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A 3D in vitro co-culture model for evaluating biomaterial-mediated modulation of foreign-body responses

Cakmak, Betul; Saglam-Metiner, Pelin; Beceren, Goze; Zhang, Yu S.; Yesil-Celiktas, Ozlem


DataCite XML

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/261509</identifier>
  <creators>
    <creator>
      <creatorName>Cakmak, Betul</creatorName>
      <givenName>Betul</givenName>
      <familyName>Cakmak</familyName>
      <affiliation>Ege Univ, Dept Bioengn, Fac Engn, TR-35100 Izmir, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Saglam-Metiner, Pelin</creatorName>
      <givenName>Pelin</givenName>
      <familyName>Saglam-Metiner</familyName>
      <affiliation>Ege Univ, Dept Bioengn, Fac Engn, TR-35100 Izmir, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Beceren, Goze</creatorName>
      <givenName>Goze</givenName>
      <familyName>Beceren</familyName>
      <affiliation>Ege Univ, Dept Bioengn, Fac Engn, TR-35100 Izmir, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Zhang, Yu S.</creatorName>
      <givenName>Yu S.</givenName>
      <familyName>Zhang</familyName>
      <affiliation>Harvard Med Sch, Div Engn Med, Brigham &amp; Womens Hosp, Dept Med, Cambridge, MA USA</affiliation>
    </creator>
    <creator>
      <creatorName>Yesil-Celiktas, Ozlem</creatorName>
      <givenName>Ozlem</givenName>
      <familyName>Yesil-Celiktas</familyName>
      <affiliation>Ege Univ, Dept Bioengn, Fac Engn, TR-35100 Izmir, Turkey</affiliation>
    </creator>
  </creators>
  <titles>
    <title>A 3D In Vitro Co-Culture Model For Evaluating Biomaterial-Mediated Modulation Of Foreign-Body Responses</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2022</publicationYear>
  <dates>
    <date dateType="Issued">2022-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/261509</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1007/s42242-022-00198-z</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">The immune response after implantation of a biomaterial may shorten the functional life of the implant, depending on the degree of the response. In this study, we used a polyacrylamide-alginate (PAAm-Alg) hydrogel, which has been previously characterized as a biocompatible material and shown to enhance regeneration of cartilage in vivo, along with a graphite-enhanced hydrogel (PAAm-Alg-G) as a non-biocompatible counterpart, to evaluate macrophage attachment and polarization to pro- or anti-inflammatory phenotypes. The performance of each biomaterial in the presence of fibroblasts and chondrocytes was validated by an in vitro model which demonstrated modulation of the foreign-body response. A blend of 5% gelatin methacryloyl and 0.1% methacrylated hyaluronic acid was optimized to mimic the extracellular matrix (ECM) and support cell viability, proliferation, migration, and functionality at an initial concentration of 3.25 x 10(5) cells/mL. The PAAm-Alg-G hydrogel localized in the simulated ECM showed cytotoxic and genotoxic effects for both fibroblasts and chondrocytes, while exhibiting a proliferative effect on macrophages with elevated immune response. The M1/M2 ratio was 0.73 for PAAm-Alg hydrogel but 2.64 for PAAm-Alg-G, leading to significant M1 dominance (p &amp;lt; 0.0001), as expected, on day 13. Moreover, loading PAAm-Alg hydrogel with transforming growth factor beta-3 (TGF-beta 3) resulted in a slightly more balanced M1/M2 ratio of 0.87 (p &amp;gt; 0.05). The interleukin-6 (IL-6) concentration secreted in the presence of PAAm-Alg hydrogel (4.58 pg/mL) significantly decreased (p &amp;lt; 0.0001) on day 13, while the increase (p &amp;lt; 0.0001) in interleukin-10 (IL-10) concentration (120.73 pg/mL) confirmed the switch from a pro-inflammatory to an anti-inflammatory response. Predicting immune responses by developing a simplistic yet powerful three-dimensional in vitro model provides advantages in preparing for clinical use of biomaterials.</description>
  </descriptions>
</resource>
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