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Novel Natural Compound for Wound and Tissue Repair and Regeneration

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

Deadline for manuscript submissions: closed (15 June 2023) | Viewed by 39902

Special Issue Editors


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Guest Editor

Special Issue Information

Dear Colleagues,

Wound healing is of great importance for skin medicine, with particular interest focused on natural compounds. 

Numerous studies have recognized the potential of natural products in terms of antibacterial, antioxidant, immunomodulatory, and pro-collagen synthesis properties as wound-healing agents.

The therapeutic virtues of natural compounds have been rediscovered by the medical profession and are gaining acceptance for treating wounds, ulcers, and other surface infections.

In spite of the extensive literature available on natural compounds’ clinical uses, the subjacent mechanisms are still largely unknown. With the growing interest for natural product utilizations and the belief that they are safer than standard therapies, it is crucial to increase our knowledge of their efficacy and side effects.

Thus, original articles and reviews investigating the positive effects of natural compounds on wound healing along with the involved cellular and molecular mechanisms will be suitable for this Special Issue.

Dr. Elia Ranzato
Dr. Simona Martinotti
Guest Editors

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Keywords

  • wound repair
  • tissue regeneration
  • natural compounds
  • phytochemicals
  • molecular mechanisms

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Published Papers (17 papers)

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19 pages, 17399 KiB  
Article
Anti-Inflammatory and Histological Analysis of Skin Wound Healing through Topical Application of Mexican Propolis
by Daniela Balderas-Cordero, Octavio Canales-Alvarez, Roberto Sánchez-Sánchez, Alejandro Cabrera-Wrooman, Maria Margarita Canales-Martinez and Marco Aurelio Rodriguez-Monroy
Int. J. Mol. Sci. 2023, 24(14), 11831; https://doi.org/10.3390/ijms241411831 - 23 Jul 2023
Cited by 6 | Viewed by 3331
Abstract
Skin wound healing is a complex biochemical process of tissue repair and remodeling in response to injury. Currently, the drugs used to improve the healing process are inaccessible to the population, are costly, and have side effects, making the search for new treatment [...] Read more.
Skin wound healing is a complex biochemical process of tissue repair and remodeling in response to injury. Currently, the drugs used to improve the healing process are inaccessible to the population, are costly, and have side effects, making the search for new treatment alternatives necessary. Propolis is a natural product produced by bees that is widely recognized and used in folk medicine for its multiple biomedical activities. However, therapeutic information regarding Mexican propolis is limited. This study aimed to evaluate the wound-healing effect of the Chihuahua ethanolic extract of propolis (ChEEP). Macroscopic and histological analyses were performed using a mouse wound-healing model. The topic acute toxicity assay showed that propolis at 10% w/v had no toxic effects. ChEEP has antibacterial activity against the Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis. Moreover, it exhibited good anti-inflammatory activity evaluated through mouse ear edema induced by 12-O-tetradeca-noylphorbol-13-acetate (TPA). A full-thickness incision lesion was created in mice and treated topically with 10% ChEEP. At Day 14 post-treatment, it was observed that propolis increased wound contraction and reduced healing time and wound length; furthermore, propolis increased the tensile strength of the wound, as determined with the tensiometric method, and promoted the formation of type I collagen at the site of injury, as evaluated with Herovici stain. These findings suggest that the topical administration of ChEEP can improve skin wound healing, probably due to the synergistic effect of its components, mainly polyphenols, in different steps of the wound-healing process. It should be noted this is the first time that the wound-healing activity of a Mexican propolis has been evaluated. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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21 pages, 7407 KiB  
Article
Biological Activity of Bursera schlechtendalii Essential oil and the Roles of Its Chemical Components in the Wound Healing Process
by Lesslie Espinosa-Espinosa, Octavio Canales-Alvarez, Marlene Guadalupe Rodríguez-López, César Antonio Flores-Tinajero, Maria Margarita Canales-Martinez and Marco Aurelio Rodriguez-Monroy
Int. J. Mol. Sci. 2023, 24(13), 11040; https://doi.org/10.3390/ijms241311040 - 03 Jul 2023
Viewed by 1178
Abstract
Essential oils are composed of terpenes, some of which have properties related to healing. Bursera schlechtendalii essential oil (BSEO) is used to heal superficial wounds. However, there have been no studies verifying this property. The objectives of this study were to evaluate the [...] Read more.
