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This study examines whether complex coacervates formed from oppositely charged polyelectrolytes can improve cytocompatibility. Primary amines on polyallylamine hydrochloride were quaternized to yield q-pAH, then combined with negatively charged pSPMA to form complex coacervates. A549 cell assays (Live/Dead, MTS, LDH) and porcine tissue adhesion tests were used. Quaternization lowered the coacervate critical salt concentration and enhanced q-pAH/pSPMA cytocompatibility, though it did not eliminate intrinsic polycation cytotoxicity. Complexation with pSPMA reduced cytotoxicity via charge neutralization, while improved biocompatibility after direct cell contact was observed beyond salt-level effects.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/complex-coacervate-tissue-adhesives-effect-of-polycation-chemistry-and-ionic-strength-on-cytocompatibility/459587/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/complex-coacervate-tissue-adhesives-effect-of-polycation-chemistry-and-ionic-strength-on-cytocompatibility/459587.png","ImageObject",300,407,{"name":92,"@type":93},"WPS_1786070896","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are current tissue adhesives often unsuitable for medical use?","Question",{"text":112,"@type":113},"They can be associated with cytotoxicity, inflammation, and necrosis, motivating the need for more biocompatible alternatives.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were the coacervates formulated in this study?",{"text":117,"@type":113},"Primary amines on polyallylamine hydrochloride were quaternized to produce q-pAH, then combined with negatively charged polysulfopropyl methacrylate (pSPMA) to form complex coacervates.",{"name":119,"@type":110,"acceptedAnswer":120},"Which experiments were used to evaluate cytocompatibility and adhesion?",{"text":121,"@type":113},"A549 cell tests included Live/Dead, MTS, and LDH assays, and adhesion was additionally evaluated on porcine tissues.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},459587,1792184623,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36,"preview_page_count":4},549768072016,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Journal of Materials Science: Materials in Medicine (2026)37:11  \n[https://doi.org/10.1007/s10856-025-06994-0](https://doi.org/10.1007/s10856-025-06994-0)  \nBIOCOMPATIBILITY STUDIES  \nOriginal Research  \nComplex coacervate tissue adhesives: effect of polycation chemistry and ionic strength on cytocompatibility  \nAyla N. Kwant 1,2,3,4 ● Julien S. Es Sayed2,5 ● Peter Dijkstra2 ● Janette K. Burgess3,4 ● Dirk-Jan Slebos1,4 ● Marleen Kamperman2 ● Simon D. Pouwels 1,3,4  \nReceived: 12 June 2025 / Accepted: 10 December 2025 © The Author(s) 2025  \nAbstract  \nTissue adhesives are regularly used for wound healing, bleeding control and sealing internal organ leakages. However, currently available tissue adhesives are often cytotoxic. Polycations containing primary amines are generally known to induce cytotoxicity. Complex coacervates, composed of oppositely charged polyelectrolytes, may offer a biocompatible alternative. In this study, primary amines of polyallylamine hydrochloride (pAH) were reacted with glycidyltrimethylammonium chloride (GTMAC) following an epoxide ring nucleophilic substitution to obtain pAH with quaternary ammonium pendant groups (q-pAH) . These polycations were combined with negatively charged polysulfopropyl methacrylate (pSPMA) to form complex coacervates. The biocompatibility of the individual polyelectrolytes and resulting complex coacervates was studied using A549 cells through Live/Dead, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) and LDH (lactate dehydrogenase) assays. Additionally, adhesion to porcine tissues was evaluated. Quaternization of pAH strongly reduced the critical salt concentration (CSC) of the coacervate system, while remaining easy to process and injectable. The cytocompatibility of q-pAH/pSPMA was increased compared to pAH/pSPMA, mainly caused by the reduction of the required salt concentration. Nevertheless, quaternization did not reduce the cytotoxicity of the polycation itself. Complexation with pSPMA effectively reduced cytotoxicity through charge neutralization. Upon direct contact of A549 cells with q-pAH/pSPMA coacervates improved biocompatibility was observed compared to pAH/pSPMA, which could not be fully attributed to effects of reduced salt levels. Both coacervates formed stable, gel-like patches upon the salt switch and these adhered to various tissues. Reduction of complex coacervate cytotoxicity by polycation quaternization can be included in future designs of medical adhesives.  \n* Simon D. Pouwels[s.d.pouwels@umcg.nl](s.d.pouwels@umcg.nl)  \n1 University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, The Netherlands  \n2 University of Groningen, Polymer Science, Zernike Institute for Advanced Materials (ZIAM), Groningen, The Netherlands  \n3 University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands  \n4 University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands  \n5 Biotechnology Centre, The Silesian University of Technology, Gliwice, Poland  \nGraphical Abstract  \n1 Introduction  \nCurrent synthetic tissue adhesives, such as cyanoacrylates and polyurethanes, are widely used for medical purposes. Applications include wound healing, tissue sealing, and embolization, often offering a minimally invasive treatment [1 , 2] . However, while strong and effective, these adhesives are also associated with cytotoxicity, inﬂammation, and necrosis [3 , 4] . Therefore, there is a need for more biocompatible tissue adhesives, especially for internal usage.  \nComplex coacervates are an emerging class of adhesives. Sandcastle worms (Phragmatopoma californica) glue sand grains and pieces of shell together with complex coacervates to form underwater tube reefs [5] . Complex coacervates are formed by mixing two oppositely charged polyelectrolytes in a","cbCainsStqSAPL5n","https://ap.wps.com/l/cbCainsStqSAPL5n","pdf",3535923,16,"English","# Abstract\n# Introduction\n## Background on tissue adhesives\n## Complex coacervates and salt-switch behavior\n## Biocompatibility requirements and polycation toxicity","[{\"question\":\"Why are current tissue adhesives often unsuitable for medical use?\",\"answer\":\"They can be associated with cytotoxicity, inflammation, and necrosis, motivating the need for more biocompatible alternatives.\"},{\"question\":\"How were the coacervates formulated in this study?\",\"answer\":\"Primary amines on polyallylamine hydrochloride were quaternized to produce q-pAH, then combined with negatively charged polysulfopropyl methacrylate (pSPMA) to form complex coacervates.\"},{\"question\":\"Which experiments were used to evaluate cytocompatibility and adhesion?\",\"answer\":\"A549 cell tests included Live/Dead, MTS, and LDH assays, and adhesion was additionally evaluated on porcine tissues.\"}]","Complex coacervate tissue adhesives - effect of polycation chemistry and ionic strength on cytocompatibility | PDF",1790756313]