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20 pages, 3322 KiB

Open AccessArticle

Effect of Polymeric Nanoparticles with Entrapped Fish Oil or Mupirocin on Skin Wound Healing Using a Porcine Model

by Tomáš Komprda, Zbyšek Sládek, Monika Vícenová, Jana Simonová, Gabriela Franke, Břetislav Lipový, Milena Matejovičová, Katarína Kacvinská, Cristina Sabliov, Carlos E. Astete, Lenka Levá, Vendula Popelková, Andrej Bátik and Lucy Vojtová

Int. J. Mol. Sci. 2022, 23(14), 7663; https://doi.org/10.3390/ijms23147663 - 11 Jul 2022

Cited by 3 | Viewed by 2144

Abstract

The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 × 5 cm) on the pig dorsa were [...] Read more.

The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 × 5 cm) on the pig dorsa were treated with pure collagen scaffold (control, C), empty PLGA NPs (NP), FO, mupirocin (MUP), PLGA NPs with entrapped FO (NP/FO) and PLGA NPs with entrapped MUP (NP/MUP). The following markers were evaluated on days 0, 3, 7, 14 and 21 post-excision: collagen, hydroxyproline (HP), angiogenesis and expressions of the COX2, EGF, COL1A1, COL1A3, TGFB1, VEGFA, CCL5 and CCR5 genes. The hypothesis that NP/FO treatment is superior to FO alone and that it is comparable to NP/MUP was tested. NP/FO treatment increased HP in comparison with both FO alone and NP/MUP (day 14) but decreased (p < 0.05) angiogenesis in comparison with FO alone (day 3). NP/FO increased (p < 0.05) the expression of the CCR5 gene (day 3) and tended (p > 0.05) to increase the expressions of the EGF (day 7, day 14), TGFB1 (day 21) and CCL5 (day 7, day 21) genes as compared with NP/MUP. NP/FO can be suggested as a suitable alternative to NP/MUP in cutaneous wound treatment. Full article

(This article belongs to the Special Issue Focus on Wound Healing)

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11 pages, 7417 KiB

Open AccessArticle

Fibroblast Growth Factor 7 Suppresses Fibrosis and Promotes Epithelialization during Wound Healing in Mouse Fetuses

by Kento Takaya, Noriko Aramaki-Hattori, Shigeki Sakai, Keisuke Okabe, Toru Asou and Kazuo Kishi

Int. J. Mol. Sci. 2022, 23(13), 7087; https://doi.org/10.3390/ijms23137087 - 25 Jun 2022

Cited by 10 | Viewed by 2152

Abstract

Adult mammalian wounds leave visible scars, whereas skin wounds in developing mouse fetuses are scarless until a certain point in development when complete regeneration occurs, including the structure of the dermis and skin appendages. Analysis of the molecular mechanisms at this transition will [...] Read more.

Adult mammalian wounds leave visible scars, whereas skin wounds in developing mouse fetuses are scarless until a certain point in development when complete regeneration occurs, including the structure of the dermis and skin appendages. Analysis of the molecular mechanisms at this transition will provide clues for achieving scarless wound healing. The fibroblast growth factor (FGF) family is a key regulator of inflammation and fibrosis during wound healing. We aimed to determine the expression and role of FGF family members in fetal wound healing. ICR mouse fetuses were surgically wounded at embryonic day 13 (E13), E15, and E17. Expression of FGF family members and FGF receptor (FGFR) in tissue samples from these fetuses was evaluated using in situ hybridization and reverse transcription-quantitative polymerase chain reaction. Fgfr1 was downregulated in E15 and E17 wounds, and its ligand Fgf7 was upregulated in E13 and downregulated in E15 and E17. Recombinant FGF7 administration in E15 wounds suppressed fibrosis and promoted epithelialization at the wound site. Therefore, the expression level of Fgf7 may correlate with scar formation in late mouse embryos, and external administration of FGF7 may represent a therapeutic option to suppress fibrosis and reduce scarring. Full article

(This article belongs to the Special Issue Focus on Wound Healing)

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Review

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26 pages, 2144 KiB

Open AccessReview

Wound Healing Impairment in Type 2 Diabetes Model of Leptin-Deficient Mice—A Mechanistic Systematic Review

by Albert Stachura, Ishani Khanna, Piotr Krysiak, Wiktor Paskal and Paweł Włodarski

Int. J. Mol. Sci. 2022, 23(15), 8621; https://doi.org/10.3390/ijms23158621 - 03 Aug 2022

Cited by 14 | Viewed by 3363

Abstract

Type II diabetes mellitus (T2DM) is one of the most prevalent diseases in the world, associated with diabetic foot ulcers and impaired wound healing. There is an ongoing need for interventions effective in treating these two problems. Pre-clinical studies in this field rely [...] Read more.

