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        <title>Re-epithelialization and immune cell behaviour in an ex vivo human skin model</title>
        <author>Ana Rakita</author>
        <author>Nenad Nikolić</author>
        <author>Michael Mildner</author>
        <author>Johannes Matiasek</author>
        <author>Adelheid Elbe‐Bürger</author>
      </titleStmt>
      <publicationStmt>
        <p>Tag layer of the DHSS Meta-Tagging Project. The article text is reproduced from the
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           standOff so that overlapping and nested spans are preserved.</p>
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      <sourceDesc>
        <bibl>
          <title>Re-epithelialization and immune cell behaviour in an ex vivo human skin model</title>
          <date>2020</date>
          <publisher>Scientific Reports</publisher>
          <idno type="DOI">10.1038/s41598-019-56847-4</idno>
          
          <idno type="record">rakita2020-re-epithelialization-and-immune-ce</idno>
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          <note type="rights">cc-by</note>
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        <person xml:id="paper"><p>the paper's own words</p></person>
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    <spanGrp type="tags">
      <span xml:id="t0" type="object_of_study" ana="#object_of_study" resp="#paper">
        <label>re-epithelialization and immune cell behaviour in an ex vivo human skin wound made by suction</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t1" type="research_question" ana="#research_question" resp="#paper">
        <label>whether a human ex vivo wound can be made without disrupting the dermal compartment</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t2" type="contribution" ana="#contribution" resp="#paper">
        <label>a suction-blister wound model in which the basement membrane survives and the wound bed starts free of keratinocytes</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t3" type="claim_type" ana="#claim_type" resp="#paper">
        <label>method</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t4" type="phenomenon" ana="#phenomenon" resp="#paper">
        <label>closure of an epidermal wound by keratinocyte migration and proliferation from the wound edges</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t5" type="method" ana="#method" resp="#paper">
        <label>experiment</label>
        <term>experiment</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t6" type="mechanisms" ana="#mechanisms[0]" resp="#tagger" cert="0.95">
        <label>mechanisms</label>
        <term>EACH SEPARATION METHOD DAMAGES A DIFFERENT THING, WHICH IS WHY NONE IS GENERAL: heat harms epidermis and dermis, chemicals disturb the electrolyte equilibrium, enzymes kill components - and mechanical force is chosen because it changes nothing chemically</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t7" type="mechanisms" ana="#mechanisms[1]" resp="#tagger" cert="0.95">
        <label>mechanisms</label>
        <term>THE MODEL&#x27;S WHOLE POINT IS WHAT IT LEAVES INTACT: the basement membrane survives blister roof removal and no keratinocytes remain in the wound bed, so closure afterwards must come from the edges</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t8" type="mechanisms" ana="#mechanisms[2]" resp="#tagger" cert="0.95">
        <label>mechanisms</label>
        <term>EX VIVO IS SLOWER THAN IN VIVO AND THE PAPER SAYS WHY: culture lacks factors that arriving cells from the circulation would supply, and the dermal cells have been removed</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t9" type="limitations" ana="#limitations[0]" resp="#tagger" cert="0.95">
        <label>EVERY EXPERIMENT SHOWN USES ABDOMINAL SKIN ONLY, stated by the authors in their own discussion</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t10" type="limitations" ana="#limitations[1]" resp="#tagger" cert="0.95">
        <label>Re-epithelialization in the model is slower than in vivo, which the paper attributes to missing culture factors and to the removal of dermal cells</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t11" type="limitations" ana="#limitations[2]" resp="#tagger" cert="0.95">
        <label>The model produces a differentiation pattern NOT seen in normal skin - DSG1 and CDSN in lower epidermal layers, read as premature cornification</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t12" type="limitations" ana="#limitations[3]" resp="#tagger" cert="0.95">
        <label>No separation method is appropriate for all purposes, on the paper&#x27;s own account - so the model is offered as one technique among several rather than as a replacement</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t13" type="limitations" ana="#limitations[4]" resp="#tagger" cert="0.85">
        <label>The literature is described as large and yet lacking a standardised ex vivo model that leaves the dermal compartment undisrupted</label>
        <note>about this quote: the quote carries SMALL-CAPS RENDERED AS LOWERCASE: the paper&#x27;s “Nonetheless” opens a sentence and is staged as “nonetheless”. Verbatim against the staged text and harmless to the reading, but it is why the sentence looks like a comma splice. Confidence 0.85 under an earlier note of ours.</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t14" type="controls" ana="#controls[0]" resp="#tagger" cert="0.85">
        <label>the same suction applied to ex vivo thigh and arm skin, to show the method does not depend on the body site</label>
        <note>eliminates: that the re-epithelialization result is a property of abdominal skin, which is what was available - the paper says thigh and arm skin gave the same result and does not show it · outcome: absent-declared-unreported · would have ruled out, had it been run: the objection that the model works only on abdominal skin</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t15" type="concepts" ana="#concepts[0]" resp="#paper" cert="0.95">
        <label>negative pressure</label>
        <term>negative pressure</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t16" type="concepts" ana="#concepts[1]" resp="#paper" cert="0.95">
        <label>basement membrane</label>
