GetElapsedTime() + '<br>'; } else { gptEvent_Debug = gptEvent_Debug + event.size + ' rendered: ' + gpt_GetElapsedTime() + '<br>'; } } }); if (gpt_AdFile !== 'PU') { googletag.pubads().collapseEmptyDivs(); } googletag.enableServices(); //Populate Defined Ad Slots $(".gpt-ad-defined").each(function (index) { var adId = $(this).attr('id'); googletag.cmd.push(function () { googletag.display(adId); }); }); gptStatus_Debug = 'GPT Complete'; }); } //-------------------------------------------------------------------------- function gpt_DisplayDebug() { //Clone the template and append to Body $(document.body).append($('#gpt-DebugDiv').clone()); $('#gpt-DebugDiv').remove(); //Populate the Values gpt_LoadDebugValues(); //Display and scroll to debug section $('.gpt-DebugDiv').css('display', 'block'); window.scrollTo(0, document.body.scrollHeight); } //-------------------------------------------------------------------------- function gpt_LoadDebugValues() { $('.gpt-DebugBtn').blur(); $('.gptVersion_Debug').text(gpt_Version); $('.gptAdFile_Debug').html(gpt_AdFile); $('.gptEvent_Debug').html(gptEvent_Debug); $('.gptCustomTargeting_Debug').html(gptCustomTargeting_Debug); $('.gptSite_Debug').text(gptSite_Debug); $('.gptContextualResult_Debug').text(gptContextualResult_Debug); $('.gptContextualInit_Debug').text(gptContextualInit_Debug); $('.gptContextualURL_Debug').text(gptContextualURL_Debug); $('.gptContextualReady_Debug').text(gptContextualReady_Debug); $('.gptMoatReady_Debug').text(gptMoatReady_Debug); $('.gptMoatInit_Debug').text(gptMoatInit_Debug); $('.gptTestENV_Debug').text(gptTestENV_Debug); $('.gptDisableAds_Debug').text(gptDisableAds_Debug); $('.gptStatus_Debug').text(gptStatus_Debug); $('.gptPage_Debug').text(gptPage_Debug); $('.gptInvalidAdSize_Debug').html(gptInvalidAdSize_Debug); } //-------------------------------------------------------------------------- function gpt_GrapeShotDebug() { $('.gpt-DebugBtn').blur(); window.open("http://admin-elsevier.grapeshot.co.uk/custom/bookmarklet.cgi?blocking=1&vn=2&url=" + encodeURIComponent(document.location), "GRAPESHOT_POPUP", "width=650,height=600,scrollbars=yes,screenX=40,screenY=50,menubar=no,toolbar=no,resizable=yes", "Custom").focus(); } //-------------------------------------------------------------------------- function gpt_ShowConsole() { $('.gpt-DebugBtn').blur(); googletag.openConsole(); } 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href="/products/marlin/ha/releasedAssets/css/build-article-45520a2122a8fee68553.css"/><article xmlns="http://www.w3.org/1999/xhtml" data-design="pill" data-has="right-rail" vocab="http://schema.org/" typeof="ScholarlyArticle" data-pii="S1465-3249(22)00048-2" lang="en" dir="ltr"><div data-core-wrapper="header"><header data-extent="frontmatter"><div class="core-container"><div data-article-access="no" data-article-access-type="other" class="meta-panel"><span class="meta-panel__left"><span class="meta-panel__type"><span>FULL-LENGTH ARTICLE</span><span class="subtype"> | Basic Research</span></span></span><span class="meta-panel__middle"><span class="meta-panel__volumeIssue"><a href="/issue/S1465-3249(22)X0006-6"><span>Volume 24</span>, <span>Issue 6</span></a></span><span class="meta-panel__pages"><span>p597-607</span></span><span class="meta-panel__onlineDate">June 2022</span></span><span class="meta-panel__right"></span></div><h1 property="name">Dental pulp stem cell-derived extracellular matrix: autologous tool boosting bone regeneration</h1><div class="contributors"><span class="authors"><span role="list"><span property="author" typeof="Person" role="listitem" class="corresponding-author"><a href="#au0001"><span property="givenName">Milda</span> <span property="familyName">Alksne</span></a><sup class="xref"><a href="#aff0001" property="affiliation" typeof="Organization" role="doc-noteref">1</a></sup> <a id="ead0001" href="mailto:milda.peciukaityte@gf.vu.lt" property="email" title="Send email to Milda Alksne">milda.peciukaityte@gf.vu.lt</a></span> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0002"><span property="givenName">Migle</span> <span property="familyName">Kalvaityte</span></a><sup