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Cellular and Molecular Mechanisms in Wound Healing

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 5164

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Guest Editor
U.S. Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA
Interests: burn wound healing; adipose derived stem cells; hydrogels; regenerative medicine; skin tissue engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The healing of skin wounds, both acute and chronic, is recognized by the World Health Organization as a global unmet need. There are a variety of therapeutic options available to improve the healing process. However, this Special Issue will focus on cellular and molecular mechanisms in wound responses. Biomaterials and cells, including stem cells, are core elements of translational biomedical sciences and have provided us with a plethora of knowledge necessary to develop various technologies for wound healing and the regeneration of skin. Recent research advancements in novel wound healing platforms, ranging from bio-inspired materials to cell-derived matrices, have generated a paradigm shift in the field of wound healing. We also welcome studies on cell patterning using micro/nanomaterial-based scaffolding architectures and those utilizing hybrid scaffolding strategies to enable fine-tuning of the wound microenvironment into in situ multicellular tissues through the “body as a bioreactor” concept.

The goal of this Special Issue “Cellular and Molecular Mechanisms in Wound Healing” is to provide the audience with a taste of the promising recent novel strategies that have greatly advanced the field of wound healing, resulting in improved quality of life.

Dr. Shanmugasundaram Natesan
Guest Editor

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Keywords

  • wound healing
  • stem cells
  • tissue regeneration

Published Papers (3 papers)

