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Advances in Application of Natural Compounds in Skin Repair and...
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Advances in Application of Natural Compounds in Skin Repair and Regenerative Medicine

A Special Issue of Molecules (ISSN 1420-3049) belonging to the section "Applied Chemistry".

Deadline for manuscript submissions: closed (31 August 2026) | Viewed by 7824

Editor

Dr. Katarína Valachová

E-Mail Website
Guest Editor
Centre of Experimental Medicine of Slovak Academy of Sciences, Dubravska cesta 9, 84104 Bratislava, Slovakia
Interests: hyaluronan; reactive oxygen species; drugs; antioxidants; biopolymers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleague,

Natural compounds play a crucial role in promoting wound healing and skin regeneration by modulating key cellular and molecular processes involved in tissue repair. Naturally derived molecules, including polysaccharides, peptides, polyphenols, vitamins, and growth factors, can stimulate multiple phases of wound healing, such as hemostasis, inflammation resolution, re-epithelialization, angiogenesis, and extracellular matrix remodeling.

Antioxidant and anti-inflammatory natural compounds help mitigate oxidative stress and chronic inflammation, while antimicrobial natural compounds contribute to infection prevention in both acute and chronic wounds. When incorporated into advanced delivery systems—such as hydrogels, nanofibers, scaffolds, and films—natural compounds can be protected from degradation, precisely targeted, and released in a controlled manner at the wound site, enhancing stability and therapeutic efficacy.

Current research also emphasizes the development of cell-instructive materials incorporating natural compounds that provide biochemical and biophysical cues to guide stem cell recruitment and differentiation, enabling true tissue regeneration rather than simple wound closure. This Special Issue focuses on the sources, mechanisms of action, and delivery strategies of natural compounds for wound healing and skin regeneration, while highlighting current challenges and future directions toward safe, effective, and clinically translatable therapies.

Dr. Katarína Valachová
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

  • angiogenesis
  • anti-inflammatory agents
  • antioxidants
  • drug delivery systems
  • growth factors
  • natural compounds
  • skin regeneration
  • tissue engineering
  • wound healing

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Published Papers (5 papers)