Essential oils are composed of terpenes, some of which have properties related to healing. Bursera schlechtendalii essential oil (BSEO) is used to heal superficial wounds. However, there have been no studies verifying this property. The objectives of this study were to evaluate the healing activity of BSEO in a murine model and to propose the roles of its chemical components in this process. Healing activity was evaluated by an incision model, histological analysis was performed, and tensile strength and antibacterial activity were measured. The chemical composition of BSEO was determined by gas chromatography coupled with mass spectrometry (GC–MS), and the mechanisms of action of each chemical component during the phases of the healing process were proposed. In addition, acute dermal toxicity was evaluated. BSEO showed better wound closure at the macroscopic, histological, and tensile strength levels compared to controls and had an antibacterial effect. The major compound in BSEO was α-phellandrene. However, most of the monoterpenes identified in BSEO were in agreement with information found in the literature, so the possibility of synergy between the chemical components and their different targets in the healing process was schematically proposed. BSEO was shown to be safe in the dermal toxicity evaluation. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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13 pages, 2566 KiB  
Article
PRP of T2DM Patient Immobilized on PCL Nanofibers Stimulate Endothelial Cells Proliferation
by Anastasiya O. Solovieva, Natalia A. Sitnikova, Vadim V. Nimaev, Elena A. Koroleva and Anton M. Manakhov
Int. J. Mol. Sci. 2023, 24(9), 8262; https://doi.org/10.3390/ijms24098262 - 05 May 2023
Cited by 2 | Viewed by 1066
Abstract
Diabetic foot ulcers (DFU) are a common complication of Type 2 Diabetes Mellitus (T2DM). Development of bioactive wound healing covers is an important task in medicine. The use of autologous platelet-rich plasma (PRP) consisting of growth factors, cytokines and components of extracellular matrix [...] Read more.
Diabetic foot ulcers (DFU) are a common complication of Type 2 Diabetes Mellitus (T2DM). Development of bioactive wound healing covers is an important task in medicine. The use of autologous platelet-rich plasma (PRP) consisting of growth factors, cytokines and components of extracellular matrix is a perspective approach for DFU treatment, but we previously found that some T2DM PRP samples have a toxic effect on mesenchymal stem cells (MSCs) in vitro. Here, we covalently immobilized T2DM PRP proteins on polycaprolactone (PCL) nanofibers, and the growth of endothelial cells on the PCL-COOH-PRP was investigated. Additionally, the level of NO reflecting the cytotoxic effects of PRP, angiogenin, and VEGF levels were measured in T2DM PRP samples. The results showed that the application of PCL-COOH-PRP nanofibers allows to remove the cytotoxicity of T2DM PRP and to improve endothelial cell adhesion and proliferative activity. We showed that the origin of T2DM PRP (the level of PRP toxicity or presence/absence of DFU) does not influence the efficiency of cell growth on PCL-COOH-PRP, and on the level of angiogenin, vascular epidermal growth factor (VEGF) in PRP itself. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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19 pages, 2740 KiB  
Article
Understanding the Molecular Conformation and Viscoelasticity of Low Sol-Gel Transition Temperature Gelatin Methacryloyl Suspensions
by Cristina Padilla, Franck Quero, Marzena Pępczyńska, Paulo Díaz-Calderon, Juan Pablo Acevedo, Nicholas Byres, Jonny J. Blaker, William MacNaughtan, Huw E. L. Williams and Javier Enrione
Int. J. Mol. Sci. 2023, 24(8), 7489; https://doi.org/10.3390/ijms24087489 - 19 Apr 2023
Viewed by 1474
Abstract
For biomedical applications, gelatin is usually modified with methacryloyl groups to obtain gelatin methacryloyl (GelMA), which can be crosslinked by a radical reaction induced by low wavelength light to form mechanically stable hydrogels. The potential of GelMA hydrogels for tissue engineering has been [...] Read more.
For biomedical applications, gelatin is usually modified with methacryloyl groups to obtain gelatin methacryloyl (GelMA), which can be crosslinked by a radical reaction induced by low wavelength light to form mechanically stable hydrogels. The potential of GelMA hydrogels for tissue engineering has been well established, however, one of the main disadvantages of mammalian-origin gelatins is that their sol-gel transitions are close to room temperature, resulting in significant variations in viscosity that can be a problem for biofabrication applications. For these applications, cold-water fish-derived gelatins, such as salmon gelatin, are a good alternative due to their lower viscosity, viscoelastic and mechanical properties, as well as lower sol-gel transition temperatures, when compared with mammalian gelatins. However, information regarding GelMA (with special focus on salmon GelMA as a model for cold-water species) molecular conformation and the effect of pH prior to crosslinking, which is key for fabrication purposes since it will determine final hydrogel’s structure, remains scarce. The aim of this work is to characterize salmon gelatin (SGel) and salmon methacryloyl gelatin (SGelMA) molecular