Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields

Nanocellulose: Source, Structure, Production,... | F1000Research "use strict";function _typeof(t){return(_typeof="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(t){return typeof t}:function(t){return t&&"function"==typeof Symbol&&t.constructor===Symbol&&t!==Symbol.prototype?"symbol":typeof t})(t)}!function(){var t=function(){var t,e,o=[],n=window,r=n;for(;r;){try{if(r.frames.__tcfapiLocator){t=r;break}}catch(t){}if(r===n.top)break;r=r.parent}t||(!function t(){var e=n.document,o=!!n.frames.__tcfapiLocator;if(!o)if(e.body){var r=e.createElement("iframe");r.style.cssText="display:none",r.name="__tcfapiLocator",e.body.appendChild(r)}else setTimeout(t,5);return!o}(),n.__tcfapi=function(){for(var t=arguments.length,n=new Array(t),r=0;r 3&&2===parseInt(n[1],10)&&"boolean"==typeof n[3]&&(e=n[3],"function"==typeof n[2]&&n[2]("set",!0)):"ping"===n[0]?"function"==typeof n[2]&&n[2]({gdprApplies:e,cmpLoaded:!1,cmpStatus:"stub"}):o.push(n)},n.addEventListener("message",(function(t){var e="string"==typeof t.data,o={};if(e)try{o=JSON.parse(t.data)}catch(t){}else o=t.data;var n="object"===_typeof(o)&&null!==o?o.__tcfapiCall:null;n&&window.__tcfapi(n.command,n.version,(function(o,r){var a={__tcfapiReturn:{returnValue:o,success:r,callId:n.callId}};t&&t.source&&t.source.postMessage&&t.source.postMessage(e?JSON.stringify(a):a,"*")}),n.parameter)}),!1))};"undefined"!=typeof module?module.exports=t:t()}(); dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (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], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://f1000research.com/js/vendor/ckeditor/' window.reactTheme = 'research'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); (function(h,o,t,j,a,r){ h.hj=h.hj||function(){(h.hj.q=h.hj.q||[]).push(arguments)}; h._hjSettings={hjid:2318163,hjsv:6}; a=o.getElementsByTagName('head')[0]; r=o.createElement('script');r.async=1; r.src=t+h._hjSettings.hjid+j+h._hjSettings.hjsv; a.appendChild(r); })(window,document,'https://static.hotjar.com/c/hotjar-','.js?sv='); search file_upload Submit your research search menu close search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Open Data, Software and Code Guidelines (PSE) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Article Processing Charges Peer Review Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Newsroom Contact My Research Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://f1000research.com/articles/14-359" }, "headline": "Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields", "datePublished": "2025-03-31T09:27:24", "dateModified": "2025-03-31T09:27:24", "author": [ { "@type": "Person", "name": "Neveen M. Ayad Hanna" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "Nanocellulose (NC) is one of the most prominent green materials for various applications. They have received increasing attention owing to their unique properties. In this review, a brief background on cellulose, its abundance in nature, chemical structure, and properties is described. Subsequently, the structure of nanocellulose, the procedures of its production, and its characteristics are discussed. This was followed by elaborating on the recent use of nanocellulose in medical and dental fields." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-359/v1", "name": "Nanocellulose: Source, Structure, Production, Properties, and Applications..." } } ] } Home Browse Nanocellulose: Source, Structure, Production, Properties, and Applications... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Hanna NMA. Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :359 ( https://doi.org/10.12688/f1000research.162115.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Review Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] Neveen M. Ayad Hanna https://orcid.org/0000-0002-1862-2938 Neveen M. Ayad Hanna https://orcid.org/0000-0002-1862-2938 PUBLISHED 31 Mar 2025 Author details Author details Restorative Dental Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, 31441, Saudi Arabia Neveen M. Ayad Hanna Roles: Conceptualization, Data Curation, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Nanocellulose (NC) is one of the most prominent green materials for various applications. They have received increasing attention owing to their unique properties. In this review, a brief background on cellulose, its abundance in nature, chemical structure, and properties is described. Subsequently, the structure of nanocellulose, the procedures of its production, and its characteristics are discussed. This was followed by elaborating on the recent use of nanocellulose in medical and dental fields. READ ALL READ LESS Keywords Biomedical, Dental, Eco-friendly, Nanocellulose Corresponding Author(s) Neveen M. Ayad Hanna ( [email protected] ) Close Corresponding author: Neveen M. Ayad Hanna Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Hanna NMA. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Hanna NMA. Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :359 ( https://doi.org/10.12688/f1000research.162115.1 ) First published: 31 Mar 2025, 14 :359 ( https://doi.org/10.12688/f1000research.162115.1 ) Latest published: 31 Mar 2025, 14 :359 ( https://doi.org/10.12688/f1000research.162115.1 ) Introduction Environmental pollution from fossil fuel consumption has raised concerns about global warming and public health. This has prompted the development of sustainable and eco-friendly materials. In this context, cellulose shows potential owing to its ample availability from several sources. This has already significantly influenced the production of advanced materials for biomedical applications. 1 Cellulose is a fibrous linear polysaccharide that plays a crucial role in the formation of plant cell walls, which arise naturally during plant cell development and cellulose biosynthesis. In addition to plants, cellulose is found in various organisms, including marine animals, such as tunicates, certain fungi, invertebrates, algae, and specific bacterial species. 