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Research

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16 pages, 26932 KB  
Article
Ganoderic Acid A Reverses Ultraviolet B Induced Hyperpigmentation via Multi-Targeted Regulation of Mitochondrial Homeostasis and Inflammation
by Jingting Wang, Yuerong Qian, Qingna Gong, Rui He, Shanli Tian, Nannan Yu, Yanan Xi, Qiqi Wu, Guang-Li Wang and Jing Wang
Molecules 2026, 31(15), 2705; https://doi.org/10.3390/molecules31152705 - 4 Aug 2026
Viewed by 1218
Abstract
Background: Conventional tyrosinase (TYR) inhibitors irritate skin and trigger rebound pigmentation, necessitating safer and more effective depigmenting agents. Methods: Biocompatibility was assessed by cell viability. Melanin content and TYR activity were measured spectrophotometrically. Reactive oxygen species (ROS), adenosine triphosphate (ATP), and inflammatory cytokines [...] Read more.
Background: Conventional tyrosinase (TYR) inhibitors irritate skin and trigger rebound pigmentation, necessitating safer and more effective depigmenting agents. Methods: Biocompatibility was assessed by cell viability. Melanin content and TYR activity were measured spectrophotometrically. Reactive oxygen species (ROS), adenosine triphosphate (ATP), and inflammatory cytokines were detected by fluorescence, luminescence, and ELISA. Western blot and RT-qPCR assessed oxidative stress, inflammatory, and melanogenic targets. Molecular docking simulated Ganoderic Acid A (GAA) interactions with key proteins. Results: GAA exhibits good biocompatibility, inhibits melanin synthesis and TYR activity in B16-F10 cells, and reverses ultraviolet B-induced pigmentation. Mechanistically, GAA restores mitochondrial homeostasis by scavenging ROS, replenishing ATP, activating the nuclear factor erythroid 2-related factor 2 (Nrf2) axis, and inhibiting nuclear factor kappa-B (NF-κB) and cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to regulate the inflammatory microenvironment. This synergistic regulation inhibits the mitogen-activated protein kinase (MAPK) signaling pathway and down-regulates the microphthalmia-associated transcription factor (MITF) transcriptional network and the expression of TYR, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). Conclusion: GAA eliminates ultraviolet B-induced hyperpigmentation through a multi-target mechanism of mitochondrial repair, inflammation inhibition, and direct binding to tyrosinase, and is a potential natural candidate drug for the treatment of skin diseases. Full article
(This article belongs to the Special Issue Advances in Application of Natural Compounds in Skin Repair and Regenerative Medicine)
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20 pages, 6125 KB  
Article
Enzymatic Fructosylation of EGCG Significantly Enhances Its Stability for Skin Barrier Repair and Anti-Aging Activities
by Xiaojun Zhang, Bohan Yang, Qingna Gong, Nianqing Zhu, Yuan-Cheng Huang, Jian-Ming Deng, Min Yu, Xiaodong Yan and Jing Wang
Molecules 2026, 31(13), 2381; https://doi.org/10.3390/molecules31132381 - 6 Jul 2026
Viewed by 447
Abstract
(-)-Epigallocatechin gallate (EGCG) possesses potent bioactivities but its applications in functional cosmetics is severely limited by its poor water solubility and chemical instability. To overcome these challenges, this study engineered a recombinant levansucrase from Vibrio natriegens to catalyze the transfructosylation of EGCG. The [...] Read more.
(-)-Epigallocatechin gallate (EGCG) possesses potent bioactivities but its applications in functional cosmetics is severely limited by its poor water solubility and chemical instability. To overcome these challenges, this study engineered a recombinant levansucrase from Vibrio natriegens to catalyze the transfructosylation of EGCG. The conversion rate of EGCG to fructoside reached 65.59%. The purified product was unequivocally identified as EGCG-1F, with a fructosyl group linked to the 3′-hydroxyl group. Compared to pristine EGCG, EGCG-1F exhibited remarkably enhanced water solubility (96.6-fold that of EGCG) and aqueous stability under acidic and thermal conditions. Biological evaluation revealed that EGCG-1F significantly enhanced HaCaT cell migration, upregulated the expression of basement membrane-associated collagens in ultraviolet B-damaged HaCaT cells, and modulated ultraviolet A-induced senescence in human dermal fibroblasts by type I collagen, type III collagen and matrix metalloproteinase-1 balance. This study demonstrates that enzymatic fructosylation is an effective approach to generate a stable and safe EGCG derivative with potential applications in skin barrier repair and anti-aging functional cosmetics. Full article
(This article belongs to the Special Issue Advances in Application of Natural Compounds in Skin Repair and Regenerative Medicine)
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31 pages, 12973 KB  
Article
Novasomal Gel for Enhanced Dermal Delivery and Antibacterial Efficacy of Cinnamic Acid
by Rana Alanazi, Shahad Althumali, Abeer Albalawi, Ghala Alqubaydhi, Mona Qushawy, Ayman Salama, Mona F. Arafa, Helal F. Hetta, Yasmin N. Ramadan, Yasmin Mortagi and Ghareb M. Soliman
Molecules 2026, 31(13), 2277; https://doi.org/10.3390/molecules31132277 - 29 Jun 2026
Viewed by 748
Abstract
While bacterial skin infections are highly prevalent worldwide, their eradication with conventional topical medications remains highly challenging. Cinnamic acid (CA) is a naturally occurring molecule with interesting antibacterial properties, but its efficacy is hindered by poor aqueous solubility and skin permeability. To overcome [...] Read more.
While bacterial skin infections are highly prevalent worldwide, their eradication with conventional topical medications remains highly challenging. Cinnamic acid (CA) is a naturally occurring molecule with interesting antibacterial properties, but its efficacy is hindered by poor aqueous solubility and skin permeability. To overcome these challenges, CA was encapsulated within novasomes, which are multilamellar vesicles composed of fatty acids, cholesterol, and nonionic surfactants. The novasomes were optimized using a 23 factorial design and the optimized formulation was incorporated in a carbopol gel base and evaluated for spreadability, rheological properties, drug release, ex vivo skin permeation and deposition, and antibacterial efficacy. The optimized novasomes featured desirable properties, including high drug entrapment (94.75 ± 0.05%), nanometric particle size (123.80 ± 1.44 nm), and negative zeta potential (−36.63 ± 0.61 mV). CA novasomal gel exhibited shear-thinning behavior, coupled with thixotropic properties. It also achieved approximately 1.7-fold higher flux through rat skin compared with the free CA gel. Moreover, the novasomes showed a two-fold reduction in the minimum inhibitory concentration of the drug against E. coli compared with the drug suspension. These findings support the potential of CA novasomal gel to enhance its antibacterial activity and skin permeability, making it a promising approach for topical delivery of this naturally occurring compound. Full article
(This article belongs to the Special Issue Advances in Application of Natural Compounds in Skin Repair and Regenerative Medicine)
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17 pages, 5715 KB  
Article
The Effects and Molecular Mechanisms of a Peptide from Periplaneta americana L. in Skin Wound Healing
by Honghong Qiu, Yanyan Chen, Wei Zhang, Bin Dong, Dongli Zhang, Renjin Tang and Zhong Liu
Molecules 2026, 31(8), 1355; https://doi.org/10.3390/molecules31081355 - 21 Apr 2026
Cited by 1 | Viewed by 1049
Abstract
Periplaneta americana extract can promote wound healing and may play an important role in skin wound healing. In this study, we identified a peptide (DL-13) from Periplaneta americana L. and explored its role and mechanisms in skin wound healing. In vitro, the effects [...] Read more.
Periplaneta americana extract can promote wound healing and may play an important role in skin wound healing. In this study, we identified a peptide (DL-13) from Periplaneta americana L. and explored its role and mechanisms in skin wound healing. In vitro, the effects of DL-13 on proliferation, migration, and related gene/protein expression in HaCaT keratinocytes were assessed via qRT-PCR and Western blot. In vivo, rat wound healing assays confirmed its efficacy. Results showed DL-13 accelerated rat wound healing. In in vitro studies, DL-13 activated EGFR and its downstream PI3K/AKT/mTOR, ERK/MAPK, and JAK2/STAT3 pathways, upregulated EMT-related proteins (N-cadherin, MMP-2, p-FAK, β-catenin), partially regulated macrophage cytokine secretion, and promoted HaCaT proliferation/migration, thereby facilitating re-epithelialization at skin injury sites. Overall, DL-13 may enhance the function of HaCaT cells by activating the EGFR signaling pathway and regulate inflammatory factors in macrophages, thereby promoting the healing of skin wounds in rats. The results of this study will lay an experimental and scientific foundation for the discovery of new compounds for wound healing and their application. Full article
(This article belongs to the Special Issue Advances in Application of Natural Compounds in Skin Repair and Regenerative Medicine)
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Review