configuration at two different acidic pHs (3.6 and 4.8) and to compare them to commercial porcine gelatin (PGel) and methacryloyl porcine gelatin (PGelMA), usually used for biomedical applications. Specifically, we evaluated gelatin and GelMA samples’ molecular weight, isoelectric point (IEP), their molecular configuration by circular dichroism (CD), and determined their rheological and thermophysical properties. Results showed that functionalization affected gelatin molecular weight and IEP. Additionally, functionalization and pH affected gelatin molecular structure and rheological and thermal properties. Interestingly, the SGel and SGelMA molecular structure was more sensitive to pH changes, showing differences in gelation temperatures and triple helix formation than PGelMA. This work suggests that SGelMA presents high tunability as a biomaterial for biofabrication, highlighting the importance of a proper GelMA molecular configuration characterization prior to hydrogel fabrication. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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15 pages, 4832 KiB  
Article
Characterization and In Vivo Assay of Allantoin-Enriched Pectin Hydrogel for the Treatment of Skin Wounds
by Rosa Alicia Saucedo-Acuña, Karen Zulema Meza-Valle, Juan Carlos Cuevas-González, Elsa Gabriela Ordoñez-Casanova, Manuel Iván Castellanos-García, Erasto Armando Zaragoza-Contreras and Genaro Federico Tamayo-Pérez
Int. J. Mol. Sci. 2023, 24(8), 7377; https://doi.org/10.3390/ijms24087377 - 17 Apr 2023
Cited by 3 | Viewed by 2119
Abstract
This work describes a liquid allantoin-enriched pectin hydrogel with hydrophilic behavior that is supported by the presence of functional groups related to healing efficacy. A topical study shows the effect of the hydrogel application on surgically induced skin wound healing in a rat [...] Read more.
This work describes a liquid allantoin-enriched pectin hydrogel with hydrophilic behavior that is supported by the presence of functional groups related to healing efficacy. A topical study shows the effect of the hydrogel application on surgically induced skin wound healing in a rat model. Contact angle measurements confirm hydrophilic behavior (11.37°), while Fourier-transform infrared spectroscopy indicates the presence of functional groups related to the healing effectiveness (carboxylic acid and amine groups). Allantoin is distributed on the surface and inside the amorphous pectin hydrogel surrounded by a heterogeneous distribution of pores. This promotes wound drying with better interaction between the hydrogel and cells involved in the wound healing process. An experimental study with female Wistar rats indicates that the hydrogel improves wound contraction, reducing around 71.43% of the total healing time and reaching total wound closure in 15 days. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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17 pages, 2766 KiB  
Article
Comparison of the Effect of Different Conditioning Media on the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes: Towards Engineering Next-Generation Autologous Growth Factor Cocktails
by Philipp Moog, Jessica Hughes, Jun Jiang, Lynn Röper, Ulf Dornseifer, Arndt F. Schilling, Hans-Günther Machens and Ektoras Hadjipanayi
Int. J. Mol. Sci. 2023, 24(6), 5485; https://doi.org/10.3390/ijms24065485 - 13 Mar 2023
Cited by 1 | Viewed by 1168
Abstract
Hypoxia Preconditioned Plasma (HPP) and Serum (HPS) are regenerative blood-derived growth factor compositions that have been extensively examined for their angiogenic and lymphangiogenic activity towards wound healing and tissue repair. Optimization of these secretomes’ growth factor profile, through adjustments of the conditioning parameters, [...] Read more.
Hypoxia Preconditioned Plasma (HPP) and Serum (HPS) are regenerative blood-derived growth factor compositions that have been extensively examined for their angiogenic and lymphangiogenic activity towards wound healing and tissue repair. Optimization of these secretomes’ growth factor profile, through adjustments of the conditioning parameters, is a key step towards clinical application. In this study, the autologous liquid components (plasma/serum) of HPP and HPS were replaced with various conditioning media (NaCl, PBS, Glucose 5%, AIM V medium) and were analyzed in terms of key pro- (VEGF-A, EGF) and anti-angiogenic (TSP-1, PF-4) protein factors, as well as their ability to promote microvessel formation in vitro. We found that media substitution resulted in changes in the concentration of the aforementioned growth factors, and also influenced their ability to induce angiogenesis. While NaCl and PBS led to a lower concentration of all growth factors examined, and consequently an inferior tube formation response, replacement with Glucose 5% resulted in increased growth factor concentrations in anticoagulated blood-derived secretomes, likely due to stimulation of platelet factor release. Medium substitution with Glucose 5% and specialized peripheral blood cell-culture AIM V medium generated comparable tube formation to HPP and HPS controls. Altogether, our data suggest that medium replacement of plasma and serum may significantly influence the growth factor profile of hypoxia-preconditioned blood-derived secretomes and, therefore, their potential application as tools for promoting therapeutic angiogenesis. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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17 pages, 3443 KiB  