1 , 2 Source of cellulose The characteristics of cellulose can vary based on factors, such as its original source, pretreatment, and processing methods. 1 , 3 Cellulose is chemically represented by the formula C6H10O5 and is composed of repetitive anhydro glucose units (AGUs) arranged in a 4C1-chain structure. Each monomer in the chain was rotated by 180° relative to its adjacent unit. 4 Typically, cellulose fibers consist of chains with 250 to 500 repeating units. A d-glucose unit with a C4-OH group which acts as a nonreducing group is present at one end of the chain, while on the other side, there is C1-OH aldehyde group, which is considered a reducing end. Cellulose typically forms assemblies of chains rather than individual molecules. These assemblies, composed of 30–100 chains, occur naturally and are stabilized by secondary bonds, mainly van der Waals bonds, as well as inter- and intra-molecular hydrogen bonds. The basic repeating unit, cellobiose, a glucose dimer, is linked to create crystalline cellulose structures called protofibrils (elementary fibrils), which agglomerate into larger clusters in the form of microfibrils and microfibrillar bands, which eventually combine to form cellulose fibers. The microstructure of cellulose, including microfibrillar bands, microfibrils, and elementary fibrils, as well as the functional chemical groups on its surface determine the range of its applications. The lateral sizes of these structures ranges from 1.5 to 3.5 nm for protofibrils, 10 to 30 nm for microfibrils, and approximately 100 nm for microfibrillar bands. Microfibrils can extend in length from several hundred nanometers to a few micrometres. The unique characteristics of cellulose, such as hydrophilicity, insolubility, and infusibility, depend mainly on its inter- and intramolecular bonds. 5 The degree of polymerization of cellulose and the length of its polymer chains significantly influence its properties. Cellulose fibrils consist of two distinct regions, crystalline and amorphous. The level of crystallinity typically ranges between 40% and 70%, depending on the cellulose source and extraction method. The crystalline arrangement of cellulose is stabilized by hydrogen bonds, 3 whereas its surface, which is rich in primary and secondary hydroxyl groups, provides high chemical functionality. This makes cellulose easily adaptable to modification with biopolymers, enabling the production of cellulose derivatives or grafting onto various materials. Hydroxyl groups interact electrostatically through hydrogen bonding, promoting the formation of an ordered structure. These hydrogen bonds play a crucial role in binder applications by facilitating the adhesion between cellulose particles and other materials. 6 Amorphous regions in cellulose are less dense and exhibit higher reactivity and lower resistance to mechanical, enzymatic, and chemical treatments than their crystalline counterparts. 5 , 7 Although cellulose has been extensively studied for many decades, nanocellulose has gained significant prominence over the past 20 years, as reflected in data from major research databases. 8 Structure and production of nanocellulose The pretreatment processes break the bonds between non-cellulosic and cellulosic components and reduce the degree of polymerization, which increases the internal surface area, reactivity, and porosity, and promotes cellulose-rich portions, followed by bleaching. 6 Nanotechnology is a key driver of innovation across industries and influences areas, such as medical applications. Nanosized materials are characterized by dimensions of approximately 100 nm or smaller, exhibiting a large surface-area-to-volume ratio, with different characteristics compared to their regular-sized counterparts. 9 The utility of cellulose is significantly enhanced when its chains aggregate to form highly ordered structures, which can then be isolated as nanoparticles, commonly referred to as cellulose nanomaterials or nanocelluloses. These materials are promising because of their unique properties. 10 In addition to being renewable and widely available, they exhibit chemical stability, exceptional stiffness, high strength, low thermal expansion coefficient, reduced density, dimensional stability, versatile surface chemistry for modifications, and nontoxic characteristics. Nanocellulose is currently produced in large quantities, owing to its wide range of applications in various fields. 11 – 21 The main categories of nanocellulose are (1) nanofibers, encompassing cellulose nanocrystals, cellulose nanofibrils, and bacterial cellulose, and (2) nanostructured materials, which include cellulose microfibrils and microcrystals. 1 , 22 , 23 These various forms can be obtained using diverse techniques and sourced from different types of cellulose materials. 11 , 12 The ability to produce nanocellulose with diverse features presents an exciting avenue for exploring underutilized biomass. The unique properties of nanocellulose at the nanoscale offer promising opportunities for various nonmedical and medical applications. 6 , 13 , 24 The growing number of publications each year underscores the increasing interest in nanomaterials. This heightened attention is further demonstrated by the development and publication of standards for cellulose nanocrystals (CNCs) by several international organizations, reflecting significant market demand. 