Diversity of human skin three-dimensional organotypic cultures

Probably not a substantial claim: may not pass S3 (load-bearing).

MEK inhibition was shown as a potential targeted therapy strategy for Darier disease in a SERCA2-deficient HEE model.

“Building upon the SERCA2-deficient HEE model, Mitogen activated protein kinase kinase (MEK) inhibition was shown as a potential targeted therapy strategy for DD [30].”

• cites [30] Zaver SA, Sarkar MK, Egolf S, Zou J, Tiwaa A, Capell BC, Gudjonsson JE, Simpson CL: Targeting SERCA2 in organotypic epidermis reveals MEK inhibition as a therapeutic strategy for Darier disease. JCI Insight 2023, 8: e170739. 37561594 PMC10561730 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The HEE model is implemented in hazard assessments and regenerative medicine and is commercially available from numerous companies.

“Owing to its cost-effectiveness and reproducibility, the HEE model is also implemented in hazard assessments and regenerative medicine, where it is now commercially available from numerous companies [27,28].”

• cites [27] Hofmann E, Schwarz A, Fink J, Kamolz L-P, Kotzbeck P: Modelling the complexity of human skin in vitro. Biomedicines 2023, 11: 794. 36979772 PMC10045055 sourcePartly supported

  Section 3 (Reconstructed Human Epidermis; page not provided) says reconstructed human epidermis models are commercially available from a number of companies for hazard assessments. It does not say these models are implemented in regenerative medicine. The cited passages also do not establish cost-effectiveness as the reason for their use. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [28] Zidarič T, Kleinschek KS, Maver U, Maver T: Commercial skin equivalents. In Function-Oriented Bioengineered Skin Equivalents: Continuous Development Towards Complete Skin Replication. Edited by Zidarič T, Kleinschek KS, Maver U, Maver T Springer International Publishing; 2023: 103– 122.Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

scRNA-seq of human keratinocytes compared to holoclone signatures distinguished epidermal holoclone-forming cells from other epidermal cell states and identified a continuous hierarchical trajectory, showing that holoclone-forming cells generate meroclone- and paraclone-forming cells.

“For instance, scRNA-seq of human KCs was compared to holoclone signatures, and the resulting analyses were able to clearly distinguish epidermal holoclone-forming cells from other epidermal cell states and identify a continuous hierarchical trajectory, showing that holoclone-forming cells generate meroclone- and paraclone-forming cells [67].”

• cites [67] Enzo E, Secone Seconetti A, Forcato M, Tenedini E, Polito MP, Sala I, Carulli S, Contin R, Peano C, Tagliafico E,: Single-keratinocyte transcriptomic analyses identify different clonal types and proliferative potential mediated by FOXM1 in human epidermal stem cells. Nat Commun 2021, 12: 2505. 33947848 PMC8097075 sourceSupported

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

The versatile skin OTC-based platform is ideally suited for investigating a broad range of physiological and pathological scenarios, with significant potential for advancing understanding of skin developmental biology, disease modeling, and regenerative medicine.

“The versatile skin OTC-based platform is ideally suited for investigating a broad range of physiological and pathological scenarios, presenting significant potential for advancing our understanding of skin developmental biology, disease modeling, and applications in regenerative medicine [69–71].”

• cites [69] Cousin I, Misery L, de Vries P, Lebonvallet N: Emergence of new concepts in skin physiopathology through the use of in vitro human skin explants models. Dermatology 2023, 239: 849– 859. 37717565 sourceNot checked — no full text of the source
• cites [70] de Groot SC, Ulrich MMW, Gho CG, Huisman MA: Back to the future: from appendage development toward future human hair follicle neogenesis. Front Cell Dev Biol 2021, 9: 661787. 33912569 PMC8075059 sourcePartly supported

  The Abstract (page unavailable) discusses human models for studying hair-follicle development and disease, and their potential clinical use. The Tissue Engineering section (page unavailable) discusses regeneration, but the paper does not identify or evaluate a skin OTC-based platform as ideally suited to a broad range of physiological and pathological scenarios. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [71] Kim J, Koo B-K, Knoblich JA: Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol 2020, 21: 571– 584. 32636524 PMC7339799 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Collagen- and DED-based HSEs are increasingly recognized as promising skin models owing to their supportive cellular environments and low antigenicity.

