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Biomedicines
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New Advances in Wound Healing and Skin Regeneration
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New Advances in Wound Healing and Skin Regeneration

A special issue of Biomedicines (ISSN 2227-9059).

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 10945

Editors

Dr. Bingrong Zhou

E-Mail Website
Guest Editor
Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Interests: wound healing; skin regeneration; dermatology; scar prevention; stem cell therapy; biomaterials; chronic wound management
Special Issues, Collections and Topics in MDPI journals
Dr. Siqi Fu

E-Mail Website
Guest Editor
Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha 410011, China
Interests: wound healing; scar formation; hair transplantation; regeneration

Special Issue Information

Dear Colleagues,

Chronic wounds, burns, and skin injuries pose significant clinical challenges, often leading to prolonged patient suffering and increased healthcare burdens. Recent advancements in regenerative medicine, biomaterials, and cellular therapies have opened new avenues for enhancing wound healing and skin regeneration. This Special Issue aims to highlight cutting-edge research and innovative strategies that accelerate wound repair, prevent scarring, and restore skin functionality.  We invite contributions covering novel biomaterials (e.g., hydrogels, scaffolds), stem cell therapies, growth factor delivery systems, bioactive dressings, and tissue engineering approaches. Additionally, studies on molecular mechanisms, immune modulation, and emerging technologies (e.g., 3D bioprinting, gene therapy, and nanotechnology) in wound healing are welcome. Clinical trials, translational research, and interdisciplinary studies bridging biology, engineering, and medicine will also be considered. This Special Issue seeks to provide a comprehensive platform for researchers to share breakthroughs that could revolutionize wound care, offering faster healing, reduced complications, and improved patient outcomes.

Dr. Bingrong Zhou
Dr. Siqi Fu
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • wound healing
  • skin regeneration
  • biomaterials
  • stem cell therapy
  • tissue engineering
  • bioactive dressings
  • 3D bioprinting
  • growth factors
  • chronic wounds
  • regenerative medicine

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Published Papers (6 papers)

