Re-epithelialization and immune cell behaviour in an ex vivo human skin model — TEI-tagged view

Ana Rakita, Nenad Nikolić, Michael Mildner, Johannes Matiasek, Adelheid Elbe‐Bürger · 2020 · medicine · doi:10.1038/s41598-019-56847-4 · TEI xml · tagged edition · index · concepts · authors
Where this record's text came from. 2026-08-20 and 2026-08-28 schema-0.3 passes: every quote verified as an exact substring of the staged text and anchored at merge time; concept terms verified present; every edge endpoint an existing node.
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negative pressure basement membrane blister roof keratinocytes re-epithelialization2 animal model2 separation technique suction epidermis dermis abdominal skin 3 R principle cornification wound re-epithelialization terminal differentiation program Hemidesmosomes desmosomes epithelial wound regeneration dermal efflux suction blister fluid MMP-9 detaching basal keratinocytes wound closure VEGF release angiogenesis3 removal of dermal cells slight delay of re-epithelialization Topical negative pressure ideal wound healing environment experiment113
Method, as described: negative pressure applied to ex vivo human skin, blister roof removed, cultured at an air-liquid interphase

Our tag layer for this paper

Cross-disciplinary analysis
content-tags & facets: phenomenon · claim-type · cross-domain-transfer · mechanism · claim-relation · replication-status · limitation — grounded in the full text
phenomenonclosure of an epidermal wound by keratinocyte migration and proliferation from the wound edges— “Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area.”
claim-typemethod— “To our knowledge, we have efficaciously applied for the first time negative pressure (suction) to ex vivo human skin leading to the formation of typical blisters.”
method — evidence— “Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour.”
object of study — evidence— “Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour.”
research question — evidence— “A large body of literature is available on wound healing in humans. nonetheless, a standardized ex vivo wound model without disruption of the dermal compartment has not been put forward with compelling justification.”
contribution — evidence— “Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area.”
mechanismEACH 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— “Simplicity of separation by inducing heat is accompanied by its damaging influence on both epidermis and dermis12. Chemical reagents disturb the electrolyte cellular equilibrium, or in case of enzymes, kill important components13,14.”mechanisms[0]
mechanismTHE MODEL'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— “Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area.”mechanisms[1]
mechanismEX 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— “This was somewhat delayed compared to in vivo experiments41 and may be due to a deficiency of factors under culture conditions that are produced by newly arriving cells from the circulation in vivo and/or removal of the dermal cells.”mechanisms[2]
senseseparation 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— “Simplicity of separation by inducing heat is accompanied by its damaging influence on both epidermis and dermis12. Chemical reagents disturb the electrolyte cellular equilibrium, or in case of enzymes, kill important components13,14.”senses[0]
senseRe-epithelialization - epidermal regeneration completed by keratinocyte migration and differentiation— “To fully restore epidermal barrier function, a wound requires regeneration of the epidermis through wound re-epithelialization, where keratinocytes migrate and differentiate to complete this process1. Keratin 14 (K14) and K5 expressed in mitotically active basal layer cells2,3 are substituted by K1 and K10 when entering the terminal…senses[1]
sensewound re-epithelialization - epidermal regeneration in which keratinocytes migrate and differentiate— “To fully restore epidermal barrier function, a wound requires regeneration of the epidermis through wound re-epithelialization, where keratinocytes migrate and differentiate to complete this process1. Keratin 14 (K14) and K5 expressed in mitotically active basal layer cells2,3 are substituted by K1 and K10 when entering the terminal…senses[2]
senseterminal differentiation program - the differentiation transition in which basal K14/K5 are substituted by K1/K10— “To fully restore epidermal barrier function, a wound requires regeneration of the epidermis through wound re-epithelialization, where keratinocytes migrate and differentiate to complete this process1. Keratin 14 (K14) and K5 expressed in mitotically active basal layer cells2,3 are substituted by K1 and K10 when entering the terminal…senses[3]
senseHemidesmosomes - basement-membrane attachments that loosen to permit keratinocyte migration— “To fully restore epidermal barrier function, a wound requires regeneration of the epidermis through wound re-epithelialization, where keratinocytes migrate and differentiate to complete this process1. Keratin 14 (K14) and K5 expressed in mitotically active basal layer cells2,3 are substituted by K1 and K10 when entering the terminal…senses[4]
sensedesmosomes - cell-cell attachments that loosen to permit keratinocyte migration— “To fully restore epidermal barrier function, a wound requires regeneration of the epidermis through wound re-epithelialization, where keratinocytes migrate and differentiate to complete this process1. Keratin 14 (K14) and K5…senses[5]
senseepithelial wound regeneration - the main regenerative features the ex vivo model is said to recapitulatesenses[6]
sensedermal efflux - movement inferred from dermal population decreases and their appearance in blister roof/fluid
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[7]
sensesuction blister fluid - one compartment in which populations absent from normal epidermis were detected
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[8]
senseMMP-9 - wound-edge factor proposed to detach basal keratinocytes and promote closure
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[9]
sensedetaching basal keratinocytes - MMP-9-mediated release of basal keratinocytes from the basement membrane
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[10]
sensewound closure - the repair outcome promoted by MMP-9-linked keratinocyte detachment and migration
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[11]
senseVEGF release - release reported to be increased by MMP-9
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[12]
senseangiogenesis - vascular growth promoted by MMP-9 and dependent on endothelial MMP-9 expression
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[13]
senseremoval of dermal cells - loss introduced by suction blistering that might slow re-epithelialization
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[14]
senseslight delay of re-epithelialization - the modest re-epithelialization slowdown the paper says may follow cell removal or absent incoming cells
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[15]
senseTopical negative pressure - clinical negative-pressure treatment for difficult wounds
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[16]
senseideal wound healing environment - the local state attributed to increased flow, reduced bacterial colonization, and exudate removal
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[17]
controlthe same suction applied to ex vivo thigh and arm skin, to show the method does not depend on the body site — absent-declared-unreported
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
— rules out 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
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
controls[0]
auditMMP-9 —causes→ VEGF release — Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but attributed: the span says MMP-9 'has been reported' to increase VEGF release.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[1]
