Delivery of a novel porous hybrid thermoresponsive hydrogel into the stroke infarct reduces reactive astrogliosis and promotes neural progenitor cell proliferation

Thermoresponsive chitosan/silk fibroin/PVA/PVP hydrogel loaded with BDNF promotes functional recovery after stroke | bioRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-M677548'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Thermoresponsive chitosan/silk fibroin/PVA/PVP hydrogel loaded with BDNF promotes functional recovery after stroke View ORCID Profile Mozammel H. Bhuiyan , Emma K. Gowing , Ute Zellhuber-McMillan , View ORCID Profile Simon F.R. Hinkley , View ORCID Profile M. Azam Ali , View ORCID Profile Andrew N. Clarkson doi: https://doi.org/10.1101/2025.10.20.683259 Mozammel H. Bhuiyan 1 University of Southern California; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mozammel H. Bhuiyan Emma K. Gowing 2 University of Otago; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ute Zellhuber-McMillan 3 University of Otago, New Zealand; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Simon F.R. Hinkley 4 Victoria University of Wellington, New Zealand Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Simon F.R. Hinkley M. Azam Ali 3 University of Otago, New Zealand; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for M. Azam Ali Andrew N. Clarkson 3 University of Otago, New Zealand; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Andrew N. Clarkson For correspondence: andrew.jenny.clarkson{at}gmail.com Abstract Info/History Metrics Supplementary material Preview PDF Abstract Stroke remains a leading cause of adult disability, driven in part by the formation of a non-permissive extracellular matrix environment that limits endogenous repair. Injectable biomaterials that can modulate this microenvironment while enabling localised therapeutic delivery, represent a promising strategy for post-stroke brain regeneration. Here, we report the development of a thermoresponsive hybrid hydrogel composed of chitosan, β-glycerophosphate, silk fibroin, polyvinyl alcohol and polyvinyl pyrrolidone, engineered to provide a tuneable physicochemical properties and enhanced biological functionalities for intracerebral delivery. Systemic optimisation identified a formulation (F6) that exhibited rapid gelation at physiological temperature, appropriate viscoelastic properties, a microporous architecture, and controlled biodegradation, conducive to cellular infiltration and molecular transport. In a mouse model of photothrombotic stroke, intracerebral delivery of the F6 hydrogel attenuated reactive astrogliosis and microglial activation in the peri-infarct region, while enhancing neurogenesis in the subventricular zone. Notably, incorporation of brain-derived neurotrophic factor within the hydrogel significantly improved functional recovery over 8 weeks, demonstrating the capacity of this hydrogel to act as a localised delivery platform for neuro-regenerative therapeutics. Together, this study establishes a tuneable thermoresponsive hydrogel platform that integrates structural support with controlled therapeutic delivery, highlighting its potential as a minimally invasive strategy for modulating the post-stroke microenvironment and promoting functional recovery. Competing Interest Statement The authors have declared no competing interest. Footnotes This version of the manuscript has been revised to include: 1. behavioural experiment results 2. effect of combining brain-derived neurotropic factor (BDNF) on behavioural outcome after stroke 2. long term effect of hyfrogel treatment on reactive astrogliosis, microglial activation and neurogenesis after stroke Funder Information Declared University of Otago Doctoral Scholarship Ministry of Business, Innovation and Employment, https://ror.org/02jtq1b51 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. View the discussion thread. Back to top Previous Next Posted May 26, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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Clarkson bioRxiv 2025.10.20.683259; doi: https://doi.org/10.1101/2025.10.20.683259 Share This Article: Copy Citation Tools Thermoresponsive chitosan/silk fibroin/PVA/PVP hydrogel loaded with BDNF promotes functional recovery after stroke Mozammel H. Bhuiyan , Emma K. Gowing , Ute Zellhuber-McMillan , Simon F.R. Hinkley , M. Azam Ali , Andrew N. 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