class="xref"><a href="#aff0001" property="affiliation" typeof="Organization" role="doc-noteref">1</a></sup></span> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0003"><span property="givenName">Egidijus</span> <span property="familyName">Simoliunas</span></a><sup class="xref"><a href="#aff0001" property="affiliation" typeof="Organization" role="doc-noteref">1</a></sup></span><span data-displayed-on="all"> ∙ … </span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0004"><span property="givenName">Ieva</span> <span property="familyName">Gendviliene</span></a><sup class="xref"><a href="#aff0002" property="affiliation" typeof="Organization" role="doc-noteref">2</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0005"><span property="givenName">Povilas</span> <span property="familyName">Barasa</span></a><sup class="xref"><a href="#aff0001" property="affiliation" typeof="Organization" role="doc-noteref">1</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0006"><span property="givenName">Ieva</span> <span property="familyName">Rinkunaite</span></a><sup class="xref"><a href="#aff0001" property="affiliation" typeof="Organization" role="doc-noteref">1</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0007"><span property="givenName">Algirdas</span> <span property="familyName">Kaupinis</span></a><sup class="xref"><a href="#aff0001" property="affiliation" typeof="Organization" role="doc-noteref">1</a></sup></span></span> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0008"><span property="givenName">Dmitrij</span> <span property="familyName">Seinin</span></a><sup class="xref"><a href="#aff0003" property="affiliation" typeof="Organization" role="doc-noteref">3</a></sup></span> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0009"><span property="givenName">Vygandas</span> <span property="familyName">Rutkunas</span></a><sup class="xref"><a href="#aff0002" property="affiliation" typeof="Organization" role="doc-noteref">2</a></sup></span> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0010"><span property="givenName">Virginija</span> <span property="familyName">Bukelskiene</span></a><sup class="xref"><a href="#aff0001" property="affiliation" typeof="Organization" role="doc-noteref">1</a></sup></span><span data-displayed-on="all"> … <span><span data-action="reveal">Show more</span></span> </span><span data-displayed-on="none" data-on-display="all" aria-hidden="true"> <span data-action="hide">Show less</span></span></span></span></div><div class="core-self-citation"><div id="core-affiliations-notes"><div class="affiliations"><div property="affiliation" typeof="Organization"><span class="label">1</span><span id="aff0001" property="name">Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania</span></div><div property="affiliation" typeof="Organization"><span class="label">2</span><span id="aff0002" property="name">Institute of Odontology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania</span></div><div property="affiliation" typeof="Organization"><span class="label">3</span><span id="aff0003" property="name">National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania</span></div></div></div><div id="core-content-info"><div class="history"><div>Publication History:</div><div><span>Received June 9, 2021</span>; <span>Revised November 22, 2021</span>; <span>Accepted February 5, 2022</span>; <span>Published online March 15, 2022</span></div></div><div class="core-links"><span class="doi">DOI: <a href="https://doi.org/10.1016/j.jcyt.2022.02.002" property="sameAs" target="_blank">10.1016/j.jcyt.2022.02.002</a></span><span class="science-direct">Also available on <a href="https://www.sciencedirect.com/science/article/pii/S1465324922000482" target="_blank">ScienceDirect</a></span></div><div role="paragraph">Copyright: © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. 