ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Organoids and Organ-On-A-Chip
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1621566
Engineering a 3D Wounded Skin Equivalent to Study Early Inflammatory and Regenerative Responses In Vitro
Provisionally accepted
- 1Leipzig University, Leipzig, Germany
- 2108 Hospital, Hanoi, Vietnam
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Traditional models for studying wound healing, including 2D cell cultures and animal models, present substantial limitations in mimicking human skin physiology. In this study, we present a three-dimensional wounded skin equivalent (3DWoundSE) composed of human cells as a physiologically relevant in vitro platform to investigate wound healing processes. The model builds upon a previously established 3D skin equivalent (3DSE) and incorporates a reproducible partial-thickness dermal punch wound. We characterised the 3DWoundSE using histology, cytotoxicity assays, immunofluorescence staining, and pro-inflammatory cytokine profiling at multiple time points post-wounding. Results revealed hallmark wound responses, including increased lactate dehydrogenase (LDH) and apoptosis-inducing factor (AIF) expression, dynamic Ki-67 proliferation changes, and a pro-inflammatory cytokine response, notably elevated IL-6, IL-8, IL-33 and TNF-α levels. Compared to the intact 3DSE, this 3DWoundSE demonstrated enhanced responsiveness to injury and cytotoxic stimuli, confirming its utility for early wound response assessment. This platform offers a reproducible and ethically sound alternative to animal models, with potential applications in dermatological research, drug development, and therapeutic screening.
Keywords: 3D skin equivalent, Wound Healing, Wound model, Cytokines, in vitro model, Bioengineered skin
Received: 01 May 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Nuwayhid, Ngoc-Huyen, Notov, Langer and Kurow. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rima Nuwayhid, Leipzig University, Leipzig, Germany
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