25 The isolation of cellulose nanocrystals (CNs), one of the most widely used methods, involves hydrolyzing and esterifying cellulose in concentrated sulfuric acid for approximately two hours. The glycosidic bonds were broken by the acid, leading to a reduction in the cellulose chain length. Following this, the CNs were functionalized with sulfate groups and subsequently separated using centrifugation and dialysis. Sulfuric acid can produce highly crystalline nanocrystals with consistent nanoscale dimensions and colloidal stabilities. The crystalline domains can be isolated through mechanical processes to produce cellulose nanofibrils, whereas cellulose nanocrystals are generated using chemical treatments. Recently, cellulose nanostructures have garnered significant interest owing to their nanoscale dimensions, biodegradability, and abundance. Their remarkable properties, including stiffness, rheological behavior, flexibility, and low density, render them versatile for various applications. 26 Types of nanocellulose Cellulose nanocrystals (CNCs) As previously mentioned, hydrolysis of cellulose using sulfuric acid results in the separation of nanocrystals (CNCs), which are cylindrical elongated rod-shaped nanoparticles measuring 100–6,000 nm in length and 4–70 nm in width, with a crystallinity index ranging from 54% to 88%. 13 Previously, nanocrystalline cellulose was referred to by various names, including cellulose nanowhiskers or rod-like cellulose crystals. However, in recent years, the terminology has largely converged to terms such as nanocrystalline cellulose, cellulose nanowhiskers, and cellulose nanocrystals. 27 Cellulose nanofibrils (CNF) Cellulose nanofibrils (CNF), alternatively named nanofibrillar cellulose and nanofibrous cellulose, typically produced through mechanical processes, form an interconnected network of wider and longer nanofibers with lengths over 10,000 nm and widths ranging from 20 to 100 nm. Compared to CNCs, CNFs exhibit lower crystallinity, greater flexibility, biodegradability, superior mechanical strength, high surface area, and light weight. Cellulose nanofibrils (CNF) have been utilized as reinforcing agents in a variety of composites, including hybrid plastics, paper products, and thin packaging films. For example, the incorporation of CNF during the papermaking wet-end process enhances the strength of the resulting paper. 1 , 2 , 28 Nanocellulose for medical applications Scientific research has broadened globally to explore the applications of nanocellulose, including cellulose nanocrystals (CNCs), in various medical applications such as implants, tissue regeneration, drug delivery, and antibacterial agents. 1 , 8 , 16 , 29 Cellulose nanocrystals (CNCs) demonstrate significant potential due to their biocompatibility, non-toxic characteristics, wound-healing capabilities, high surface area-to-volume ratio, and antimicrobial characteristics. Additionally, their negative interfacial charges and abundant hydroxyl groups enable effective electrostatic adsorption onto the tissues. The key biomedical applications of CNCs include the development of antimicrobial materials, wound dressings, bone regeneration scaffolds, and drug delivery systems. 16 , 30 a. Antimicrobial materials Recently, renewable and biodegradable cellulose nanomaterials have emerged as excellent candidates for antimicrobial applications in healthcare. They are used in wound dressings because of their antimicrobial properties. Although native cellulose nanomaterials lack inherent antimicrobial properties, they can be tailored for such applications via two primary strategies. The first involves combining nanosized particles of antimicrobial agents, such as chitosan, antibiotics, silver, gold, and copper, with cellulose nanomaterials to create hybrid nanocomposites. The second strategy involves modifying the surfaces with quaternary ammonium compounds or aldehyde groups, which act as antimicrobial functional groups. Because viruses and many microbial species possess negatively charged surfaces, cellulose nanomaterials linked with quaternary groups enhance electrostatic interactions, thereby boosting antimicrobial effectiveness. 24 b. Regeneration of bone Promoting the deposition of phosphate and calcium is key for effective bone regeneration. A nanocomposite containing collagen and bacterial cellulose was developed and utilized for bone regeneration applications. This combination demonstrated excellent binding properties, making it an effective medium for joining apatite with collagen for bone repair. The study found that the bacterial cellulose-collagen-apatite nanocomposite supported the regeneration of bone without exhibiting any cytotoxic, genotoxic, or mutagenic effects. Incorporating cellulose nanocrystals into collagen-based composites has improved biocompatibility and contributes to stable mechanical performance and its ability to enhance the tensile strength of scaffolds. 31 c. Delivery of drugs Research has highlighted the potential of cellulose nanofibril (CNF) hydrogels as drug carriers owing to their unique drug release kinetics. Cellulose nanocrystals (CNC) can deliver small interfering RNAs (siRNAs) with therapeutic potential when their surface charges are modified. Naked RNA is unable to reach cancer cells effectively and is prone to rapid degradation. However, CNC, a non-toxic and biodegradable material, can bind to RNA and act as a nanocarrier, facilitating its intracellular delivery and enhancing its therapeutic efficacy. 32 d. Tissue engineering (TE), a rapidly expanding field in biomedical science, has become a leading strategy for creating biological substitutes to regenerate, treat, or repair badly affected or lost organs and tissues. This approach integrates the principles and techniques of medicine, engineering, chemistry, and biology. 20 , 33 Materials based on cellulose nanocrystals (CNCs) have gained attention in TE research because of their alignment with the key concepts of Tissue Engineering, including biocompatibility, good mechanical properties, sustainability, and ability to promote cell differentiation and growth. 21 , 34 Manufacturing tissue engineering (TE) scaffolds have been extensively researched in the past two decades, including numerous techniques such as electrospinning, 3D printing, solvent casting, and freeze-drying. 