Article
Meta-Analysis of Cytotoxicity Studies Using Machine Learning Models on Physical Properties of Plant Extract-Derived Silver Nanoparticles
by Anjana S. Desai, Aparna Ashok, Zehra Edis, Samir Haj Bloukh, Mayur Gaikwad, Rajendra Patil, Brajesh Pandey and Neeru Bhagat
Int. J. Mol. Sci. 2023, 24(4), 4220; https://doi.org/10.3390/ijms24044220 - 20 Feb 2023
Cited by 4 | Viewed by 2017
Abstract
Silver nanoparticles (Ag-NPs) demonstrate unique properties and their use is exponentially increasing in various applications. The potential impact of Ag-NPs on human health is debatable in terms of toxicity. The present study deals with MTT(3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium-bromide) assay on Ag-NPs. We measured the [...] Read more.
Silver nanoparticles (Ag-NPs) demonstrate unique properties and their use is exponentially increasing in various applications. The potential impact of Ag-NPs on human health is debatable in terms of toxicity. The present study deals with MTT(3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium-bromide) assay on Ag-NPs. We measured the cell activity resulting from molecules’ mitochondrial cleavage through a spectrophotometer. The machine learning models Decision Tree (DT) and Random Forest (RF) were utilized to comprehend the relationship between the physical parameters of NPs and their cytotoxicity. The input features used for the machine learning were reducing agent, types of cell lines, exposure time, particle size, hydrodynamic diameter, zeta potential, wavelength, concentration, and cell viability. These parameters were extracted from the literature, segregated, and developed into a dataset in terms of cell viability and concentration of NPs. DT helped in classifying the parameters by applying threshold conditions. The same conditions were applied to RF to extort the predictions. K-means clustering was used on the dataset for comparison. The performance of the models was evaluated through regression metrics, viz. root mean square error (RMSE) and R2. The obtained high value of R2 and low value of RMSE denote an accurate prediction that could best fit the dataset. DT performed better than RF in predicting the toxicity parameter. We suggest using algorithms for optimizing and designing the synthesis of Ag-NPs in extended applications such as drug delivery and cancer treatments. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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18 pages, 4841 KiB  
Article
Approaches in Hydroxytyrosol Supplementation on Epithelial—Mesenchymal Transition in TGFβ1-Induced Human Respiratory Epithelial Cells
by Rabiatul Adawiyah Razali, Muhammad Dain Yazid, Aminuddin Saim, Ruszymah Bt Hj Idrus and Yogeswaran Lokanathan
Int. J. Mol. Sci. 2023, 24(4), 3974; https://doi.org/10.3390/ijms24043974 - 16 Feb 2023
Cited by 3 | Viewed by 1334
Abstract
Hydroxytyrosol (HT) is an olive polyphenol with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of HT treatment on epithelial–mesenchymal transition (EMT) in primary human respiratory epithelial cells (RECs) isolated from human nasal turbinate. HT dose–response study and growth kinetic [...] Read more.
Hydroxytyrosol (HT) is an olive polyphenol with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of HT treatment on epithelial–mesenchymal transition (EMT) in primary human respiratory epithelial cells (RECs) isolated from human nasal turbinate. HT dose–response study and growth kinetic study on RECs was performed. Several approaches on HT treatment and TGFβ1 induction with varying durations and methods was studied. RECs morphology and migration ability were evaluated. Vimentin and E-cadherin immunofluorescence staining and Western blotting [E-cadherin, vimentin, SNAIL/SLUG, AKT, phosphorylated (p)AKT, SMAD2/3 and pSMAD2/3] were performed after 72-h treatment. In silico analysis (molecular docking) of HT was performed to evaluate the potential of HT to bind with the TGFβ receptor. The viability of the HT-treated RECs was concentration-dependent, where the median effective concentration (EC50) was 19.04 μg/mL. Testing of the effects of 1 and 10 µg/mL HT revealed that HT suppressed expression of the protein markers vimentin and SNAIL/SLUG while preserving E-cadherin protein expression. Supplementation with HT protected against SMAD and AKT pathway activation in the TGFβ1-induced RECs. Furthermore, HT demonstrated the potential to bind with ALK5 (a TGFβ receptor component) in comparison to oleuropein. TGFβ1-induced EMT in RECs and HT exerted a positive effect in modulating the effects of EMT. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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17 pages, 3811 KiB  
Article
Antibacterial Aloe vera Based Biocompatible Hydrogel for Use in Dermatological Applications
by Mariana Chelu, Adina Magdalena Musuc, Ludmila Aricov, Emma Adriana Ozon, Andreea Iosageanu, Laura M. Stefan, Ana-Maria Prelipcean, Monica Popa and Jose Calderon Moreno