“Significantly, collagen- and DED-based HSEs are increasingly recognized as promising skin models in skin bioengineering owing to their supportive cellular environments and low antigenicity [38,39].”

• cites [38] Zhang X, Chen X, Hong H, Hu R, Liu J, Liu C: Decellularized extracellular matrix scaffolds: recent trends and emerging strategies in tissue engineering. Bioact Mater 2022, 10: 15– 31. 34901526 PMC8637010 sourcePartly supported

  The section on dECM scaffolds for skin tissue engineering (page not provided) describes decellularized dermal scaffolds that preserve features supporting cell adhesion and growth, and reports a vascularized skin equivalent. The Conclusions and outlooks (page not provided) say removal of immunogenic cellular components reduces potential immune responses. These passages support the claim for decellularized dermal materials, but do not establish the same advantages for collagen-based HSEs or specifically say that both types are increasingly recognized as skin models. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [39] Zheng W, Xu C-H: Innovative approaches and advances for hair follicle regeneration. ACS Biomater Sci Eng 2023, 9: 2251– 2276. 37036820 sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

scRNA-seq enables profiling of gene expression at single-cell resolution and identification of reliable cellular heterogeneity, allowing identification of previously unrecognized heterogeneity, revealing regulatory relationships between genes, and tracking trajectories of distinct cell lineages.

“It enables both profiling of gene expression measurements at a single-cell resolution and identification of reliable cellular heterogeneity, allowing for the identification of previously unrecognized levels of cellular heterogeneity, revealing regulatory relationships between genes, and tracking the trajectories of distinct cell lineages in the same or different developmental stages [63–66].”

• cites [63] Glover JD, Sudderick ZR, Shih BB-J, Batho-Samblas C, Charlton L, Krause AL, Anderson C, Riddell J, Balic A, Li J,: The developmental basis of fingerprint pattern formation and variation. Cell 2023, 186: 940– 956.e20. 36764291 sourcePartly supported

  In “Single cell expression profiling delineates shared early but distinct late events,” the paper uses single-nucleus RNA-seq to characterize gene expression and identify distinct cell populations. The methods section also describes pseudotime trajectory analysis. It does not establish that this sequencing analysis revealed regulatory relationships between genes or tracked lineages across different developmental stages; the sequenced skin was from week 14. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [64]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [65] Ober-Reynolds B, Wang C, Ko JM, Rios EJ, Aasi SZ, Davis MM, Oro AE, Greenleaf WJ: Integrated single-cell chromatin and transcriptomic analyses of human scalp identify gene-regulatory programs and critical cell types for hair and skin diseases. Nat Genet 2023, 55: 1288– 1300. 37500727 PMC11190942 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites [66] Wang S, Drummond ML, Guerrero-Juarez CF, Tarapore E, MacLean AL, Stabell AR, Wu SC, Gutierrez G, That BT, Benavente CA,: Single cell transcriptomics of human epidermis identifies basal stem cell transition states. Nat Commun 2020, 11: 4239. 32843640 PMC7447770 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

The expansion of aHSEs enhances the application of OTC models for investigating therapeutic techniques, particularly in mimicking inflammatory skin diseases like psoriasis and atopic dermatitis, and in studying skin-related bacterial adhesion and infection.

“This expansion enhances the application of OTC models for investigating potential therapeutic techniques [18,60], particularly in mimicking inflammatory skin diseases like psoriasis and atopic dermatitis [59], while also studying skin-related bacterial adhesion and infection [22,45].”

• cites [18] Stanton DN, Ganguli-Indra G, Indra AK, Karande P: Bioengineered efficacy models of skin disease: advances in the last 10 years. Pharmaceutics 2022, 14: 319. 35214050 PMC8877988 sourceSupported
• cites [60] Sanchez MM, Bagdasarian IA, Darch W, Morgan JT: Organotypic cultures as aging associated disease models. Aging 2022, 14: 9338– 9383. 36435511 PMC9740367 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites [59] Scheurer J, Sauer B, Focken J, Giampetraglia M, Jäger A, Schürch CM, Weigelin B, Schittek B: Histological and functional characterization of 3D human skin models mimicking the inflammatory skin diseases psoriasis and atopic dermatitis. Dis Model Mech 2024, 17: dmm050541. 38251799 PMC10846593 sourceSupported
• cites [22]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [45] Reijnders CMA, van Lier A, Roffel S, Kramer D, Scheper RJ, Gibbs S: Development of a full-thickness human skin equivalent in vitro model derived from TERT-immortalized keratinocytes and fibroblasts. Tissue Eng Part A 2015, 21: 2448– 2459. 26135533 PMC4554934 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

aHSE models offer high customization, facilitating control over organotypic cell populations, genotypes, and culture conditions, thereby enabling controlled studies on tissue-level biology.