        <term>basement membrane</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t17" type="concepts" ana="#concepts[2]" resp="#paper" cert="0.95">
        <label>blister roof</label>
        <term>blister roof</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t18" type="concepts" ana="#concepts[3]" resp="#paper" cert="0.95">
        <label>keratinocytes</label>
        <term>keratinocytes</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t19" type="concepts" ana="#concepts[4]" resp="#paper" cert="0.95">
        <label>re-epithelialization</label>
        <term>re-epithelialization</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t20" type="concepts" ana="#concepts[5]" resp="#paper" cert="0.95">
        <label>animal model</label>
        <term>animal model</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t21" type="concepts" ana="#concepts[6]" resp="#paper" cert="0.95">
        <label>separation technique</label>
        <term>separation technique</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t22" type="concepts" ana="#concepts[7]" resp="#paper" cert="0.95">
        <label>suction</label>
        <term>suction</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t23" type="concepts" ana="#concepts[8]" resp="#paper" cert="0.95">
        <label>epidermis</label>
        <term>epidermis</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t24" type="concepts" ana="#concepts[9]" resp="#paper" cert="0.95">
        <label>dermis</label>
        <term>dermis</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t25" type="concepts" ana="#concepts[10]" resp="#paper" cert="0.95">
        <label>abdominal skin</label>
        <term>abdominal skin</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t26" type="concepts" ana="#concepts[11]" resp="#paper" cert="0.95">
        <label>3 R principle</label>
        <term>3 R principle</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t27" type="concepts" ana="#concepts[12]" resp="#paper" cert="0.95">
        <label>cornification</label>
        <term>cornification</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t28" type="concepts" ana="#concepts[13]" resp="#paper" cert="0.95">
        <label>wound re-epithelialization</label>
        <term>wound re-epithelialization</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t29" type="concepts" ana="#concepts[14]" resp="#paper" cert="0.95">
        <label>terminal differentiation program</label>
        <term>terminal differentiation program</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t30" type="concepts" ana="#concepts[15]" resp="#paper" cert="0.95">
        <label>Hemidesmosomes</label>
        <term>Hemidesmosomes</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t31" type="concepts" ana="#concepts[16]" resp="#paper" cert="0.95">
        <label>desmosomes</label>
        <term>desmosomes</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t32" type="concepts" ana="#concepts[17]" resp="#paper" cert="0.95">
        <label>epithelial wound regeneration</label>
        <term>epithelial wound regeneration</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t33" type="concepts" ana="#concepts[18]" resp="#paper" cert="0.95">
        <label>dermal efflux</label>
        <term>dermal efflux</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t34" type="concepts" ana="#concepts[19]" resp="#paper" cert="0.95">
        <label>suction blister fluid</label>
        <term>suction blister fluid</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t35" type="concepts" ana="#concepts[20]" resp="#paper" cert="0.95">
        <label>MMP-9</label>
        <term>MMP-9</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t36" type="concepts" ana="#concepts[21]" resp="#paper" cert="0.95">
        <label>detaching basal keratinocytes</label>
        <term>detaching basal keratinocytes</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t37" type="concepts" ana="#concepts[22]" resp="#paper" cert="0.95">
        <label>wound closure</label>
        <term>wound closure</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t38" type="concepts" ana="#concepts[23]" resp="#paper" cert="0.95">
        <label>VEGF release</label>
        <term>VEGF release</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t39" type="concepts" ana="#concepts[24]" resp="#paper" cert="0.95">
        <label>angiogenesis</label>
        <term>angiogenesis</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t40" type="concepts" ana="#concepts[25]" resp="#paper" cert="0.95">
        <label>removal of dermal cells</label>
        <term>removal of dermal cells</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t41" type="concepts" ana="#concepts[26]" resp="#paper" cert="0.95">
        <label>slight delay of re-epithelialization</label>
        <term>slight delay of re-epithelialization</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t42" type="concepts" ana="#concepts[27]" resp="#paper" cert="0.95">
        <label>Topical negative pressure</label>
        <term>Topical negative pressure</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t43" type="concepts" ana="#concepts[28]" resp="#paper" cert="0.95">
        <label>ideal wound healing environment</label>
        <term>ideal wound healing environment</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t44" type="senses" ana="#senses[0]" resp="#tagger" cert="0.95">
        <label>separation technique - THE PAPER TREATS THE CHOICE AS QUESTION-DEPENDENT RATHER THAN AS A RANKING: heat, chemicals, enzymes and mechanical force each damage something different, and which damage is acceptable depends on what is being asked</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t45" type="senses" ana="#senses[1]" resp="#tagger" cert="0.95">
        <label>Re-epithelialization - epidermal regeneration completed by keratinocyte migration and differentiation</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t46" type="senses" ana="#senses[2]" resp="#tagger" cert="0.95">
        <label>wound re-epithelialization - epidermal regeneration in which keratinocytes migrate and differentiate</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t47" type="senses" ana="#senses[3]" resp="#tagger" cert="0.95">