17 , 29 Cellulose nanocrystals have consistently demonstrated their potential in various TE formulations, particularly for tissue repair, especially after modifying their physical and chemical properties. In recent years, numerous formulations of biological materials loaded with cellulose nanocrystals have been developed, yielding significant results in various applications. 4 , 13 , 15 , 20 , 29 , 35 For example, Shaheen et al. created a scaffold composed of chitosan, alginate, hydroxyapatite, and cellulose nanocrystals (CNCs) for bone tissue engineering using a freeze-drying method. 36 Their findings demonstrated the enhancement of the physical and mechanical characteristics of the scaffold that included CNCs, in addition to improving cell adhesion and proliferation. It has also been found that CNC aerogels cross-linked with hydrazones are suitable as bone tissue scaffolds. 37 In addition, 3D and 4D printing has supported the development of custom bone and cartilage grafting. 38 Nanocellulose for dental applications With increasing environmental awareness, both patients and dental practitioners have shown a preference for eco-friendly alternatives. Sustainable biomaterials address this need by providing environmentally conscious choices for dental treatments and enhancing the patient experience while supporting eco-friendly dental practices instead of conventional dental materials such as amalgam fillings and non-biodegradable polymers. Their use helps to minimize waste generation and lowers the environmental impact of dental practices. Derived from renewable resources, these materials are typically biodegradable from a health standpoint, and the biocompatibility of dental materials is crucial, as it directly impacts tissue response and long-term clinical success. Cellulose-based sustainable biomaterials are recognized for their excellent biocompatibility. They promote favorable cellular interactions and tissue integration, thereby reducing the likelihood of adverse reactions and complications. These materials have led to considerable advancements in regenerative dentistry. Thus, they offer innovative possibilities for oral tissue repair and regeneration. 39 Cellulose-based biomaterials, including hydrogels, composites, and nanofibers, exhibit distinct properties that can be customized for various uses in dentistry, such as periodontal and bone regeneration. 40 Cellulose derivatives such as carboxymethylcellulose (CMC), hydroxyethyl cellulose (HEC), methylcellulose (MC), and bacterial cellulose (BC) possess distinct properties that make them suitable for specific dental applications. Owing to their enhanced mechanical properties, biocompatibility, and antibacterial activity, cellulose composites and nanomaterials including cellulose nanocrystals (CNCs) and cellulose nanofibers (CNFs) have become essential materials in dentistry. 41 Durability is a critical factor in the dental field, and nanocellulose shows promise as a reinforcing agent. A study of restorative dental materials investigated the incorporation of cellulose nanofibers (CNFs) and cellulose nanocrystals (CNCs) into a glass ionomer cement matrix to assess their effects at varying concentrations. The results showed that cellulose nanocrystals integrated seamlessly into the structure, improving the mechanical properties of the glass ionomer material and confirming its potential as an additive for tooth restoration. In contrast, the cellulose nanofibers were not effectively incorporated into the structure. 42 A study revealed that modifying flowable dental composite resins with nanocellulose significantly enhances their compressive strength. The greatest improvement (approximately 40%) was observed at 2% concentration of nanocellulose. However, increasing the concentration beyond 2% did not result in proportional gains, indicating a saturation limit. 43 Another study demonstrated a significant increase in the elastic modulus and flexural strength of polymethyl methacrylate (PMMA) denture base materials reinforced with cellulose nanocrystals and produced via injection molding. (p < 0.05). 44 A study examined the effect of incorporating nanocellulose fibers into polymethyl methacrylate (PMMA) denture base materials. The results indicated that adding cellulose nanofibers at concentrations of 0.5–1% by weight significantly improved both transverse and impact strength, with the greatest enhancement achieved at 0.5% concentration. Cellulose nanofibers also enhanced the hardness and surface roughness of the resin in a concentration-dependent manner, remaining within clinically acceptable limits without impacting other material properties. At 0.5% concentration, the translucency of the acrylic material remained unaffected, whereas a 1% concentration led to a reduction in translucency. Furthermore, cellulose nanofibers at concentrations of 0.5% and 1% significantly increased the color hue (a), whereas a 0.5% concentration notably improved the color chroma (b). Scanning electron microscopy (SEM) and Fourier-transform infrared (FTIR) analyses confirmed the effective dispersion and excellent integration of cellulose nanofibers within the acrylic resin material. 45 Another study investigated the effect of adding silica-based fillers and nanocrystalline cellulose to newly developed dental adhesives. Silica particles with a micron-sized spherical shape were synthesized using the sol-gel method, while nanocrystalline cellulose, measuring 40–80 nm in diameter, was obtained via acid hydrolysis. Fillers with higher levels of nanocrystalline cellulose (NCC) exhibit a higher degradation temperature than silica-based fillers. Moreover, they demonstrated excellent biocompatibility and enhanced proliferation of fibroblasts in vitro. Increased NCC content also resulted in significant improvements in the flexural strength, shear bond strength, Vickers hardness, and compression strength. 