“aHSE models offer a high degree of customization, facilitating control over organotypic cell populations, genotypes, and culture conditions, thereby enabling meticulously controlled studies on tissue-level biology [59].”

• cites [59] Scheurer J, Sauer B, Focken J, Giampetraglia M, Jäger A, Schürch CM, Weigelin B, Schittek B: Histological and functional characterization of 3D human skin models mimicking the inflammatory skin diseases psoriasis and atopic dermatitis. Dis Model Mech 2024, 17: dmm050541. 38251799 PMC10846593 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

HSEs are used to investigate wound healing, aging, and various diseases.

“HSEs are used to investigate various aspects of normal and abnormal skin biology, including wound healing [40,41], aging [42,43], and the study of various diseases [18].”

• cites [40] Hofmann E, Fink J, Pignet A-L, Schwarz A, Schellnegger M, Nischwitz SP, Holzer-Geissler JCJ, Kamolz L-P, Kotzbeck P: Human in vitro skin models for wound healing and wound healing disorders. Biomedicines 2023, 11: 1056. 37189674 PMC10135654 sourceSupported
• cites [41] Lee E-S, Ahn Y, Bae I-H, Min D, Park NH, Jung W, Kim S-H, Hong YD, Park WS, Lee CS: Synthetic retinoid seletinoid G improves skin barrier function through wound healing and collagen realignment in human skin equivalents. Int J Mol Sci 2020, 21: 3198. 32366052 PMC7247558 sourceSupported
• cites [42] Ahlers JMD, Falckenhayn C, Holzscheck N, Solé-Boldo L, Schütz S, Wenck H, Winnefeld M, Lyko F, Grönniger E, Siracusa A: Single-cell RNA profiling of human skin reveals age-related loss of dermal sheath cells and their contribution to a juvenile phenotype. Front Genet 2022, 12: 797747. 35069694 PMC8776708 sourceSupported
• cites [43] Weinmüllner R, Zbiral B, Becirovic A, Stelzer EM, Nagelreiter F, Schosserer M, Lämmermann I, Liendl L, Lang M, Terlecki-Zaniewicz L,: Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging. NPJ Aging Mech Dis 2020, 6: 4. 32194977 PMC7060247 sourceSupported
• cites [18] Stanton DN, Ganguli-Indra G, Indra AK, Karande P: Bioengineered efficacy models of skin disease: advances in the last 10 years. Pharmaceutics 2022, 14: 319. 35214050 PMC8877988 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Although complexity increases from HEE to aHSE models, their fidelity and consistency do not necessarily improve with increasing complexity.

“Although the complexity increases from HEE to aHSE models, their fidelity and consistency do not necessarily improve with increasing complexity.”

May combine two claims.

Two-dimensional monolayer cultures cannot replicate the stratified epidermis and lack 3D cell-to-cell and extracellular matrix interactions.

“Moreover, 2D monolayer cultures are constrained by their inability to replicate the stratified epidermis and lack of 3D cell-to-cell/ECM (extracellular matrix) interactions [7].”

• cites [7] Pampaloni F, Reynaud EG, Stelzer EHK: The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol 2007, 8: 839– 845. 17684528 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The ALI-based OTC model persists as a prevalent platform used in skin development research and in mitigating limitations associated with PSC-derived skin organoid cysts.

“Despite the significant attention received by hPSC-derived skin organoids, the ALI-based OTC model persists as a prevalent platform extensively utilized not only in skin development research but also in mitigating the limitations associated with PSC-derived skin organoid cysts.”

Probably not a substantial claim: may not pass S3 (load-bearing).

RNA-seq facilitates comparison of gene expression or predicted biofunction profiles across different samples or experimental conditions.