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32 pages, 1957 KB  
Review
Chronic Wound Healing: Research Advances from Pathological Mechanisms to Natural Herbal Active Ingredients and Material Delivery Systems
by Mengqing Yuan, Yufeng Liu, Xiaoyin Peng, Zhenjun Li and Mingsheng Lei
Molecules 2026, 31(6), 1024; https://doi.org/10.3390/molecules31061024 - 19 Mar 2026
Cited by 7 | Viewed by 3816
Abstract
Chronic wound healing is a complex pathological process driven by multiple factors, presenting a significant global healthcare challenge. It not only severely compromises patients’ quality of life but also imposes a substantial socioeconomic burden. In recent years, with deepening insights into the wound [...] Read more.
Chronic wound healing is a complex pathological process driven by multiple factors, presenting a significant global healthcare challenge. It not only severely compromises patients’ quality of life but also imposes a substantial socioeconomic burden. In recent years, with deepening insights into the wound microenvironment, composite therapeutic strategies combining natural herbal medicines and their active components with modern biomaterials have offered novel approaches to overcoming refractory wounds caused by diabetic ulcers, vascular lesions, burns, and infections. This paper first outlines the biological foundations of normal wound healing, emphasizing the core mechanisms underlying chronic wound persistence—including persistent inflammatory responses, impaired tissue repair, and cellular dysfunction. Building upon this foundation, the article systematically reviews the existing therapeutic approaches (such as conventional debridement) before focusing on the classification and application of novel biomaterials. It further analyzes the synergistic therapeutic advantages of using materials as delivery systems for natural bioactive compounds. This combined approach enables targeted regulation of the chronic wound microenvironment, synergistically promoting cell proliferation and migration to accelerate healing. Deepening our understanding of the biological mechanisms underlying chronic wounds, coupled with advanced biomaterial technologies, will propel clinical treatment toward more precise and efficient outcomes. Full article
(This article belongs to the Special Issue Advances in Application of Natural Compounds in Skin Repair and Regenerative Medicine)
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