Int. J. Mol. Sci. 2023, 24(4), 3893; https://doi.org/10.3390/ijms24043893 - 15 Feb 2023
Cited by 11 | Viewed by 6089
Abstract
The present research aims to describe a new methodology to obtain biocompatible hydrogels based on Aloe vera used for wound healing applications. The properties of two hydrogels (differing in Aloe vera concentration, AV5 and AV10) prepared by an all-green synthesis method from raw, [...] Read more.
The present research aims to describe a new methodology to obtain biocompatible hydrogels based on Aloe vera used for wound healing applications. The properties of two hydrogels (differing in Aloe vera concentration, AV5 and AV10) prepared by an all-green synthesis method from raw, natural, renewable and bioavailable materials such as salicylic acid, allantoin and xanthan gum were investigated. The morphology of the Aloe vera based hydrogel biomaterials was studied by SEM analysis. The rheological properties of the hydrogels, as well as their cell viability, biocompatibility and cytotoxicity, were determined. The antibacterial activity of Aloe vera based hydrogels was evaluated both on Gram-positive, Staphylococcus aureus and on Gram-negative, Pseudomonas aeruginosa strains. The obtained novel green Aloe vera based hydrogels showed good antibacterial properties. In vitro scratch assay demonstrated the capacity of both AV5 and AV10 hydrogels to accelerate cell proliferation and migration and induce closure of a wounded area. A corroboration of all morphological, rheological, cytocompatibility and cell viability results indicates that this Aloe vera based hydrogel may be suitable for wound healing applications. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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20 pages, 5317 KiB  
Article
Antibacterial and Healing Effect of Chicha Gum Hydrogel (Sterculia striata) with Nerolidol
by Idglan Sá de Lima, Maria Onaira Gonçalves Ferreira, Esmeralda Maria Lustosa Barros, Marcia dos Santos Rizzo, Jailson de Araújo Santos, Alessandra Braga Ribeiro, Josy Anteveli Osajima Furtini, Edson C. Silva-Filho and Leticia M. Estevinho
Int. J. Mol. Sci. 2023, 24(3), 2210; https://doi.org/10.3390/ijms24032210 - 22 Jan 2023
Cited by 4 | Viewed by 1807
Abstract
Chicha gum is a natural polymer obtained from the Sterculia striata plant. The hydroxyl groups of its structure have a chemical affinity to form hydrogels, which favors the association with biologically active molecules, such as nerolidol. This association improves the biological properties and [...] Read more.
Chicha gum is a natural polymer obtained from the Sterculia striata plant. The hydroxyl groups of its structure have a chemical affinity to form hydrogels, which favors the association with biologically active molecules, such as nerolidol. This association improves the biological properties and allows the material to be used in drug delivery systems. Chicha gum hydrogels associated with nerolidol were produced at two concentrations: 0.01 and 0.02 g mL−1. Then, the hydrogels were characterized by thermogravimetry (TG), Fourier Transform Infrared spectroscopy (FTIR), and rheological analysis. The antibacterial activity was tested against Staphylococcus aureus and Escherichia coli. The cytotoxicity was evaluated against Artemia salina. Finally, an in vivo healing assay was carried out. The infrared characterization indicated that interactions were formed during the gel reticulation. This implies the presence of nerolidol in the regions at 3100–3550 cm−1. The rheological properties changed with an increasing concentration of nerolidol, which resulted in less viscous materials. An antibacterial 83.6% growth inhibition effect was observed using the hydrogel with 0.02 g mL−1 nerolidol. The in vivo healing assay showed the practical activity of the hydrogels in the wound treatment, as the materials promoted efficient re-epithelialization. Therefore, it was concluded that the chicha hydrogels have the potential to be used as wound-healing products. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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15 pages, 3034 KiB  
Article
Fabrication and Performance Evaluation of Gelatin/Sodium Alginate Hydrogel-Based Macrophage and MSC Cell-Encapsulated Paracrine System with Potential Application in Wound Healing
by Hang Yao, Xiaohui Yuan, Zhonglian Wu, Sumin Park, Wang Zhang, Hui Chong, Liwei Lin and Yuanzhe Piao
Int. J. Mol. Sci. 2023, 24(2), 1240; https://doi.org/10.3390/ijms24021240 - 08 Jan 2023
Cited by 13 | Viewed by 2333
Abstract
A gelatin/sodium alginate-based hydrogel microsphere has been fabricated after reaction condition optimization. Macrophages (RAW246.7) and adipose mesenchymal stem cells (ADSC) have been subsequently encapsulated in the microsphere in order to construct a 3D paracrine system for wound healing treatment. The synthesized microsphere displayed [...] Read more.