“This capability facilitates the comparison of gene expression or predicted biofunction profiles across different samples or experimental conditions.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Single-cell RNA sequencing has become a routine method for studying human skin development.

“In the wave of technological evolution from bulk to single-cell level omics, single-cell RNA sequencing (scRNA-seq) has become a routine method for studying human skin development.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The choice of appropriate cell sources for model development holds significant potential for enhancing the reproducibility of OTCs.

“However, the choice of appropriate cell sources for model development holds significant potential for enhancing the reproducibility of OTCs.”

Probably not a substantial claim: may not pass S4 (based).

A major challenge in achieving reproducibility in skin culture systems stems from the absence of uniform, standardized protocols, which can lead to variations in culture medium, ALI duration, and key cellular parameters.

“A major challenge in achieving reproducibility in skin culture systems stems from the absence of uniform, standardized protocols, which can lead to variations in factors such as culture medium, ALI duration, and key cellular parameters (e.g. fibroblast presence, cell seeding density, passage number, etc.).”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The planar format and ample size of skin OTC models theoretically enable the adaptation and implementation of assessment approaches utilized on native human skin.

“The planar format and ample size of skin OTC models theoretically enable the adaptation and implementation of assessment approaches utilized on native human skin.”

May combine two claims.

Nagano et al. recently succeeded in generating semi-autologous skin in vivo through niche encroachment, paving the way for large-scale human skin graft production in livestock animals.

“Addressing these challenges, Nagano et al. recently succeeded in generating semi-autologous skin in vivo through niche encroachment, paving the way for large-scale human skin graft production in livestock animals [74].”

• cites [74]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S4 (based).

Skin OTC models function as a crucial intermediary between animal models, traditional 2D cell cultures, and human skin biopsies.

“Hence, skin OTC models function as a crucial intermediary between animal models, traditional 2D cell cultures, and human skin biopsies, highlighting their adaptability and versatility within the realm of skin biology.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Autologous skin grafting remains the gold standard for treating skin defects.

“Within regenerative medicine, autologous skin grafting remains the gold standard for treating skin defects.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Numerous OTC-based cultured epidermis and skin substitute products have become commercially available.

“In response to this pressing demand, numerous OTC-based cultured epidermis and skin substitute products have become commercially available (e.g. Commercially Available Skin Substitute Products [72]; Skin and Soft Tissue Substitutes [73]).”

• cites [72] Snyder D, Sullivan N, Margolis D, Schoelles K. Commercially available skin substitute products. In Skin Substitutes for Treating Chronic Wounds [Internet]. Agency for Healthcare Research and Quality (US); 2020. 32101391Not checked yet

  Not checked in the free run.

• cites [73] United Healthcare. Skin and Soft Tissue Substitutes; 2024.Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

RNA sequencing empowers researchers to simultaneously analyze the expression levels of all genes within a sample.

“Unlike low-throughput methods such as quantitative polymerase chain reaction or immunofluorescence, highly sensitive RNA sequencing (RNA-seq) empowers researchers to simultaneously analyze the expression levels of all genes within a sample.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Humanized HSEs are grafted onto immunodeficient mice as hybrid models.

“Additionally, they have been employed directly in studies and as ‘hybrid’ models, where humanized HSEs are grafted onto immunodeficient mice [44].”

• cites [44]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Using PSC-derived cells or immortalized cell lines may offer advantages over primary cell sources, which are susceptible to interdonor variability.

“For example, using PSC-derived cells or immortalized cell lines may offer advantages over primary cell sources, which are susceptible to interdonor variability.”

Classified as probably not a substantial claim.

Autologous skin grafting has clinical limitations, particularly the restricted availability of donor sites.

“However, its clinical limitations, particularly the restricted availability of donor sites, underscore the need for alternative strategies.”

May combine two claims.

Comparison of HEEs, HSEs, xenograft HEEs, and in vivo epidermis indicates that these systems resemble a fetal-like developmental state similar to PSC-based organoids and contain all the cellular states as their in vivo counterpart but may exhibit defects in basal and terminal differentiation depending on how they are cultured.

