1 Ocak 2023 Dergi makalesi Açık Erişim

Isik, Melis; Okesola, Babatunde O.; Eylem, Cemil Can; Kocak, Engin; Nemutlu, Emirhan; D'Este, Matteo; Mata, Alvaro; Derkus, Burak

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/271188</identifier>
  <creators>
    <creator>
      <creatorName>Isik, Melis</creatorName>
      <givenName>Melis</givenName>
      <familyName>Isik</familyName>
      <affiliation>Ankara Univ, Fac Sci, Dept Chem, Stem Cell Res Lab, TR-06560 Ankara, Turkiye</affiliation>
    </creator>
    <creator>
      <creatorName>Okesola, Babatunde O.</creatorName>
      <givenName>Babatunde O.</givenName>
      <familyName>Okesola</familyName>
      <affiliation>Univ Nottingham, Sch Life Sci, Fac Med &amp; Hlth Sci, Nottingham NG7 2UH, England</affiliation>
    </creator>
    <creator>
      <creatorName>Eylem, Cemil Can</creatorName>
      <givenName>Cemil Can</givenName>
      <familyName>Eylem</familyName>
      <affiliation>Hacettepe Univ, Fac Pharm, Analyt Chem Div, TR-06230 Ankara, Turkiye</affiliation>
    </creator>
    <creator>
      <creatorName>Kocak, Engin</creatorName>
      <givenName>Engin</givenName>
      <familyName>Kocak</familyName>
      <affiliation>Hlth Sci Univ, Fac Gulhane Pharm, Div Analyt Chem, TR-06018 Ankara, Turkiye</affiliation>
    </creator>
    <creator>
      <creatorName>Nemutlu, Emirhan</creatorName>
      <givenName>Emirhan</givenName>
      <familyName>Nemutlu</familyName>
    </creator>
    <creator>
      <creatorName>D'Este, Matteo</creatorName>
      <givenName>Matteo</givenName>
      <familyName>D'Este</familyName>
      <affiliation>AO Res Inst Davos, Clavadelerstr 8,Davos Pl, CH-7270 Davos, Switzerland</affiliation>
    </creator>
    <creator>
      <creatorName>Mata, Alvaro</creatorName>
      <givenName>Alvaro</givenName>
      <familyName>Mata</familyName>
    </creator>
    <creator>
      <creatorName>Derkus, Burak</creatorName>
      <givenName>Burak</givenName>
      <familyName>Derkus</familyName>
      <affiliation>Ankara Univ, Fac Sci, Dept Chem, Stem Cell Res Lab, TR-06560 Ankara, Turkiye</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Bioactive And Chemically Defined Hydrogels With Tunable Stiffness Guide Cerebral Organoid Formation And Modulate Multi-Omics Plasticity In Cerebral Organoids</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2023</publicationYear>
  <dates>
    <date dateType="Issued">2023-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/271188</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.actbio.2023.09.040</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;Organoids are an emerging technology with great potential in human disease modelling, drug devel-opment, diagnosis, tissue engineering, and regenerative medicine. Organoids as 3D-tissue culture sys-tems have gained special attention in the past decades due to their ability to faithfully recapitulate the complexity of organ-specific tissues. Despite considerable successes in culturing physiologically relevant organoids, their real-life applications are currently limited by challenges such as scarcity of an appropri-ate biomimetic matrix. Peptide amphiphiles (PAs) due to their well-defined chemistry, tunable bioactiv-ity, and extracellular matrix (ECM)-like nanofibrous architecture represent an attractive material scaffold for organoids development. Using cerebral organoids (COs) as exemplar, we demonstrate the possibility to create bio-instructive hydrogels with tunable stiffness ranging from 0.69 kPa to 2.24 kPa to culture and induce COs growth. We used orthogonal chemistry involving oxidative coupling and supramolec-ular interactions to create two-component hydrogels integrating the bio-instructive activity and ECM -like nanofibrous architecture of a laminin-mimetic PAs (IKVAV-PA) and tunable crosslinking density of hyaluronic acid functionalized with tyramine (HA-Try). Multi-omics technology including transcriptomics, proteomics, and metabolomics reveals the induction and growth of COs in soft HA-Tyr hydrogels contain-ing PA-IKVAV such that the COs display morphology and biomolecular signatures similar to those grown in Matrigel scaffolds. Our materials hold great promise as a safe synthetic ECM for COs induction and growth. Our approach represents a well-defined alternative to animal-derived matrices for the culture of COs and might expand the applicability of organoids in basic and clinical research. Statement of significance Synthetic bio-instructive materials which display tissue-specific functionality and nanoscale architecture of the native extracellular matrix are attractive matrices for organoids development. These synthetic ma-trices are chemically defined and animal-free compared to current gold standard matrices such as Ma-trigel. Here, we developed hydrogel matrices with tunable stiffness, which incorporate laminin-mimetic peptide amphiphiles to grow and expand cerebral organoids. Using multi-omics tools, the present study provides exciting data on the effects of neuro-inductive cues on the biomolecular profiles of brain organoids. (c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.&lt;/p&gt;</description>
  </descriptions>
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