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Research

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17 pages, 3720 KB  
Article
Histological Evaluation of Mentha spicata Essential Oil in a Rat Excisional Wound Model with Network-Based Mechanistic Insights
by Cafer Yildirim, Nihal Kayir, Merve Gulsen Bal Albayrak, Ayse Hande Yozgat and Durul Seyma Sen
Biomedicines 2026, 14(4), 739; https://doi.org/10.3390/biomedicines14040739 - 24 Mar 2026
Viewed by 949
Abstract
Background/Objectives: Wound healing is a complex biological process involving inflammatory, proliferative, and remodeling phases. Plant-derived essential oils are increasingly investigated as topical therapeutic agents, although their biological effects are strongly influenced by composition and formulation. The present study evaluated the effects of [...] Read more.
Background/Objectives: Wound healing is a complex biological process involving inflammatory, proliferative, and remodeling phases. Plant-derived essential oils are increasingly investigated as topical therapeutic agents, although their biological effects are strongly influenced by composition and formulation. The present study evaluated the effects of topical Mentha spicata essential oil on cutaneous wound healing in a rat excisional wound model and explored potential molecular mechanisms using a network-based bioinformatic approach. Methods: Twenty-one male Wistar rats were randomly assigned to three groups and treated twice daily for 14 days with a formulation containing 5% Mentha spicata essential oil diluted in olive oil, olive oil alone, or no treatment. Wound healing was assessed through macroscopic monitoring and histological scoring. The chemical composition of the essential oil was characterized using gas chromatography–mass spectrometry analysis. Predicted molecular targets of the major monoterpenes were analyzed through protein interaction networks and pathway enrichment analysis. Results: Macroscopic wound closure progressed in all groups by day 14. Histological analysis revealed that the olive oil group showed more advanced collagen deposition, re-epithelialization, and granulation tissue maturation, whereas the Mentha spicata group displayed a more pronounced inflammatory and proliferative histological pattern. Network-based analysis highlighted signaling pathways related to receptor-mediated cellular responses as potential molecular mechanisms associated with early inflammatory and proliferative processes. Conclusions: These findings suggest that the biological effects of Mentha spicata essential oil in wound repair may be phase-dependent and influenced by concentration and formulation. The results support further studies aimed at optimizing dose and delivery strategies for essential oil–based wound therapies. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Regeneration)
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21 pages, 15475 KB  
Article
Cornus officinalis Fruit Extract as an AMPK-Associated Mitochondrial Bioenergetic Modulator in Skin Aging Models
by Rui Ye, Qianqian Wang, Le Du, Li Li and Fan Hu
Biomedicines 2026, 14(2), 403; https://doi.org/10.3390/biomedicines14020403 - 10 Feb 2026
Viewed by 999
Abstract
Background: Mitochondrial dysfunction is a fundamental driver of skin aging, making the enhancement of cellular bioenergetics an important strategy in dermocosmetic innovation. Cornus officinalis fruit extract (COFE), standardized for iridoid glycosides, was investigated for its ability to modulate mitochondrial function and counteract photo-oxidative [...] Read more.
Background: Mitochondrial dysfunction is a fundamental driver of skin aging, making the enhancement of cellular bioenergetics an important strategy in dermocosmetic innovation. Cornus officinalis fruit extract (COFE), standardized for iridoid glycosides, was investigated for its ability to modulate mitochondrial function and counteract photo-oxidative stress associated with skin aging. Methods: Human dermal fibroblasts were treated with COFE to evaluate mitochondrial bioactivation. Transcriptomic changes were assessed using RNA sequencing (RNA-seq), with key mitochondrial genes validated by qPCR. AMPK phosphorylation, intracellular ATP content, NAD+/NADH ratio, and mitochondrial membrane potential (ΔΨm) were quantified as functional indicators of mitochondrial performance. To examine anti-aging relevance, a reconstructed human epidermis model was challenged with UVA and retinol to induce photo-oxidative stress. COFE’s effects on inflammatory (IL-1α), hydration (AQP3), proliferation (Ki67), and barrier-related (PKCα) markers were subsequently analyzed. Results: COFE was associated with activation of AMPK signaling and coordinated upregulation of OXPHOS-related genes in dermal fibroblasts, increasing ATP by 30.00%, the NAD+/NADH ratio by 158.71%, and ΔΨm by 158.82%. It also reduced IL-1α and upregulated AQP3, Ki67, and PKCα in a UVA/retinol-challenged epidermis model. In vivo, a 1% COFE eye cream produced statistically significant improvements across hydration, barrier function, redness, skin tone, wrinkles, elasticity, and periorbital contour after 28 days. Conclusions: COFE functions as an AMPK-associated mitochondrial bioenergetic modulator that enhances cellular energy metabolism and mitigates photo-oxidative stress in skin-relevant experimental models. The concordance between mechanistic findings and clinical outcomes supports COFE as a promising anti-aging active ingredient for dermocosmetic applications. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Regeneration)
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21 pages, 3557 KB  
Article
Screening and Functional Analysis of tsRNAs Associated with Diabetic Foot Ulcer Tissues
by Xiaona He, Yufei Chen, Lihong Liu, Siqi Fu, Yuyi Tian, Yihan Lin, Shang Zhu, Luhong Dai and Xiaojia Wen
Biomedicines 2025, 13(12), 2887; https://doi.org/10.3390/biomedicines13122887 - 26 Nov 2025
Viewed by 783
Abstract
Background: Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, and its inability to heal is closely linked to vascular pathology. However, the specific molecular regulatory networks involved remain unclear. This study hypothesizes that tRNA-derived small RNAs (tsRNAs) may be [...] Read more.