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Research

25 pages, 7562 KiB  
Article
Emerging Effects of Resveratrol Derivatives in Cells Involved in Oral Wound Healing: A Preliminary Study
by Emira D’Amico, Tania Vanessa Pierfelice, Rosa Amoroso, Ivana Cacciatore, Camillo D’Arcangelo, Stefania Lepore, Simonetta D’Ercole, Natalia Di Pietro, Annalisa Di Rienzo, Morena Petrini, Adriano Piattelli, Alessia Ricci, Susi Zara, Antonio Di Stefano, Giovanna Iezzi and Barbara De Filippis
Int. J. Mol. Sci. 2023, 24(4), 3276; https://doi.org/10.3390/ijms24043276 - 07 Feb 2023
Cited by 1 | Viewed by 1489
Abstract
Recently, there has been an increasing interest in finding new approaches to manage oral wound healing. Although resveratrol (RSV) exhibited many biological properties, such as antioxidant and anti-inflammatory activities, its use as a drug is limited by unfavorable bioavailability. This study aimed to [...] Read more.
Recently, there has been an increasing interest in finding new approaches to manage oral wound healing. Although resveratrol (RSV) exhibited many biological properties, such as antioxidant and anti-inflammatory activities, its use as a drug is limited by unfavorable bioavailability. This study aimed to investigate a series of RSV derivatives (1aj) with better pharmacokinetic profiles. At first, their cytocompatibility at different concentrations was tested on gingival fibroblasts (HGFs). Among them, derivatives 1d and 1h significantly increased cell viability compared to the reference compound RSV. Thus, 1d and 1h were investigated for cytotoxicity, proliferation, and gene expression in HGFs, endothelial cells (HUVECs), and oral osteoblasts (HOBs), which are the main cells involved in oral wound healing. For HUVECs and HGFs, the morphology was also evaluated, while for HOBs ALP and mineralization were observed. The results showed that both 1d and 1h did not exert negative effects on cell viability, and at a lower concentration (5 µM) both even significantly enhanced the proliferative rate, compared to RSV. The morphology observations pointed out that the density of HUVECs and HGFs was promoted by 1d and 1h (5 µM) and mineralization was promoted in HOBs. Moreover, 1d and 1h (5 µM) induced a higher eNOS mRNA level in HUVECs, higher COL1 mRNA in HGFs, and higher OCN in HOBs, compared to RSV. The appreciable physicochemical properties and good enzymatic and chemical stability of 1d and 1h, along with their promising biological properties, provide the scientific basis for further studies leading to the development of RSV-based agents useful in oral tissue repair. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Wound Healing)
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16 pages, 2387 KiB  
Article
Alleviation of Severe Skin Insults Following High-Dose Irradiation with Isolated Human Fetal Placental Stromal Cells
by Boaz Adani, Eli Sapir, Evgenia Volinsky, Astar Lazmi-Hailu and Raphael Gorodetsky
Int. J. Mol. Sci. 2022, 23(21), 13321; https://doi.org/10.3390/ijms232113321 - 01 Nov 2022
Cited by 1 | Viewed by 1259
Abstract
Skin exposure to high-dose irradiation, as commonly practiced in radiotherapy, affects the different skin layers, causing dry and wet desquamation, hyperkeratosis fibrosis, hard to heal wounds and alopecia and damaged hair follicles. Fetal tissue mesenchymal stromal cells (f-hPSC) were isolated from excised human [...] Read more.
Skin exposure to high-dose irradiation, as commonly practiced in radiotherapy, affects the different skin layers, causing dry and wet desquamation, hyperkeratosis fibrosis, hard to heal wounds and alopecia and damaged hair follicles. Fetal tissue mesenchymal stromal cells (f-hPSC) were isolated from excised human fetal placental tissue, based on their direct migration from the tissue samples to the tissue dish. The current study follows earlier reports on for the mitigation of acute radiation syndrome following whole body high-dose exposure with remotely injected f-hPSC. Both the head only and a back skin flap of mice were irradiated with 16 &18 Gy, respectively, by 6MeV clinical linear accelerator electron beam. In both locations, the irradiated skin areas developed early and late radiation induced skin damages, including cutaneous fibrosis, lesions, scaring and severe hair follicle loss and reduced hair pigmentation. Injection of 2 × 106 f-hPSC, 3 and 8 weeks following 16 Gy head irradiation, and 1 and 4 weeks following the 18 Gy back skin only irradiation, resulted in significantly faster healing of radiation induced damages, with reduction of wet desquamation as measured by surface moisture level and minor recovery of the skin viscoelasticity. Detailed histological morphometry showed a clear alleviation of radiation induced hyperkeratosis in f-hPSC treated mice, with significant regain of hair follicles density. Following 16 Gy head irradiation, the hair follicles density in the scalp skin was reduced significantly by almost a half relative to the controls. A nearly full recovery of hair density was found in the f-hPSC treated mice. In the 18 Gy irradiated back skin, the hair follicles density dropped in a late stage by ~70% relative to naïve controls. In irradiated f-hPSC treated mice, it was reduced by only ~30% and was significantly higher than the non-treated group. Our results suggest that local injections of xenogeneic f-hPSC could serve as a simple, safe and highly effective non-autologous pro-regenerative treatment for high-dose radiation induced skin insults. We expect that such treatment could also be applied for other irradiated organs. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Wound Healing)
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12 pages, 3561 KiB  
Article
Prophylactic Instillation of Hydrogen-Rich Water Decreases Corneal Inflammation and Promotes Wound Healing by Activating Antioxidant Activity in a Rat Alkali Burn Model
by Momoko Kasamatsu, Takeshi Arima, Toyo Ikebukuro, Yuji Nakano, Yutaro Tobita, Masaaki Uchiyama, Akira Shimizu and Hiroshi Takahashi
Int. J. Mol. Sci. 2022, 23(17), 9774; https://doi.org/10.3390/ijms23179774 - 29 Aug 2022
Cited by 4 | Viewed by 1895
Abstract
Many studies have demonstrated the therapeutic effects of hydrogen in pathological conditions such as inflammation; however, little is known about its prophylactic effects. The purpose of this study is to investigate the prophylactic effects of hydrogen-rich water instillation in a rat corneal alkali [...] Read more.
Many studies have demonstrated the therapeutic effects of hydrogen in pathological conditions such as inflammation; however, little is known about its prophylactic effects. The purpose of this study is to investigate the prophylactic effects of hydrogen-rich water instillation in a rat corneal alkali burn model. Hydrogen-rich water (hydrogen group) or physiological saline (vehicle group) was instilled continuously to the normal rat cornea for 5 min. At 6 h after instillation, the cornea was exposed to alkali. The area of corneal epithelial defect (CED) was measured every 6 h until 24 h after alkali exposure. In addition, at 6 and 24 h after injury, histological and immunohistochemical observations were made and real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to investigate superoxide dismutase enzyme (SOD)1, SOD2, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA expression. CED at 12 h and the number of inflammatory infiltrating cells at 6 h after injury were significantly smaller in the hydrogen group than the vehicle group. Furthermore, SOD1 expression was significantly higher in the hydrogen group than the vehicle group at both 6 and 24 h, and the number of PGC-1α-positive cells was significantly larger in the hydrogen group than the vehicle group at 6 h after injury. In this model, prophylactic instillation of hydrogen-rich water suppressed alkali burn-induced inflammation, likely by upregulating expression of antioxidants such as SOD1 and PGC-1α. Hydrogen has not only therapeutic potential but also prophylactic effects that may suppress corneal scarring following injury and promote wound healing. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Wound Healing)
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