46 Another study showed enhanced flexural and compressive strengths in nanohybrid dental composite resin reinforced with nano-silica derived from rice husks. 47 A recent study found that incorporating 1% by weight of bacterial cellulose nanocrystals significantly enhanced the micro shear bond strength of glass ionomer cement in the dentin structure of primary teeth. Although no statistically significant difference was observed in the microleakage score of the modified glass ionomer cement, its bond strength to dentin tissue showed notable improvement. 48 In another study, cellulose nanowhiskers were integrated into gelatine-based hydrogels synthesized using the thawing-freezing method. Three concentrations of cellulose nano whiskers-1%, 2%, and 5% by weight) were evaluated to assess their impact on the solubility/degradation rate, swelling properties, and capacity for anesthetic drug loading. The hydrogels were evaluated for their potential applications in lidocaine delivery for dental procedures. The kinetics and mechanisms of lidocaine release were analyzed using established mathematical models. These loaded hydrogels show promise as raw materials for developing buccal patches, offering a potential alternative to reduce or minimize reliance on injected anesthesia during dental treatments. 49 One study focused on the development and evaluation of a novel remineralizing oral film composed of a hydroxyethylcellulose (HEC) and cellulose nanofiber (CNF) blend infused with nepheline fluorapatite glass powder. The film was assessed in vitro for its thickness, folding endurance, disintegration time, surface pH, ion release, and remineralizing effect on demineralized teeth using SEM for detailed analysis. The results indicated that the films had consistent thickness, folding endurance exceeding 300 cycles, and disintegration times lasting over 24 h. The pH values were nearly neutral and significant amounts of calcium and fluoride ions were released. SEM analysis demonstrated the uniform distribution of glass powder particles within the films. The enamel microhardness (VHN) and ultra-morphology results showed a significant increase in the mean VHN after 15 and 30 days of remineralization compared to the demineralized specimens. Thus, the newly developed films demonstrated effectiveness as a potential approach for remineralizing early demineralized tooth lesions. 50 Conclusion This short review reports the source, structure, and use of nanocellulose as the main component of different biomedical applications. It is displayed in the current review that this environmentally friendly green nanomaterial has various unique characteristics such as high surface area, good physical and mechanical characteristics, surface chemistry tailor ability, making it an outstanding material for a wide range of uses in the medical and dental fields. Ethics and consent Ethical approval and consent were not required. Data availability No data associated with this article. References 1. Trache D, Hussin MH, Haafiz MKM, et al. : Recent progress in cellulose nanocrystals: Sources and production. Nanoscale. 2017; 9 : 1763–1786. PubMed Abstract | Publisher Full Text 2. Vazquez A, Foresti M, Moran JI, et al. : Extraction and production of cellulose nanofibers. Handbook of Polymer Nanocomposites. Processing, Performance and Application. Heidelberg: Springer; 2015; 81–118. 3. Dufresne A: Nanocellulose processing properties and potential applications. Curr. For. Rep. 2019; 5 : 76–89. Publisher Full Text 4. Gopi S, Balakrishnan P, Chandradhara D, et al. : General scenarios of cellulose and its use in the biomedical field. Mater. Today Chem. 2019; 13 : 59–78. Publisher Full Text 5. Habibi Y, Lucia LA, Rojas OJ: Cellulose nanocrystals: Chemistry, self-assembly, and applications. Chem. Rev. 2010; 110 : 3479–3500. PubMed Abstract | Publisher Full Text 6. Kargarzadeh H, Ahmad I, Thomas S, et al. : Handbook of Nanocellulose and Cellulose Nanocomposites. Weinheim: John Wiley & Sons; 2017. 7. Tarchoun AF, Trache D, Klapötke TM: Microcrystalline cellulose from Posidonia oceanica brown algae: extraction and characterization. Int. J. Biol. Macromol. 2019; 138 : 837–845. PubMed Abstract | Publisher Full Text 8. Bacakova L, Pajorova J, Bacakova M, et al. : Versatile application of nanocellulose: from industry to skin tissue engineering and wound healing. Nanomaterials. 2019; 9 : 164. PubMed Abstract | Publisher Full Text | Free Full Text 9. He X, Deng H, Hwang H: The current application of nanotechnology in food and agriculture. J. Food Drug Anal. 2019; 27 : 1–21. PubMed Abstract | Publisher Full Text | Free Full Text 10. Foster EJ, Moon RJ, Agarwal UP, et al. : Current characterization methods for cellulose nanomaterials. Chem. Soc. Rev. 2018; 47 : 2609–2679. Publisher Full Text 11. Phanthong P, Reubroycharoen P, Hao X, et al. : Nanocellulose: extraction and application. Carbon Resour. Convers. 2018; 1 : 32–43. Publisher Full Text 12. Salimi S, Sotudeh-Gharebagh R, Zarghami R, et al. : Production of nanocellulose and its applications in drug delivery: a critical review. ACS Sustain. Chem. Eng. 2019; 7 : 15800–15827. Publisher Full Text 13. Naz S, Ali JS, Zia M: Nanocellulose isolation characterization and applications: a journey from non-remedial to biomedical claims. Biodesign Manuf. 2019; 2 : 187–212. Publisher Full Text 14. Moon RJ, Schueneman GT, Simonsen J: Overview of cellulose nanomaterials, their capabilities and applications.2016; 68 : 2383–2394. 15. Thomas B, Raj MC, Joy J, et al. : Nanocellulose, a versatile green platform: from biosources to materials and their applications. Chem. Rev. 2018; 118 : 11575–11625. PubMed Abstract | Publisher Full Text 16. Karimian A, Parsian H, Majidinia M, et al. : Nanocrystalline cellulose: preparation, physicochemical properties, and applications in drug delivery systems. Int. J. Biol. Macromol. 