        <label>terminal differentiation program - the differentiation transition in which basal K14/K5 are substituted by K1/K10</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t48" type="senses" ana="#senses[4]" resp="#tagger" cert="0.95">
        <label>Hemidesmosomes - basement-membrane attachments that loosen to permit keratinocyte migration</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t49" type="senses" ana="#senses[5]" resp="#tagger" cert="0.95">
        <label>desmosomes - cell-cell attachments that loosen to permit keratinocyte migration</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t50" type="senses" ana="#senses[6]" resp="#tagger" cert="0.95">
        <label>epithelial wound regeneration - the main regenerative features the ex vivo model is said to recapitulate</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t51" type="senses" ana="#senses[7]" resp="#tagger" cert="0.95">
        <label>dermal efflux - movement inferred from dermal population decreases and their appearance in blister roof/fluid</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t52" type="senses" ana="#senses[8]" resp="#tagger" cert="0.95">
        <label>suction blister fluid - one compartment in which populations absent from normal epidermis were detected</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t53" type="senses" ana="#senses[9]" resp="#tagger" cert="0.95">
        <label>MMP-9 - wound-edge factor proposed to detach basal keratinocytes and promote closure</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t54" type="senses" ana="#senses[10]" resp="#tagger" cert="0.95">
        <label>detaching basal keratinocytes - MMP-9-mediated release of basal keratinocytes from the basement membrane</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t55" type="senses" ana="#senses[11]" resp="#tagger" cert="0.95">
        <label>wound closure - the repair outcome promoted by MMP-9-linked keratinocyte detachment and migration</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t56" type="senses" ana="#senses[12]" resp="#tagger" cert="0.95">
        <label>VEGF release - release reported to be increased by MMP-9</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t57" type="senses" ana="#senses[13]" resp="#tagger" cert="0.95">
        <label>angiogenesis - vascular growth promoted by MMP-9 and dependent on endothelial MMP-9 expression</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t58" type="senses" ana="#senses[14]" resp="#tagger" cert="0.95">
        <label>removal of dermal cells - loss introduced by suction blistering that might slow re-epithelialization</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t59" type="senses" ana="#senses[15]" resp="#tagger" cert="0.95">
        <label>slight delay of re-epithelialization - the modest re-epithelialization slowdown the paper says may follow cell removal or absent incoming cells</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t60" type="senses" ana="#senses[16]" resp="#tagger" cert="0.95">
        <label>Topical negative pressure - clinical negative-pressure treatment for difficult wounds</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t61" type="senses" ana="#senses[17]" resp="#tagger" cert="0.95">
        <label>ideal wound healing environment - the local state attributed to increased flow, reduced bacterial colonization, and exudate removal</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t62" type="concept_edges" ana="#concept_edges[1]" resp="#tagger" cert="0.95">
        <label>MMP-9 —causes→ VEGF release</label>
        <term>MMP-9</term>
        <term>VEGF release</term>
        <note>the relation itself is separately evidenced · strength of the relation: 0.9 · note: The review says MMP-9 &#x27;has been reported to increase&#x27; VEGF release; weight 0.9 preserves the attribution.
Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but attributed: the span says MMP-9 &#x27;has been reported&#x27; to increase VEGF release.</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t63" type="concept_edges" ana="#concept_edges[2]" resp="#tagger" cert="0.95">
        <label>MMP-9 —causes→ angiogenesis</label>
        <term>MMP-9</term>
        <term>angiogenesis</term>
        <note>the relation itself is separately evidenced · strength of the relation: 0.9 · note: The review reports promotion and a prerequisite relation rather than presenting a new intervention; weight 0.9 preserves that status.
Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but attributed: the span says MMP-9 &#x27;has been reported&#x27; to promote angiogenesis.</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t64" type="concept_edges" ana="#concept_edges[3]" resp="#tagger" cert="0.95">
        <label>removal of dermal cells —causes→ slight delay of re-epithelialization</label>
        <term>removal of dermal cells</term>
        <term>slight delay of re-epithelialization</term>
        <note>the relation itself is separately evidenced · strength of the relation: 0.7 · note: The paper says removal and/or absent incoming cells &#x27;might cause&#x27; the delay; weight 0.7 preserves both modality and alternative causation.
Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says the removal MIGHT cause a slight delay; hedged.</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t65" type="concept_edges" ana="#concept_edges[4]" resp="#tagger" cert="0.95">
        <label>Topical negative pressure —causes→ ideal wound healing environment</label>
        <term>Topical negative pressure</term>
        <term>ideal wound healing environment</term>
        <note>the relation itself is separately evidenced · strength of the relation: 0.9 · note: The paper summarizes the clinical description of benefit through three named mechanisms; weight 0.9 marks that this is reported background rather than the paper&#x27;s experiment.
Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but attributed: the span says topical negative pressure &#x27;is described as&#x27; beneficial.</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
    </spanGrp>
  </standOff>
  <text>
    <body>
      <p><note type="rights">The full text of this article is not redistributable, so it is
      not included here. The evidence sentences are withheld with it; the tag layer and its
      grounding status remain. The article itself is at https://doi.org/10.1038/s41598-019-56847-4.</note></p>
    </body>
  </text>
</TEI>