A gelatin/sodium alginate-based hydrogel microsphere has been fabricated after reaction condition optimization. Macrophages (RAW246.7) and adipose mesenchymal stem cells (ADSC) have been subsequently encapsulated in the microsphere in order to construct a 3D paracrine system for wound healing treatment. The synthesized microsphere displayed neglectable cytotoxicity toward both encapsulated cells until 10 days of incubation, indicating promising biocompatibility of the microsphere. A qRT-PCR and ELISA experiment revealed positive regulation of cytokines (Arg-1, IL-6, IL-8, IL-10, bFGF, HGF, VEGF, TLR-1, and CXCL13) expression regarding macrophage phenotype transformation and anti-inflammatory performance both inside the microsphere and in the microenvironment of established in vitro inflammatory model. Additionally, positive tendency of cytokine expression benefit wound healing was more pronounced in a fabricated 3D paracrine system than that of a 2D paracrine system. Furthermore, the 3D paracrine system exhibited more efficiently in the wound healing rate compared to the 2D paracrine system in an in vitro model. These results suggested the current paracrine system could be potentially used as a robust wound healing dressing. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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20 pages, 3914 KiB  
Article
The Antioxidant and In Vitro Wound Healing Activity of Cotyledon orbiculata Aqueous Extract and the Synthesized Biogenic Silver Nanoparticles
by Caroline Tyavambiza, Mervin Meyer, Adedoja Dorcas Wusu, Abram Madimabe Madiehe and Samantha Meyer
Int. J. Mol. Sci. 2022, 23(24), 16094; https://doi.org/10.3390/ijms232416094 - 17 Dec 2022
Cited by 3 | Viewed by 1853
Abstract
The synthesis of silver nanoparticles using biogenic methods, particularly plants, has led to the discovery of several effective nanoparticles. In many instances, plant-derived silver nanoparticles have been shown to have more activity than the plant extract which was used to synthesize the nanoparticles. [...] Read more.
The synthesis of silver nanoparticles using biogenic methods, particularly plants, has led to the discovery of several effective nanoparticles. In many instances, plant-derived silver nanoparticles have been shown to have more activity than the plant extract which was used to synthesize the nanoparticles. Silver nanoparticles have been successfully synthesized using the medicinal plant, Cotyledon orbiculata. This is a shrub found in the Western Cape province of South Africa. It has a long history of use in traditional medicine in the treatment of wounds and skin infections. The C. orbiculata synthesized silver nanoparticles (Cotyledon-AgNPs) were reported to have good antimicrobial and anti-inflammatory activities; however, their wound-healing properties have not been determined. This study aimed to determine the wound healing activity of Cotyledon-AgNPs using the scratch assay. Gene expression studies were also done to determine the nanoparticles’ mechanism of action. The Cotyledon-AgNPs showed good antioxidant, growth-promoting and cell migration properties. Gene expression studies showed that the C. orbiculata water extract and Cotyledon-AgNPs promoted wound healing by upregulating genes involved in cell proliferation, migration and growth while downregulating pro-inflammatory genes. This confirms, for the first time that a water extract of C. orbiculata and silver nanoparticles synthesized from this extract are good wound-healing agents. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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25 pages, 4262 KiB  
Article
Impact of Exosomes Released by Different Corneal Cell Types on the Wound Healing Properties of Human Corneal Epithelial Cells
by Pascale Desjardins, Rébecca Berthiaume, Camille Couture, Gaëtan Le-Bel, Vincent Roy, François Gros-Louis, Véronique J. Moulin, Stéphanie Proulx, Sylvain Chemtob, Lucie Germain and Sylvain L. Guérin
Int. J. Mol. Sci. 2022, 23(20), 12201; https://doi.org/10.3390/ijms232012201 - 13 Oct 2022
Cited by 6 | Viewed by 2014
Abstract
Corneal wound healing involves communication between the different cell types that constitute the three cellular layers of the cornea (epithelium, stroma and endothelium), a process ensured in part by a category of extracellular vesicles called exosomes. In the present study, we isolated exosomes [...] Read more.
Corneal wound healing involves communication between the different cell types that constitute the three cellular layers of the cornea (epithelium, stroma and endothelium), a process ensured in part by a category of extracellular vesicles called exosomes. In the present study, we isolated exosomes released by primary cultured human corneal epithelial cells (hCECs), corneal fibroblasts (hCFs) and corneal endothelial cells (hCEnCs) and determined whether they have wound healing characteristics of their own and to which point they modify the genetic and proteomic pattern of these cell types. Exosomes released by all three cell types significantly accelerated wound closure of scratch-wounded hCECs in vitro compared to controls (without exosomes). Profiling of activated kinases revealed that exosomes from human corneal cells caused the activation of signal transduction mediators that belong to the HSP27, STAT, β-catenin, GSK-3β and p38 pathways. Most of all, data from gene profiling analyses indicated that exosomes, irrespective of their cellular origin, alter a restricted subset of genes that are completely different between each targeted cell type (hCECs, hCFS, hCEnCs). Analysis of the genes specifically differentially regulated for a given cell-type in the microarray data using the Ingenuity Pathway Analysis (IPA) software revealed that the mean gene expression profile of hCECs cultured in the presence of exosomes would likely promote cell proliferation and migration whereas it would reduce differentiation when compared to control cells. Collectively, our findings represent a conceptual advance in understanding the mechanisms of corneal wound repair that may ultimately open new avenues for the development of novel therapeutic approaches to improve closure of corneal wounds. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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8 pages, 1173 KiB  