Type II diabetes mellitus (T2DM) is one of the most prevalent diseases in the world, associated with diabetic foot ulcers and impaired wound healing. There is an ongoing need for interventions effective in treating these two problems. Pre-clinical studies in this field rely on adequate animal models. However, producing such a model is near-impossible given the complex and multifactorial pathogenesis of T2DM. A leptin-deficient murine model was developed in 1959 and relies on either dysfunctional leptin (ob/ob) or a leptin receptor (db/db). Though monogenic, this model has been used in hundreds of studies, including diabetic wound healing research. In this study, we systematically summarize data from over one hundred studies, which described the mechanisms underlying wound healing impairment in this model. We briefly review the wound healing dynamics, growth factors’ dysregulation, angiogenesis, inflammation, the function of leptin and insulin, the role of advanced glycation end-products, extracellular matrix abnormalities, stem cells’ dysregulation, and the role of non-coding RNAs. Some studies investigated novel chronic diabetes wound models, based on a leptin-deficient murine model, which was also described. We also discussed the interventions studied in vivo, which passed into human clinical trials. It is our hope that this review will help plan future research. Full article

(This article belongs to the Special Issue Focus on Wound Healing)

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15 pages, 825 KiB

Open AccessReview

Platelet Derivatives and the Immunomodulation of Wound Healing

by Fernanda Scopelliti, Caterina Cattani, Valentina Dimartino, Concetta Mirisola and Andrea Cavani

Int. J. Mol. Sci. 2022, 23(15), 8370; https://doi.org/10.3390/ijms23158370 - 28 Jul 2022

Cited by 20 | Viewed by 3176

Abstract

Besides their primary role in hemostasis, platelets contain a plethora of immunomodulatory molecules that profoundly affect the entire process of wound repair. Therefore, platelet derivatives, such as platelet-rich plasma or platelet lysate, have been widely employed with promising results in the treatment of [...] Read more.

Besides their primary role in hemostasis, platelets contain a plethora of immunomodulatory molecules that profoundly affect the entire process of wound repair. Therefore, platelet derivatives, such as platelet-rich plasma or platelet lysate, have been widely employed with promising results in the treatment of chronic wounds. Platelet derivatives provide growth factors, cytokines, and chemokines targeting resident and immigrated cells belonging to the innate and adaptive immune system. The recruitment and activation of neutrophils and macrophages is critical for pathogen clearance in the early phase of wound repair. The inflammatory response begins with the release of cytokines, such as TGF-β, aimed at damping excessive inflammation and promoting the regenerative phase of wound healing. Dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wound. In this review, we summarize the role of the different immune cells involved in wound healing, particularly emphasizing the function of platelet and platelet derivatives in orchestrating the immunological response. Full article

(This article belongs to the Special Issue Focus on Wound Healing)

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21 pages, 1737 KiB

Open AccessReview

The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model

by Mateusz Mieczkowski, Beata Mrozikiewicz-Rakowska, Michał Kowara, Marcin Kleibert and Leszek Czupryniak

Int. J. Mol. Sci. 2022, 23(14), 7930; https://doi.org/10.3390/ijms23147930 - 19 Jul 2022

Cited by 16 | Viewed by 4717

Abstract

Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects [...] Read more.

Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects in whom the healing process is particularly prolonged regardless of its initial etiology. Circulatory dysfunction, both at the microvascular and macrovascular levels, is a leading factor in delaying or precluding wound healing in diabetes. The prolonged period of wound healing increases the risk of complications such as the development of infection, including sepsis and even amputation. Currently, many substances applied topically or systemically are supposed to accelerate the process of wound regeneration and finally wound closure. The role of clinical trials and preclinical studies, including research based on animal models, is to create safe medicinal products and ensure the fastest possible healing. To achieve this goal and minimize the wide-ranging burdens associated with conducting clinical trials, a correct animal model is needed to replicate the wound conditions in patients with diabetes as closely as possible. The aim of the paper is to summarize the most important molecular pathways which are impaired in the hyperglycemic state in the context of designing an animal model of diabetic chronic wounds. The authors focus on research optimization, including economic aspects and model reproducibility, as well as the ethical dimension of minimizing the suffering of research subjects according to the 3 Rs principle (Replacement, Reduction, Refinement). Full article