“Finally, a comparison of HEEs, HSEs, xenograft HEEs, and in vivo epidermis indicates that these systems also resemble a more fetal-like developmental state similar to the PSC-based organoids and contain all the cellular states as their in vivo counterpart but may exhibit defects in the basal and terminal differentiation programs depending on how they are cultured [44].”

• cites [44]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S4 (based).

No artificial skin substitute currently achieves full functional equivalence to autologous grafts.

“Nevertheless, no artificial skin substitute currently achieves full functional equivalence to autologous grafts.”

May combine two claims.

The two-layer design of HSEs allows optimal differentiation of the epidermis and replication of complex interactions between keratinocytes and fibroblasts, which are crucial for maintaining skin homeostasis.

“This design allows for the optimal differentiation of the epidermis and the replication of the complex interactions between KCs and Fibs, which are crucial for maintaining skin homeostasis [32].”

• cites [32] Jevtić M, Löwa A, Nováčková A, Kováčik A, Kaessmeyer S, Erdmann G, Vávrová K, Hedtrich S: Impact of intercellular crosstalk between epidermal keratinocytes and dermal fibroblasts on skin homeostasis. Biochim Biophys Acta Mol Cell Res 2020, 1867: 118722. 32302667 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based).

ALI-based planar OTC models for skin offer a robust platform enabling researchers to manipulate various types of skin cells and their microenvironments artificially.

“ALI-based planar OTC models for skin offer a robust platform enabling researchers to manipulate various types of skin cells and their microenvironments artificially.”

May combine two claims.

The produced rete ridges comprised rounded features of controlled geometry and periodicity in the dermal layer, advancing the HSE model to a more skin-like state.

“The produced rete ridges comprised rounded features of controlled geometry and periodicity in the dermal layer, advancing the current HSE model to a more skin-like state.”

• cites [62]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Large-scale personalized edgeless wearable human skin grafts vascularized by skin-specific endothelial cells resulted in enhanced ECM deposition, improved mechanical properties, and site-specific differences in cellular and ECM organization.

“Notably, the development of large-scale personalized edgeless wearable human skin grafts was further vascularized by skin-specific endothelial cells, resulting in enhanced deposition of the ECM, improved mechanical properties, and site-specific differences in cellular and ECM organization [61].”

• cites [61]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

In investigations concerning skin development, skin is frequently delineated as an intricate network of four symbiotic barriers: the physical, chemical, immune, and microbiotic layers.

“In investigations concerning skin development, skin is frequently delineated as an intricate network of four symbiotic barriers: the physical, chemical, immune, and microbiotic layers [75].”

• cites [75]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The heightened complexity of aHSEs raises the specialty required for their widespread adoption and escalates costs, particularly when utilizing cells of human origin or PSC-derived cells.

“The heightened complexity not only raises the specialty for their widespread adoption but also escalates costs, particularly when utilizing cells of human origin or PSC-derived cells.”

Probably not a substantial claim: may not pass S3 (load-bearing).

This paves the way for large-scale human skin graft production in livestock animals.

“paving the way for large-scale human skin graft production in livestock animals.”

• cites 74.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Stabell et al. conducted the first and only single-cell-based skin OTC modeling studies to date.

“Stabell and colleagues conducted the first and only single-cell-based skin OTC modeling studies to date.”

• cites 44.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

Hybrid constructs amalgamating PSC-derived skin organoids with subsequent ALI culture methods emerge as a promising foundational approach for the assembly of integrated skin systems.

“Hybrid constructs, amalgamating PSC-derived skin organoids with subsequent ALI culture methods, emerge as a promising foundational approach for the assembly of integrated skin systems.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

The advancement of in vitro skin OTC models is steadfastly trending toward enhanced complexity and functionality.

“To conclude, the advancement of in vitro skin OTC models is steadfastly trending toward enhanced complexity and functionality.”

Classified as probably not a substantial claim.

AHR and TFAP2A axis regulates terminal differentiation of epidermal keratinocytes and formation of skin barrier.

“the authors discovered a previously unrecognized axis involving AHR and TFAP2A that regulates the terminal differentiation of epidermal keratinocytes and the formation of the skin barrier.”

• cites 29.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Macrophages play a crucial role in early embryonic vascular development.

“the authors demonstrated through experiments the crucial role of macrophages in early embryonic vascular development.”