Background: Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, and its inability to heal is closely linked to vascular pathology. However, the specific molecular regulatory networks involved remain unclear. This study hypothesizes that tRNA-derived small RNAs (tsRNAs) may be associated with endothelial dysfunction in DFU. Methods: RNA sequencing (RNA-seq) was performed on DFU (n = 3) and healthy foot skin (n = 3) samples. Bioinformatics analysis identified differential expression of tsRNAs, with the ten most significantly differentially expressed tsRNAs validated by qRT-PCR. Target gene prediction and GO/KEGG enrichment analysis were then conducted on the four tsRNAs that demonstrated significant differential expression, as confirmed by qRT-PCR. Results: The results revealed that there were 49 differentially expressed tsRNAs between the two groups of samples. qRT-PCR validation confirmed that the expression trends of ten tRNAs were consistent with sequencing results. Among these, the 4770 potential target genes of four tRNAs exhibiting significant expression differences primarily encompassed the cell growth factor family and the Smad protein family. GO analysis revealed that the target genes were located mainly in the cytoplasm and organelle membranes and functioned by specifically binding to DNA in the transcriptional regulatory regions. KEGG pathway enrichment revealed that the differential tsRNAs were closely associated with pathways involved in cytoplasmic lysis and phagocytosis and the transforming growth factor beta (TGF-β) signaling pathway. Conclusions: This study systematically reveals the differential expression profile of tissue-specific tsRNAs in DFU tissue, thereby enriching the molecular pathological theory underlying the poor healing capacity of DFU. It also provides experimental evidence for the clinical translation of tsRNAs as early diagnostic markers for DFU. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Regeneration)
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23 pages, 3989 KB  
Article
A Hot-Spring Water Improves Inflammatory Conditions in an Injury-Induced Atopic Dermatitis Mouse Model by Regulating Skin Barrier Function
by Yoko Naito, Abdullah Md. Sheikh, Jubo Bhuiya, Fatema Binte Abdullah, Jerin Fahmida, Shatera Tabassum, Hiro Tamegai, Kenichi Iwasa, Shozo Yano and Atsushi Nagai
Biomedicines 2025, 13(11), 2707; https://doi.org/10.3390/biomedicines13112707 - 4 Nov 2025
Viewed by 3485
Abstract
Background: Atopic dermatitis (AD) is a common inflammatory skin condition in which skin barrier function plays a crucial role. Hot spring water is known for its beneficial effects on skin health. This study investigates the impact of a hot spring water on [...] Read more.
Background: Atopic dermatitis (AD) is a common inflammatory skin condition in which skin barrier function plays a crucial role. Hot spring water is known for its beneficial effects on skin health. This study investigates the impact of a hot spring water on AD pathology, focusing on skin barrier function. Methods: Using the tape-stripping method, we induced an AD mouse model, treated the mice with either hot-spring water or tap water, and assessed time-dependent changes in skin barrier function, histology, and AD-related proteins. Results: Transepithelial water loss (TEWL) was significantly increased after tape-stripping, which began to decrease from day 2 in both treatment groups. On day 3, water loss was significantly decreased in hot-spring-treated mice than tap water-treated mice. Histological analysis revealed thickening and vacuolization of the stratum spinosum from day 2, becoming more pronounced on day 3 in tap-water-treated mice. However, in hot-spring-treated mice, the stratum spinosum was significantly less thickened, and the stratum granulosum was better formed. Immunostaining showed that transient receptor potential vanilloid 4 (TRPV4) levels decreased at day 2 but returned to baseline by day 3, with no significant differences between groups. Filaggrin, a key skin barrier protein, was markedly low in tape-stripped areas at day 0, but increased progressively, with a higher level in the upper epidermis of hot-spring-treated mice compared to tap-water-treated counterparts. Additionally, hot spring water treatment significantly reduced CD8+ T cell numbers and IL-4 cytokine levels, mitigating inflammation. Conclusions: Threfore, hot spring water enhances skin barrier recovery and reduces inflammation in AD. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Regeneration)
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16 pages, 2928 KB  
Article
Immunomodulatory Potential of a Composite Amniotic Membrane Hydrogel for Wound Healing: Effects on Macrophage Cytokine Secretion
by Tao Wang, Zhiyuan Zhu, Wei Hua and Siliang Xue
Biomedicines 2025, 13(10), 2574; https://doi.org/10.3390/biomedicines13102574 - 21 Oct 2025
Cited by 1 | Viewed by 1314
Abstract
Background: The human acellular amniotic membrane (HAAM) is widely used as a decellularized bioscaffold in tissue engineering to promote wound healing, but its clinical application is limited by poor mechanical properties, rapid degradation, and handling difficulties. This study aimed to develop a modified [...] Read more.
Background: The human acellular amniotic membrane (HAAM) is widely used as a decellularized bioscaffold in tissue engineering to promote wound healing, but its clinical application is limited by poor mechanical properties, rapid degradation, and handling difficulties. This study aimed to develop a modified amniotic membrane-based composite material loaded with vascular endothelial growth factor (VEGF) and the Notch signaling inhibitor N-[N-(3,5-difluorophenacetyl)-Lalanylhydrazide]-Sphenylglycine t-butyl ester (DAPT) to enhance wound healing by modulating macrophage polarization and cytokine secretion. Methods: VEGF-loaded gellan gum-hyaluronic acid (GG-HA) hydrogels (VEGF-GG-HA) and DAPT-loaded HAAM (DAPT-HAAM) were prepared and combined to form a novel composite material (VEGF-GG-HA & DAPT-HAAM). The morphology and microstructure of the materials were characterized using scanning electron microscopy. In vitro studies were conducted using the human monocytic cell line (Tohoku Hospital Pediatrics-1, THP-1) to evaluate the effects of the materials on cell viability, cytokine secretion, and protein expression. Assessments included CCK-8 assays, ELISA, quantitative real-time PCR, Western blot analysis, and immunohistochemical staining. Results: The composite material VEGF-GG-HA & DAPT-HAAM exhibited good biocompatibility and significantly promoted THP-1 cell proliferation compared to control and single-component groups. It enhanced the secretion of IL-10, TNF-α, TGF-β, MMP1, and MMP3, while suppressing excessive TGF-β overexpression. The material also modulated macrophage polarization, showing a trend toward anti-inflammatory M2 phenotypes while maintaining pro-inflammatory signals (e.g., TNF-α) for a balanced immune response. Conclusions: The modified amniotic membrane hydrogel composite promotes wound healing through a phased immune response: it modulates macrophage polarization (balancing M1 and M2 phenotypes), enhances cytokine and matrix metalloproteinase secretion, and controls TGF-β levels. These effects contribute to improved vascular remodeling, reduced fibrosis, and prevention of scar formation, demonstrating the potential for enhanced wound management. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Regeneration)
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Review