Communication
A Preliminary Direct Comparison of the Inflammatory Reduction and Growth Factor Production Capabilities of Three Commercially Available Wound Products: Collagen Sheet, Manuka Honey Sheet, and a Novel Bioengineered Collagen Derivative + Manuka Honey + Hydroxyapatite Sheet
by Isaac Rodriguez, Tricia Conti and Nina Bionda
Int. J. Mol. Sci. 2022, 23(18), 10670; https://doi.org/10.3390/ijms231810670 - 14 Sep 2022
Cited by 1 | Viewed by 2479
Abstract
Many commercially available wound products focus on improving one stage of the wound healing cascade. While this targeted approach works for specific wounds, there is a need for products that can reliably and comprehensively progress a wound through multiple stages. This preliminary in [...] Read more.
Many commercially available wound products focus on improving one stage of the wound healing cascade. While this targeted approach works for specific wounds, there is a need for products that can reliably and comprehensively progress a wound through multiple stages. This preliminary in vitro study was performed to directly compare the inflammatory reduction and growth factor production effects of three commercially available wound care products: a collagen sheet (COL), a Manuka Honey Calcium Alginate sheet (MH), and a novel bioengineered sheet comprised of a collagen derivative (gelatin), Manuka honey, and hydroxyapatite (BCMH). Macrophages and human dermal fibroblasts were directly seeded on all three commercial products, and supernatants were analyzed for inflammatory markers and growth factors, respectively. Comparing the MMP-9/TIMP-1 ratio, BCMH resulted in 11× lower levels of this inflammation biomarker compared to COL, and 3× lower levels compared to MH. Both the COL and BCMH products created an environment conducive to expression and release of relevant growth factors, while the MH product showed the lowest levels of growth factor expression of all three commercially available products tested. The favorable 11× lower MMP-9/TIMP-1 ratio observed with the BCMH product compared to the COL product suggests that the BCMH products provided a superior comprehensive approach to healthy progression of the wounds by providing an additional benefit of reducing the inflammatory response in vitro. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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16 pages, 3812 KiB  
Article
Evaluation of Platelet-Derived Extracellular Vesicles in Gingival Fibroblasts and Keratinocytes for Periodontal Applications
by Miquel Antich-Rosselló, Marta Munar-Bestard, Maria Antònia Forteza-Genestra, Javier Calvo, Antoni Gayà, Marta Monjo and Joana M. Ramis
Int. J. Mol. Sci. 2022, 23(14), 7668; https://doi.org/10.3390/ijms23147668 - 11 Jul 2022
Cited by 7 | Viewed by 2035
Abstract
Gingival regeneration aims at restoring the architecture and functionality of oral damaged tissue. Different biomaterials or biological materials have been tested for tissue repair, such as platelet concentrates such as PL. In this article, the use of extracellular vesicles (EVs) derived from platelet [...] Read more.
Gingival regeneration aims at restoring the architecture and functionality of oral damaged tissue. Different biomaterials or biological materials have been tested for tissue repair, such as platelet concentrates such as PL. In this article, the use of extracellular vesicles (EVs) derived from platelet lysate (PL) and their combination with hyaluronic acid biomaterials (HA) in an in vitro wound healing assay is investigated. EVs were isolated by size exclusion chromatography from PL. In addition, HA gels were formulated with PL or EVs. EVs or HA combined with EVs (HA-EVs) were tested in vitro in gingival fibroblasts and keratinocytes for biocompatibility (LDH activity and metabolic activity) and by an in vitro wound-healing assay and gene expression analysis. EVs and EVs-HA treatments were biocompatible in gingival fibroblasts and keratinocytes and showed an increase in wound healing in vitro compared to control. Moreover, changes in gene expression related to extracellular matrix remodeling were observed after the treatment with EVs. EVs can be combined with HA biomaterials, showing good biocompatibility and preserving their activity and functionality. Therefore, platelet-derived EVs could emerge as a new application for periodontal regeneration in combination with biomaterials in order to enhance their clinical use. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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Review