noteMMP-9 —causes→ VEGF release — The review says MMP-9 'has been reported to increase' VEGF release; weight 0.9 preserves the attribution.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[1]
weightMMP-9 —causes→ VEGF release — 0.9
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[1]
auditMMP-9 —causes→ angiogenesis — Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but attributed: the span says MMP-9 'has been reported' to promote angiogenesis.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[2]
noteMMP-9 —causes→ angiogenesis — The review reports promotion and a prerequisite relation rather than presenting a new intervention; weight 0.9 preserves that status.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[2]
weightMMP-9 —causes→ angiogenesis — 0.9
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[2]
auditremoval of dermal cells —causes→ slight delay of re-epithelialization — Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says the removal MIGHT cause a slight delay; hedged.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[3]
noteremoval of dermal cells —causes→ slight delay of re-epithelialization — The paper says removal and/or absent incoming cells 'might cause' the delay; weight 0.7 preserves both modality and alternative causation.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[3]
weightremoval of dermal cells —causes→ slight delay of re-epithelialization — 0.7
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[3]
auditTopical negative pressure —causes→ ideal wound healing environment — Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but attributed: the span says topical negative pressure 'is described as' beneficial.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[4]
noteTopical negative pressure —causes→ ideal wound healing environment — 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's experiment.
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concept_edges[4]
weightTopical negative pressure —causes→ ideal wound healing environment — 0.9
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concept_edges[4]
outcomecontrol — absent-declared-unreported
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controls[0]
evidence status notelimitation — the quote carries SMALL-CAPS RENDERED AS LOWERCASE: the paper'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.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[4]
limitationEVERY EXPERIMENT SHOWN USES ABDOMINAL SKIN ONLY, stated by the authors in their own discussion
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limitations[0]
limitationRe-epithelialization in the model is slower than in vivo, which the paper attributes to missing culture factors and to the removal of dermal cells
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[1]
limitationThe model produces a differentiation pattern NOT seen in normal skin - DSG1 and CDSN in lower epidermal layers, read as premature cornification
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[2]
limitationNo separation method is appropriate for all purposes, on the paper's own account - so the model is offered as one technique among several rather than as a replacement
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[3]
limitationThe literature is described as large and yet lacking a standardised ex vivo model that leaves the dermal compartment undisrupted
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[4]
Concepts
terms this paper carries, each with the sentence it was cut from — the layer that joins one paper to another. Terms with no quote yet are on CONCEPTS.html.
conceptnegative pressure
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[0]
conceptbasement membrane
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[1]
conceptblister roof
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[2]
conceptkeratinocytes
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[3]
conceptre-epithelialization
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[4]
conceptanimal model
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[5]
conceptseparation technique
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[6]
conceptsuction
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[7]
conceptepidermis
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[8]
conceptdermis
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[9]
conceptabdominal skin
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[10]
concept3 R principle
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[11]
conceptcornification
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[12]
conceptwound re-epithelialization — not defined in this paper's own words; epidermal regeneration in which keratinocytes migrate and differentiate
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[13]
conceptterminal differentiation program — not defined in this paper's own words; the differentiation transition in which basal K14/K5 are substituted by K1/K10
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[14]
conceptHemidesmosomes — not defined in this paper's own words; basement-membrane attachments that loosen to permit keratinocyte migration
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[15]
conceptdesmosomes — not defined in this paper's own words; cell-cell attachments that loosen to permit keratinocyte migration
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[16]
conceptepithelial wound regeneration — not defined in this paper's own words; the main regenerative features the ex vivo model is said to recapitulate
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[17]
conceptdermal efflux — not defined in this paper's own words; movement inferred from dermal population decreases and their appearance in blister roof/fluid
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[18]
conceptsuction blister fluid — not defined in this paper's own words; one compartment in which populations absent from normal epidermis were detected
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[19]
conceptMMP-9 — not defined in this paper's own words; wound-edge factor proposed to detach basal keratinocytes and promote closure
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[20]
conceptdetaching basal keratinocytes — not defined in this paper's own words; MMP-9-mediated release of basal keratinocytes from the basement membrane
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[21]
conceptwound closure — not defined in this paper's own words; the repair outcome promoted by MMP-9-linked keratinocyte detachment and migration
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[22]
conceptVEGF release — not defined in this paper's own words; release reported to be increased by MMP-9
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[23]
conceptangiogenesis — not defined in this paper's own words; vascular growth promoted by MMP-9 and dependent on endothelial MMP-9 expression
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[24]
conceptremoval of dermal cells — not defined in this paper's own words; loss introduced by suction blistering that might slow re-epithelialization
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[25]
conceptslight delay of re-epithelialization — not defined in this paper's own words; the modest re-epithelialization slowdown the paper says may follow cell removal or absent incoming cells
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[26]
conceptTopical negative pressure — not defined in this paper's own words; clinical negative-pressure treatment for difficult wounds
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[27]
conceptideal wound healing environment — not defined in this paper's own words; the local state attributed to increased flow, reduced bacterial colonization, and exudate removal
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[28]

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