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id="abss0001"><h3>Background aims</h3><div id="spara005" role="paragraph">To facilitate artificial bone construct integration into a patient's body, scaffolds are enriched with different biologically active molecules. Among various scaffold decoration techniques, coating surfaces with cell-derived extracellular matrix (ECM) is a rapidly growing field of research. In this study, for the first time, this technology was applied using primary dental pulp stem cells (DPSCs) and tested for use in artificial bone tissue construction.</div></section><section id="abss0002"><h3>Methods</h3><div id="spara006" role="paragraph">Rat DPSCs were grown on three-dimensional-printed porous polylactic acid scaffolds for 7 days. After the predetermined time, samples were decellularized, and the remaining ECM detailed proteomic analysis was performed. Further, DPSC-secreated ECM impact to mesenchymal stromal cells (MSC) behaviour as well as its role in osteoregeneration induction were analysed.</div></section><section id="abss0003"><h3>Results</h3><div id="spara007" role="paragraph">It was identified that DPSC-specific ECM protein network ornamenting surface-enhanced MSC attachment, migration and proliferation and even promoted spontaneous stem cell osteogenesis. This protein network also demonstrated angiogenic properties and did not stimulate MSCs to secrete molecules associated with scaffold rejection. With regard to bone defects, DPSC-derived ECM recruited endogenous stem cells, initiating the bone self-healing process. Thus, the DPSC-secreted ECM network was able to significantly enhance artificial bone construct integration and induce successful tissue regeneration.</div></section><section id="abss0004"><h3>Conclusions</h3><div id="spara008" role="paragraph">DPSC-derived ECM can be a perfect tool for decoration of various biomaterials in the context of bone tissue engineering.</div></section></section><section id="graphical-abstract" property="abstract" typeof="Text" role="doc-abstract"><h2 property="name">Graphical abstract</h2><div id="spara009" role="paragraph"><div class="figure-wrap"><figure id="fig0005" class="graphic"><a class="icon-full-screen" href="/cms/10.1016/j.jcyt.2022.02.002/asset/f0464439-a24f-485e-a7a0-b79c0c94af55/main.assets/ga1_lrg.jpg" target="_blank" title="View full size image in a new tab"><img alt="Image, graphical abstract" src="/cms/10.1016/j.jcyt.2022.02.002/asset/9025d2c7-6fa9-4679-9286-5c65865c9690/main.assets/ga1.jpg" height="125" width="301" data-viewer-src="/cms/10.1016/j.jcyt.2022.02.002/asset/f0464439-a24f-485e-a7a0-b79c0c94af55/main.assets/ga1_lrg.jpg" loading="lazy" /></a></figure></div></div></section></div></div><div class="core-linked-content"></div><section id="keywords" property="keywords"><h2>KeyWords</h2><ol><li><a href="/action/doSearch?AllField="bone"&journalCode=jcyt" alt="Search on this keyword">bone</a></li><li><a href="/action/doSearch?AllField="bone+regeneration"&journalCode=jcyt" alt="Search on this keyword">bone regeneration</a></li><li><a href="/action/doSearch?AllField="dental+pulp+stem+cell-derived+extracellular+matrix"&journalCode=jcyt" alt="Search on this keyword">dental pulp stem cell-derived extracellular matrix</a></li><li><a href="/action/doSearch?AllField="dental+pulp+stem+cells"&journalCode=jcyt" alt="Search on this keyword">dental pulp stem cells</a></li><li><a href="/action/doSearch?AllField="extracellular+matrix"&journalCode=jcyt" alt="Search on this keyword">extracellular matrix</a></li></ol></section><div class="core-linked-content"></div><div class="core-linked-content"></div><section id="bodymatter" data-extent="bodymatter" property="articleBody" typeof="Text"><div class="core-container"><section id="articleDenialBlock" aria-labelledby="denial-block-title" class="denial-block"><div class="denial-block__left"><div class="denial-block__logo"> <span data-widget-id="6ac68c37-bc13-4db2-a8ed-03e679a8b191" data-widget-name="ux3-general-image"><a href="/action/ShowMarlinJournalHome?journalCode=jcyt" title="Cytotherapy home. 