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13 pages, 248 KB  
Review
Open Pilonidal Excision as a Translational Human Model for Wound Healing and Skin Regeneration Research
by Dimitrios Vardakostas, Zoe Garoufalia, Anastassios Philippou and Dimitrios Mantas
Biomedicines 2026, 14(4), 751; https://doi.org/10.3390/biomedicines14040751 - 26 Mar 2026
Viewed by 604
Abstract
Background/Objectives: Wound healing is a complex biological process involving coordinated interactions among inflammatory cells, growth factors, extracellular matrix components, and resident tissue cells. Despite significant advances in experimental research, translation of these findings into clinical practice remains limited, partly due to the lack [...] Read more.
Background/Objectives: Wound healing is a complex biological process involving coordinated interactions among inflammatory cells, growth factors, extracellular matrix components, and resident tissue cells. Despite significant advances in experimental research, translation of these findings into clinical practice remains limited, partly due to the lack of reproducible and ethically accessible human wound models. Pilonidal disease, a chronic inflammatory condition of the sacrococcygeal region, is frequently treated by surgical excision with healing by secondary intention. The resulting open wound provides a unique opportunity to study the natural progression of human tissue repair. Methods: This narrative review examines current knowledge on wound-healing physiology, commonly used experimental wound models, and clinical studies related to pilonidal disease. Evidence from experimental, translational, and clinical literature was evaluated to explore the potential of open pilonidal excision wounds as a standardized human model for wound-healing research. Results: Following open excision, healing typically occurs within 4–10 weeks through the classical phases of inflammation, proliferation, and tissue remodeling. During this period, the wound remains externally accessible, allowing repeated clinical observation and serial collection of tissue samples, wound fluid, and exudate. This accessibility facilitates investigation of key biological processes, including angiogenesis, fibroblast proliferation, epithelial migration, cytokine signaling, and extracellular matrix remodeling. Compared with in vitro systems and animal models, the open pilonidal wound offers direct insight into human wound biology under clinically relevant conditions. Conclusions: Open pilonidal excision wounds constitute a reproducible and ethically feasible in vivo human model for translational wound-healing research. This model may support biomarker discovery and contribute to the development of new therapeutic strategies for impaired healing and chronic wounds. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Regeneration)
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