Jump to: Research

25 pages, 3794 KiB  
Review
Chitosan-Based Biomaterials for Hemostatic Applications: A Review of Recent Advances
by Daniela Gheorghiță, Horațiu Moldovan, Alina Robu, Ana-Iulia Bița, Elena Grosu, Aurora Antoniac, Iuliana Corneschi, Iulian Antoniac, Alin Dănuț Bodog and Ciprian Ionuț Băcilă
Int. J. Mol. Sci. 2023, 24(13), 10540; https://doi.org/10.3390/ijms241310540 - 23 Jun 2023
Cited by 8 | Viewed by 3256
Abstract
Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and [...] Read more.
Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and decrease the risk of morbidity and mortality associated with hemorrhage, it is necessary to use an effective hemostatic agent that ensures the immediate control of bleeding. In recent years, there have been increasingly rapid advances in developing a novel generation of biomaterials with hemostatic properties. Nowadays, a wide array of topical hemostatic agents is available, including chitosan-based biomaterials that have shown outstanding properties such as antibacterial, antifungal, hemostatic, and analgesic activity in addition to their biocompatibility, biodegradability, and wound-healing effects. This review provides an analysis of chitosan-based hemostatic biomaterials and discusses the progress made in their performance, mechanism of action, efficacy, cost, and safety in recent years. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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34 pages, 1640 KiB  
Review
Anti-Glucotoxicity Effect of Phytoconstituents via Inhibiting MGO-AGEs Formation and Breaking MGO-AGEs
by Neera Yadav, Jyoti Dnyaneshwar Palkhede and Sun-Yeou Kim
Int. J. Mol. Sci. 2023, 24(8), 7672; https://doi.org/10.3390/ijms24087672 - 21 Apr 2023
Cited by 3 | Viewed by 2349
Abstract
The therapeutic benefits of phytochemicals in the treatment of various illnesses and disorders are well documented. They show significant promise for the discovery and creation of novel medications for treating a variety of human diseases. Numerous phytoconstituents have shown antibiotic, antioxidant, and wound-healing [...] Read more.
The therapeutic benefits of phytochemicals in the treatment of various illnesses and disorders are well documented. They show significant promise for the discovery and creation of novel medications for treating a variety of human diseases. Numerous phytoconstituents have shown antibiotic, antioxidant, and wound-healing effects in the conventional system. Traditional medicines based on alkaloids, phenolics, tannins, saponins, terpenes, steroids, flavonoids, glycosides, and phytosterols have been in use for a long time and are crucial as alternative treatments. These phytochemical elements are crucial for scavenging free radicals, capturing reactive carbonyl species, changing protein glycation sites, inactivating carbohydrate hydrolases, fighting pathological conditions, and accelerating the healing of wounds. In this review, 221 research papers have been reviewed. This research sought to provide an update on the types and methods of formation of methylglyoxal-advanced glycation end products (MGO-AGEs) and molecular pathways induced by AGEs during the progression of the chronic complications of diabetes and associated diseases as well as to discuss the role of phytoconstituents in MGO scavenging and AGEs breaking. The development and commercialization of functional foods using these natural compounds can provide potential health benefits. Full article
(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration)
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