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property="affiliation" typeof="Organization"><span property="name">Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Alksne/Milda" target="_blank">Search for articles by this author</a></div></div></div><div id="au0002" property="author" typeof="Person"><div class="heading"><span property="givenName">Migle</span> <span property="familyName">Kalvaityte</span> <a class="orcid-id" href="https://orcid.org/0000-0003-3435-132X" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0003-3435-132X</a></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Kalvaityte/Migle" target="_blank">Search for articles by this author</a></div></div></div><div id="au0003" property="author" typeof="Person"><div class="heading"><span property="givenName">Egidijus</span> <span property="familyName">Simoliunas</span></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Simoliunas/Egidijus" target="_blank">Search for articles by this author</a></div></div></div><div id="au0004" property="author" typeof="Person"><div class="heading"><span property="givenName">Ieva</span> <span property="familyName">Gendviliene</span></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Institute of Odontology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Gendviliene/Ieva" target="_blank">Search for articles by this author</a></div></div></div><div id="au0005" property="author" typeof="Person"><div class="heading"><span property="givenName">Povilas</span> <span property="familyName">Barasa</span></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Barasa/Povilas" target="_blank">Search for articles by this author</a></div></div></div><div id="au0006" property="author" typeof="Person"><div class="heading"><span property="givenName">Ieva</span> <span property="familyName">Rinkunaite</span> <a class="orcid-id" href="https://orcid.org/0000-0001-9956-4022" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0001-9956-4022</a></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Rinkunaite/Ieva" target="_blank">Search for articles by this author</a></div></div></div><div id="au0007" property="author" typeof="Person"><div class="heading"><span property="givenName">Algirdas</span> <span property="familyName">Kaupinis</span> <a class="orcid-id" href="https://orcid.org/0000-0003-3157-6670" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0003-3157-6670</a></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Kaupinis/Algirdas" target="_blank">Search for articles by this author</a></div></div></div><div id="au0008" property="author" typeof="Person"><div class="heading"><span property="givenName">Dmitrij</span> <span property="familyName">Seinin</span></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Seinin/Dmitrij" target="_blank">Search for articles by this author</a></div></div></div><div id="au0009" property="author" typeof="Person"><div class="heading"><span property="givenName">Vygandas</span> <span property="familyName">Rutkunas</span></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Institute of Odontology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Rutkunas/Vygandas" target="_blank">Search for articles by this author</a></div></div></div><div id="au0010" property="author" typeof="Person"><div class="heading"><span property="givenName">Virginija</span> <span property="familyName">Bukelskiene</span></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania</span></div></div><div class="core-author-link"><a href="/authored-by/Bukelskiene/Virginija" target="_blank">Search for articles by this author</a></div></div></div></section></div><div class="core-collateral-previews"><template id="core-collateral-figures-preview"><div class="figure-wrap"><figure id="fig0001" class="graphic"><img alt="Fig 1" src="/cms/10.1016/j.jcyt.2022.02.002/asset/937197b3-d6fa-4db3-84fb-9ac916d72c92/main.assets/gr1.sml" loading="lazy" /><figcaption class="figure__caption__body"><div id="fig0001-title" class="figure__title"><span class="label figure__label">Figure 1</span> <span class="figure__title__text">PLA scaffold characteristics, decellularization process effectiveness and detailed DPSC-produced ECM analysis. (A) SEM images of the 3D-printed porous PLA scaffolds. (B) Visualized fibronectin or actin filaments (red = Alexa Fluor 594) and DNA residues (blue = DAPI). (C) DNA residue quantification after cell removal procedure by DAPI assay. Results are presented as median ± IQR. (D) Proteins grouped by their cellular localization. Results are presented as a pie chart. (E) Matrisome signature of DPSC-secreted ECM. Results are presented as a pie chart. (F) Biological processes evaluated by GO analysis. DAPI, 4′,6-diamidino-2-phenylindole; IQR, interquartile range; SEM, scanning electron microscope. (Color version of figure is available online.)