• cites 64.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

Vascularization by skin-specific endothelial cells leads to site-specific differences in cellular and ECM organization.

“the skin graft was further vascularized by skin-specific endothelial cells, leading to enhanced deposition of the ECM, improved mechanical properties, and site-specific differences in cellular and ECM organization.”

• cites 61.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Contemporary research is channeling resources into enhancing skin models from simplistic bilayer constructs to elaborate systems that incorporate both immune cells and active surface microbiota.

“Addressing these aspects, contemporary research is channeling resources into enhancing skin models from simplistic bilayer constructs to elaborate systems that incorporate both immune cells and active surface microbiota.”

May combine two claims.

Activation of WNT signaling pathway in hPSC-derived skin organoids produces larger organoids without off-target cartilage differentiation.

“through the activation of the WNT signaling pathway. This approach produced larger organoids without off-target cartilage differentiation.”

• cites 22.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

Vascularization by skin-specific endothelial cells leads to improved mechanical properties.

“the skin graft was further vascularized by skin-specific endothelial cells, leading to enhanced deposition of the ECM, improved mechanical properties, and site-specific differences in cellular and ECM organization.”

• cites 61.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

It was applied to study atopic dermatitis.

“but was also applied to the study of atopic dermatitis.”

• cites 22.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

This enhances HSE model toward more authentic skin-like configuration.

“thereby enhancing the current HSE model toward a more authentic skin-like configuration.”

• cites 62.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Lewis team developed human skin models with distinct rete ridges using 3D-printed stamps and micromolding.

“Lewis team developed human skin models featuring distinct rete ridges between the epidermal and dermal layers by employing 3D-printed stamps in conjunction with a micromolding technique.”

• cites 62.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Pappalardo et al. developed large-scale personalized edgeless wearable human skin grafts.

“Pappalardo et al. reported the development of large-scale personalized edgeless wearable human skin grafts.”

• cites 61.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

Rete ridges exhibited rounded attributes with controlled geometry and periodicity.

“The resulting rete ridges exhibited rounded attributes with precisely controlled geometry and periodicity within the dermal layer”

• cites 62.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

hPSC-derived skin organoid model has high fidelity in mimicking fetal skin and hair follicle development.

“confirming its high fidelity in mimicking fetal skin and hair follicle development from early to late time points”

• cites 64.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

ALI plays a critical role in promoting the differentiation of skin-relevant epithelial organoids.

“it further illustrates the critical role of ALI in promoting the differentiation of skin-relevant epithelial organoids.”

• cites 23.•Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Conjunctiva organoids provide a versatile platform for studying conjunctival physiology.

“and provide a versatile platform for studying conjunctival physiology.”

• cites 23.•Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

In vitro models exhibit cellular stress.

“while also highlighting cellular stress within in vitro models.”

• cites 44.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Mouse and human conjunctiva organoids recapitulate key features of conjunctival epithelium.

“It demonstrates that these organoids recapitulate key features of the conjunctival epithelium”

• cites 23.•Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

This study is the first comprehensive multiomic reference atlas of human prenatal skin (7-16 PCW).

“As the first comprehensive multiomic reference atlas of human prenatal skin (7–16 post-conception weeks)”

• cites 64.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The first hPSC-derived hair-bearing skin organoids were a breakthrough in 2020.

“Following the breakthrough of the first hPSC-derived hair-bearing skin organoids in 2020”

• cites 20.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Integrating an appropriate microbiota into an in vitro human skin model could significantly enhance its ability to replicate in vivo conditions more accurately.

“integrating an appropriate microbiota into an in vitro human skin model could significantly enhance its ability to replicate in vivo conditions more accurately.”

• cites 75.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

Vascularization by skin-specific endothelial cells leads to enhanced ECM deposition.

“the skin graft was further vascularized by skin-specific endothelial cells, leading to enhanced deposition of the ECM, improved mechanical properties, and site-specific differences in cellular and ECM organization.”

• cites 61.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

This study provided the first imitation of skin's overall coordination and regional specificity.

“This study provided the first imitation of the skin ’ s overall coordination and regional specificity”

• cites 61.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Nagano et al. generated semi-autologous skin in vivo through niche encroachment.

“Nagano et al. recently succeeded in generating semi-autologous skin in vivo through niche encroachment”

• cites 74.••Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.