(This article belongs to the Special Issue Focus on Wound Healing)

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11 pages, 1050 KiB

Open AccessReview

Fine Regulation during Wound Healing by Mast Cells, a Physiological Role Not Yet Clarified

by Stefano Bacci

Int. J. Mol. Sci. 2022, 23(3), 1820; https://doi.org/10.3390/ijms23031820 - 05 Feb 2022

Cited by 25 | Viewed by 3021

Abstract

Mast cells (MCs) are bone marrow-derived cells capable of secreting many active molecules, ranging from the mediators stored in specific granules, some of which have been known about for several decades (histamine, heparin), to small molecules produced immediately upon stimulation (membrane lipid derivatives, [...] Read more.

Mast cells (MCs) are bone marrow-derived cells capable of secreting many active molecules, ranging from the mediators stored in specific granules, some of which have been known about for several decades (histamine, heparin), to small molecules produced immediately upon stimulation (membrane lipid derivatives, nitric oxide), to a host of constitutively secreted, multifunctional cytokines. With the aid of a wide array of mediators, the activated MCs control the key events of inflammation and therefore participate in the regulation of local immune response. On the basis of the structure, origin, principal subtypes, localization and function of these cells, their involvement in injury repair is therefore to be considered in acute and chronic conditions, respectively. The importance of MCs in regulating the healing processes is underscored by the proposed roles of a surplus or a deficit of their mediators in the formation of exuberant granulation tissue (such as keloids and hypertrophic scars), the delayed closure or dehiscence of wounds and the transition of acute to chronic inflammation. Full article

(This article belongs to the Special Issue Focus on Wound Healing)

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14 pages, 556 KiB

Open AccessReview

The Regenerative Potential of Substance P

by Patrycja Redkiewicz

Int. J. Mol. Sci. 2022, 23(2), 750; https://doi.org/10.3390/ijms23020750 - 11 Jan 2022

Cited by 9 | Viewed by 2575

Abstract

Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous insufficiencies or autoimmune diseases could disturb proper wound healing and lead to chronic and non-healing wounds, which are still [...] Read more.

Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous insufficiencies or autoimmune diseases could disturb proper wound healing and lead to chronic and non-healing wounds, which are still a great challenge for medicine. For many years, research has been carried out on finding new therapeutics which improve the healing of chronic wounds. One of the most extensively studied active substances that has been widely tested in the treatment of different types of wounds was Substance P (SP). SP is one of the main neuropeptides released by nervous fibers in responses to injury. This review provides a thorough overview of the application of SP in different types of wound models and assesses its efficacy in wound healing. Full article

(This article belongs to the Special Issue Focus on Wound Healing)

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18 pages, 2264 KiB

Open AccessReview

The Role of the Inflammatory Response in Mediating Functional Recovery Following Composite Tissue Injuries

by Naveena B. Janakiram, Michael S. Valerio, Stephen M. Goldman and Christopher L. Dearth

Int. J. Mol. Sci. 2021, 22(24), 13552; https://doi.org/10.3390/ijms222413552 - 17 Dec 2021

Cited by 10 | Viewed by 4094

Abstract

Composite tissue injuries (CTI) are common among US Military Service members during combat operations, and carry a high potential of morbidity. Furthermore, CTI are often complicated due to an altered wound healing response, resulting in part from a dysregulation of the innate and [...] Read more.

Composite tissue injuries (CTI) are common among US Military Service members during combat operations, and carry a high potential of morbidity. Furthermore, CTI are often complicated due to an altered wound healing response, resulting in part from a dysregulation of the innate and adaptive immune responses. Unlike normal wound healing, in CTI, disruptions occur in innate immune responses, altering neutrophil functions, macrophage activation and polarization, further impacting the functions of T regulatory cells. Additionally, the biological underpinnings of these unfavorable wound healing conditions are multifactorial, including various processes, such as: ischemia, hypoxia, low nutrient levels, and altered cell metabolic pathways, among others, all of which are thought to trigger anergy in immune cells and destabilize adaptive immune responses. As a result, impaired wound healing is common in CTI. Herein, we review the altered innate and adaptive immune cells and their metabolic status and responses following CTI, and discuss the role a multi-pronged immunomodulatory approach may play in facilitating improved outcomes for afflicted patients. Full article

(This article belongs to the Special Issue Focus on Wound Healing)

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