</span></div></figcaption></figure></div><div class="figure-wrap"><figure id="fig0002" class="graphic"><img alt="Fig 2" src="/cms/10.1016/j.jcyt.2022.02.002/asset/a47658cb-7b20-4f6a-a45b-aeca06bc2f50/main.assets/gr2.sml" loading="lazy" /><figcaption class="figure__caption__body"><div id="fig0002-title" class="figure__title"><span class="label figure__label">Figure 2</span> <span class="figure__title__text">DPSC behavior on ECM-coated scaffolds. (A) Representative images of visualized nucleus (blue = DAPI) and FA (green = vinculin) in DPSCs. (B) Cell surface area measurement. (C) Quantification of FA spots within the cells. (D) DPSC migration onto the PLA and PLA+ECM scaffolds. (E) Cell proliferation rate. Results are standardized according to the number of cells maintained on appropriate scaffolds for 24 h. *<i>P</i> < 0.05 and ***<i>P</i> < 0.001 (indicate significant differences between tested groups). ###<i>P</i> < 0.001 (indicates significant differences compared with 0.5 h within the same scaffold group). ΔΔΔ<i>P</i> < 0.001 (indicates significant differences in data compared with 2 h within the same group). DAPI, 4′,6-diamidino-2-phenylindole; FA, focal adhesion. (Color version of figure is available online.)</span></div></figcaption></figure></div><div class="figure-wrap"><figure id="fig0003" class="graphic"><img alt="Fig 3" src="/cms/10.1016/j.jcyt.2022.02.002/asset/5e33ccc2-e6f5-4fd2-bf81-836a9ac7ed8e/main.assets/gr3.sml" loading="lazy" /><figcaption class="figure__caption__body"><div id="fig0003-title" class="figure__title"><span class="label figure__label">Figure 3</span> <span class="figure__title__text">Impact of ECM-coated scaffold on the osteogenesis and osteointegration of DPSCs <i>in vitro</i>. (A) Runx2 protein mRNA expression level in DPSCs. (B) OPN protein mRNA expression level in DPSCs. (C) ALP activity evaluation. (D) DPSC collagen production quantification. (E) ECM mineralization analysis. (F) PESC migration onto the PLA and PLA+ECM scaffolds. (G) Dot blot analysis data of bioactive molecules detected in secretomes of DPSCs grown on tested samples. *<i>P</i> < 0.05 and ***<i>P</i> < 0.001 (indicate significant differences between tested groups). ##<i>P</i> < 0.01 and ###<i>P</i> < 0.001 (indicate significant differences compared with day 1 within the same scaffold group). Δ<i>P</i> < 0.05, ΔΔ<i>P</i> < 0.01 and ΔΔΔ<i>P</i> < 0.001 (indicate significant differences compared with day 7 within the same group). (Color version of figure is available online.)</span></div></figcaption></figure></div><div class="figure-wrap"><figure id="fig0004" class="graphic"><img alt="Fig 4" src="/cms/10.1016/j.jcyt.2022.02.002/asset/030ed0b9-6c85-479b-8386-fcba322554e6/main.assets/gr4.sml" loading="lazy" /><figcaption class="figure__caption__body"><div id="fig0004-title" class="figure__title"><span class="label figure__label">Figure 4</span> <span class="figure__title__text">Bone regeneration <i>in vivo</i>. (A) Representative processed micro-CT images of volume of newly formed bone (mm<sup>3</sup>) in PLA (purple) and PLA+ECM (blue) scaffolds. (B) Box plot representing volume of newly formed bone (mm<sup>3</sup>) according to sample groups. (C) Histological section images (hematoxylin and eosin staining). Images on left represent typical findings of samples for both sexes. (D) Box plot representing histology results of the area (mm<sup>2</sup>) of newly formed bone according to sample groups. *<i>P</i> < 0.05 and ***<i>P</i> < 0.001 (indicate significant differences between tested groups). C, connective tissue; NB, new bone; S, scaffold. 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Dental pulp stem cell-derived extracellular matrix: autologous tool boosting bone regeneration - Cytotherapy