2019; 133 : 850–859. PubMed Abstract | Publisher Full Text 17. Luo H, Cha R, Li J, et al. : Advances in tissue engineering of nanocellulose-based scaffolds: a review. Carbohydr. Polym. 2019; 224 : 115144. PubMed Abstract | Publisher Full Text 18. Miao C, Hamad WY: Critical insights into the reinforcement potential of cellulose nanocrystals in polymer nanocomposites. Curr. Opin. Solid State Mater. Sci. 2019; 23 : 100761. Publisher Full Text 19. Sharma C, Bhardwaj NK: Bacterial nanocellulose: present status, biomedical applications and future perspectives. Mater. Sci. Eng. C. 2019; 104 : 109963. PubMed Abstract | Publisher Full Text 20. Shojaeiarani J, Bajwa D, Shirzadifar A: A review on cellulose nanocrystals as promising biocompounds for the synthesis of nanocomposite hydrogels. Carbohydr. Polym. 2019; 216 : 247–259. PubMed Abstract | Publisher Full Text 21. Mokhena T, John M: Cellulose nanomaterials: new generation materials for solving global issues. Cellulose. 2020; 27 : 1149–1194. Publisher Full Text 22. Hussin MH, Trache D, Chuin CTH, et al. : Extraction of cellulose nanofibers and their eco-friendly polymer composites. Sustainable Polymer Composites and Nanocomposites. Springer; 2019; pp. 653–691. 23. Pennells J, Godwin ID, Amiralian N, et al. : Trends in the production of cellulose nanofibers from non-wood sources. Cellulose. 2020; 27 : 575–593. Publisher Full Text 24. Li J, Cha R, Mou K, et al. : Nanocellulose-Based Antibacterial Materials. Adv. Healthc. Mater. 2018; 7 : 1800334. Publisher Full Text 25. Klemm D, Cranston ED, Fischer D, et al. : Nanocellulose as a natural source for groundbreaking applications in materials science: Today’s state. Mater. Today. 2018; 21 : 720–748. Publisher Full Text 26. Channab BE, Idrissi AE, Essamlali Y, et al. : Nanocellulose: Structure, modification, biodegradation and applications in agriculture as slow/controlled release fertilizer, superabsorbent, and crop protection: A review. J. Environ. Manag. 2024; 352 : 119928. PubMed Abstract | Publisher Full Text 27. Charreau H, Cavallo E, Foresti ML: Patents involving nanocellulose: analysis of their evolution since 2010. Carbohydr. Polym. 2020; 237 : 116039. PubMed Abstract | Publisher Full Text 28. Mariano M, El Kissi N, Dufresne A: Cellulose nanocrystals and related nanocomposites: review of some properties and challenges. J. Polym. Sci. Polym. Phys. 2014; 52 : 791–806. 29. Moohan J, Stewart SA, Espinosa E, et al. : Cellulose nanofibers and other biopolymers for biomedical applications. A review. Appl. Sci. 2020; 10 : 65. 30. Jorfi M, Foster EJ: Recent advances in nanocellulose for biomedical applications. J. Appl. Polym. Sci. 2015; 132 : 41719. 31. Saska S, Teixeira LN, De Castro Raucci LMS, et al. : Nanocellulose-collagen-apatite composite associated with osteogenic growth peptide for bone regeneration. Int. J. Biol. Macromol. 2017; 103 : 467–476. PubMed Abstract | Publisher Full Text 32. Ndong Ntoutoume GMA, Grassot V, Brégier F, et al. : PEI-cellulose nanocrystal hybrids as efficient siRNA delivery agents - Synthesis, physicochemical characterization and in vitro evaluation. Carbohydr. Polym. 2017; 164 : 258–267. PubMed Abstract | Publisher Full Text 33. Du H, Liu W, Zhang M, et al. : Cellulose nanocrystals and cellulose nanofibrils based hydrogels for biomedical applications. Carbohydr. Polym. 2019; 209 : 130–144. PubMed Abstract | Publisher Full Text 34. Abitbol T, Rivkin A, Cao Y, et al. : Nanocellulose, a tiny fibre with huge applications. Curr. Opin. Biotechnol. 2016; 39 : 76–88. PubMed Abstract | Publisher Full Text 35. Grishkewich N, Mohammed N, Tang J, et al. : Recent advances in the application of cellulose nanocrystals. Curr. Opin. Colloid Interface Sci. 2017; 29 : 32–45. Publisher Full Text 36. Shaheen TI, Montaser A, Li S: Effect of cellulose nanocrystals on scaffolds comprising chitosan, alginate and hydroxyapatite for bone tissue engineering. Int. J. Biol. Macromol. 2019; 121 : 814–821. PubMed Abstract | Publisher Full Text 37. Osorio DA, Lee BE, Kwiecien JM, et al. : Cross-linked cellulose nanocrystal aerogels as viable bone tissue scaffolds. Acta Biomater. 2019; 87 : 152–165. PubMed Abstract | Publisher Full Text 38. Qasim M, Chae DS, Lee NY: Advancements and frontiers in nano-based 3D and 4D scaffolds for bone and cartilage tissue engineering. Int. J. Nanomedicine. 2019; (11); 14 : 4333–4351. PubMed Abstract | Publisher Full Text | Free Full Text 39. Chojnacka K, Moustakas K, Mikulewicz M: Multifunctional cellulose-based biomaterials for dental applications: A sustainable approach to oral health and regeneration. Ind. Crop. Prod. 2023; 203 : 117142. Publisher Full Text 40. Sultan S, Mathew AP: 3D Printed Porous Cellulose Nanocomposite Hydrogel Scaffolds. J. Vis. Exp. 2019. PubMed Abstract | Publisher Full Text 41. Sabir M, Ali A, Siddiqui U, et al. : Synthesis and characterization of cellulose/hydroxyapatite based dental restorative composites. J. Biomater. Sci. Polym. Ed. 2020; 31 : 1806–1819. PubMed Abstract | Publisher Full Text 42. Silva RM, Pereira FV, Mota FAP, et al. : Dental glass ionomer cement reinforced by cellulose microfibers and cellulose nanocrystals. Mater. Sci. Eng. C. 2016; 58 : 389–395. PubMed Abstract | Publisher Full Text 43. Mohammadzadeh I, Eskandarizadeh A, Yazdanpanah M: Effect of modified nanocellulose on improving mechanical properties of flowable dental composite resin. Inorg. Chem. Commun. 2024; 161 : 112124. Publisher Full Text 44. Kawaguchi T, Lassila LVJ, Baba H, et al. : Effect of cellulose nanofiber content on flexural properties of a model, thermoplastic, injection-moulded, polymethyl methacrylate denture base material. J. Mech. Behav. Biomed. Mater. 2020; 102 : 103513. PubMed Abstract | Publisher Full Text 45. Fadhel MH, Safi IN: Evaluating the effect of the addition of Nano-cellulose fibres on certain properties of heat-cured acrylic resin denture base material. F1000Res. 2024; 13 : 529. Publisher Full Text 46. Sabir M, Muhammad N, Siddiqui U, et al. : Effect of nanocrystalline cellulose/silica-based fillers on mechanical properties of experimental dental adhesive. Polym. Bull. 2023; 80 : 9131–9148. Publisher Full Text 47. Abbas H, Alawi R, Hussin MH, et al. : Characterization of reinforced nanohybrid dental composite resin made of nano silica rice husk with the reinforcement utilizing kenaf fiber. Cellulose. 2023; 30 : 9693–9708. Publisher Full Text 48. Mohammadi N, Fattah Z, Borazjani LV: Nano-cellulose Reinforced Glass Ionomer Restorations: An in vitro study. Int. Dent. J. 2023; 73 (2): 243–250. PubMed Abstract | Publisher Full Text | Free Full Text 49. Favatela F, Horst MF, Bracone M, et al. : Gelatine/Cellulose nano whiskers hydrogels intended for the administration of drugs in dental treatments: Study of lidocaine as model case.2021. Publisher Full Text 50. Zaki D, Safwat E, Nagi S: A novel dental remineralizing blend of hydroxyethyl-cellulose and cellulose nanofibers oral film loaded with nepheline apatite glass: Preparation, characterization and in vitro evaluation of remineralizing effect. Carbohydrate Polymer Technologies and Applications. 2021; 2 : 100035. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 31 Mar 2025 ADD YOUR COMMENT Comment Author details Author details Restorative Dental Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, 31441, Saudi Arabia Neveen M. Ayad Hanna Roles: Conceptualization, Data Curation, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 31 Mar 2025, 14:359 https://doi.org/10.12688/f1000research.162115.1 Copyright © 2025 Hanna NMA. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Hanna NMA. Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :359 ( https://doi.org/10.12688/f1000research.162115.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 31 Mar 2025 Views 0 Cite How to cite this report: Sreedharan M. Reviewer Report For: Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :359 ( https://doi.org/10.5256/f1000research.178252.r375260 ) The direct URL for this report is: https://f1000research.com/articles/14-359/v1#referee-response-375260 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 16 May 2025 Mridula Sreedharan , Mahatma Gandhi University, Kottayam, Kerala, India; IRDL, Universite Bretagne Sud, Lorient, Brittany, France Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.178252.r375260 1.The topic of the review is relevant but the contents included are wide and general. The review does not report any relevant analysis, its just a report of a summary of already published works on nanocellulose. Novelty or significance of ... Continue reading READ ALL 1.The topic of the review is relevant but the contents included are wide and general. The review does not report any relevant analysis, its just a report of a summary of already published works on nanocellulose. Novelty or significance of the points explained has to be developed. 2.The conclusion part looks like a graduate level summary . Since its a short review , authors should provide suggestions, comments, current trends and future perspectives of nanocellulose in tissue engineering and dental applications should be explained. 3.Can include a graphical abstract or schematic diagram of what the authors are trying to communicate with this review which can make the review attractive. Is the topic of the review discussed comprehensively in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Tissue engineering, material engineering, biotechnology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sreedharan M. Reviewer Report For: Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :359 ( https://doi.org/10.5256/f1000research.178252.r375260 ) The direct URL for this report is: https://f1000research.com/articles/14-359/v1#referee-response-375260 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Abdelaziz KM and Khalil AA. Reviewer Report For: Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :359 ( https://doi.org/10.5256/f1000research.178252.r375258 ) The direct URL for this report is: https://f1000research.com/articles/14-359/v1#referee-response-375258 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 11 Apr 2025 Khalid M. Abdelaziz , King Khalid University, Abha, Saudi Arabia; Restorative Dental Sciences, King Khalid University, College of Dentistry, Abha, Aseer Province, Saudi Arabia Ashraf A. Khalil , Restorative Dental Sciences, King Khalid University, Abha, Aseer Province, Saudi Arabia Approved VIEWS 0 https://doi.org/10.5256/f1000research.178252.r375258 This article addressed important and updated information on a very promising biomaterial. It summarizes the chemical nature of the cellulose and the possible modification to its structure. The article shows positive outcomes of many recent studies and ... Continue reading READ ALL This article addressed important and updated information on a very promising biomaterial. It summarizes the chemical nature of the cellulose and the possible modification to its structure. The article shows positive outcomes of many recent studies and highlights the valuable applications of the cellulose-based materials specifically in both medical and dental fields. However, few typing and formatting edits are required for perfection. Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Dental Biomaterials We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Abdelaziz KM and Khalil AA. Reviewer Report For: Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :359 ( https://doi.org/10.5256/f1000research.178252.r375258 ) The direct URL for this report is: https://f1000research.com/articles/14-359/v1#referee-response-375258 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 31 Mar 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 31 Mar 25 read read Khalid M. Abdelaziz , King Khalid University, Abha, Saudi Arabia; King Khalid University, College of Dentistry, Abha, Saudi Arabia Ashraf A. Khalil , King Khalid University, Abha, Saudi Arabia Mridula Sreedharan , Mahatma Gandhi University, Kottayam, India; Universite Bretagne Sud, Lorient, France Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Sreedharan M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 May 2025 | for Version 1 Mridula Sreedharan , Mahatma Gandhi University, Kottayam, Kerala, India; IRDL, Universite Bretagne Sud, Lorient, Brittany, France 0 Views copyright © 2025 Sreedharan M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions 1.The topic of the review is relevant but the contents included are wide and general. The review does not report any relevant analysis, its just a report of a summary of already published works on nanocellulose. Novelty or significance of the points explained has to be developed. 2.The conclusion part looks like a graduate level summary . Since its a short review , authors should provide suggestions, comments, current trends and future perspectives of nanocellulose in tissue engineering and dental applications should be explained. 3.Can include a graphical abstract or schematic diagram of what the authors are trying to communicate with this review which can make the review attractive. Is the topic of the review discussed comprehensively in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? No Competing Interests No competing interests were disclosed. Reviewer Expertise Tissue engineering, material engineering, biotechnology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Sreedharan M. Peer Review Report For: Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :359 ( https://doi.org/10.5256/f1000research.178252.r375260) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-359/v1#referee-response-375260 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Abdelaziz K et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 11 Apr 2025 | for Version 1 Khalid M. Abdelaziz , King Khalid University, Abha, Saudi Arabia; Restorative Dental Sciences, King Khalid University, College of Dentistry, Abha, Aseer Province, Saudi Arabia Ashraf A. Khalil , Restorative Dental Sciences, King Khalid University, Abha, Aseer Province, Saudi Arabia 0 Views copyright © 2025 Abdelaziz K et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This article addressed important and updated information on a very promising biomaterial. It summarizes the chemical nature of the cellulose and the possible modification to its structure. The article shows positive outcomes of many recent studies and highlights the valuable applications of the cellulose-based materials specifically in both medical and dental fields. However, few typing and formatting edits are required for perfection. Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Dental Biomaterials We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Abdelaziz KM and Khalil AA. Peer Review Report For: Nanocellulose: Source, Structure, Production, Properties, and Applications in the Biomedical and Dental Fields [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :359 ( https://doi.org/10.5256/f1000research.178252.r375258) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-359/v1#referee-response-375258 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with F1000Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "Nanocellulose: Source, Structure, Production,...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://f1000research.com/articles/14-359/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://f1000research.com/articles/14-359/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://f1000research.com/articles/14-359/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Hanna NMA'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://f1000research.com/articles/14-359/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://f1000research.com/articles/14-359", templates : { twitter : "Nanocellulose: Source, Structure, Production, Properties, and.... Hanna NMA, published by " + "@F1000Research" + ", https://f1000research.com/articles/14-359/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/162115/178252") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "178252"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { "375253": 0, "375252": 0, "375255": 0, "375254": 0, "375261": 0, "375260": 4, "375257": 0, "375256": 0, "375259": 0, "375258": 16, }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "3bafc6c6-7150-4bd5-a17a-f112b3b36cb4"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); An innovative open access publishing platform offering rapid publication and open peer review, whilst supporting data deposition and sharing. Browse Gateways Collections How it Works Contact For Developers Cookie Notice Privacy Notice RSS Submit Your Research Follow us © 2012-2026 F1000 Research Ltd. ISSN 2046-1402 | Legal | Partner of Research4Life • CrossRef • ORCID • FAIRSharing R.templateTests.simpleTemplate = R.template(' $text $text $text $text $text '); R.templateTests.runTests(); var F1000platform = new F1000.Platform({ name: "f1000research", displayName: "F1000Research", hostName: "f1000research.com", id: "1", editorialEmail: "[email protected]", infoEmail: "[email protected]", usePmcStats: true }); $(function(){R.ui.dropdowns('.dropdown-for-authors, .dropdown-for-about, .dropdown-for-myresearch');}); // $(function(){R.ui.dropdowns('.dropdown-for-referees');}); $(document).ready(function () { if ($(".cookie-warning").is(":visible")) { $(".sticky").css("margin-bottom", "35px"); $(".devices").addClass("devices-and-cookie-warning"); } $(".cookie-warning .close-button").click(function (e) { $(".devices").removeClass("devices-and-cookie-warning"); $(".sticky").css("margin-bottom", "0"); }); $("#tweeter-feed .tweet-message").each(function (i, message) { var self = $(message); self.html(linkify(self.html())); }); $(".partner").on("mouseenter mouseleave", function() { $(this).find(".gray-scale, .colour").toggleClass("is-hidden"); }); }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });