Regulation of Wound Healing by Growth Factors and Cytokines

Werner, Sabine, and Richard Grose. Regulation of Wound Healing by Growth Factors and Cytokines. Physiol Rev 83: 835–870, 2003; 10.1152/physrev.00032.2002.—Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors have remained largely unclear. Initial approaches at addressing this question focused on the expression analysis of various growth factors, cytokines, and their receptors in different wound models, with first functional data being obtained by applying neutralizing antibodies to wounds. During the past few years, the availability of genetically modified mice has allowed elucidation of the function of various genes in the healing process, and these studies have shed light onto the role of growth factors, cytokines, and their downstream effectors in wound repair. This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds. Most importantly, we also report on genetic studies addressing the functions of endogenous growth factors in the wound repair process.

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The Role of the Extracellular Matrix Components in Cutaneous Wound Healing

BioMed Research International ◽

10.1155/2014/747584 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 113

Author(s):

Pawel Olczyk ◽

Łukasz Mencner ◽

Katarzyna Komosinska-Vassev

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Growth Factors ◽

Wound Repair ◽

Structural Integrity ◽

Healing Process ◽

Cellular Functions ◽

Extracellular Matrix Components ◽

Essential Components ◽

Matrix Components

Wound healing is the physiologic response to tissue trauma proceeding as a complex pathway of biochemical reactions and cellular events, secreted growth factors, and cytokines. Extracellular matrix constituents are essential components of the wound repair phenomenon. Firstly, they create a provisional matrix, providing a structural integrity of matrix during each stage of healing process. Secondly, matrix molecules regulate cellular functions, mediate the cell-cell and cell-matrix interactions, and serve as a reservoir and modulator of cytokines and growth factors’ action. Currently known mechanisms, by which extracellular matrix components modulate each stage of the process of soft tissue remodeling after injury, have been discussed.

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TERAPI LARVA PADA LUKA KRONIS TERBUKA

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.7.1.2015.7289 ◽

2015 ◽

Vol 7 (1) ◽

Author(s):

Sunny Wangko

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Chronic Wound ◽

Healing Process ◽

Bioactive Molecules ◽

Wound Management ◽

Wound Healing Process ◽

Beneficial Effects ◽

Infected Wounds ◽

Larval Therapy

Abstract: The usage of larvae in wound treatment has been known across the centuries in different countries. However, larval therapy is offered when the conventional therapy has failed in the management of chronic, infected wounds. Concerning the larval therapy, it was presumed that the wound healing was due to the mechanical debridement effect of the larval movement and of their hooks. To date, a variety of study reports reveals that there are several beneficial effects of the larval therapy, inter alia: secretion/excretion of larvae contains enzymes, growth factors, and cytokines that collaborate in the wound healing process. The bioactive molecules in the secretion/excretion of the larvae has to be further studied and to be developed, therefore, they can be applied in the wound management efficiently and economically. Keywords: larval therapy, chronic wound, healing process. Abstrak: Walaupun pemanfaatan larva pada luka kronis telah sangat lama dikenal di berbagai negara, terapi larva umumnya digunakan bila terapi konvensional telah gagal. Awalnya diduga bahwa efek debridemen mekanis oleh gerakan larva dan kaitnya yang paling berperan. Dewasa ini, laporan berbagi studi telah mengungkapkan bahwa larva menyekresi dan menyintesis berbagai bahan baik berupa enzim, sitokin, dan growth factors yang turut berperan dalam proses penyembuhan luka. Adanya molekul bioaktif dalam ekskresi dan sekresi larva perlu diteliti dan dikembangkan agar dapat diaplikasikan dengan lebih efisien dan ekonomis. Kata kunci: terapi larva, luka kronis, penyembuhan luka.

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Role of Growth Factors in Cutaneous Wound Healing: A Review

Critical Reviews in Oral Biology & Medicine ◽

10.1177/10454411930040050401 ◽

1993 ◽

Vol 4 (5) ◽

pp. 729-760 ◽

Cited By ~ 120

Author(s):

Christopher P. Kiritsy ◽

Samuel E. Lynch

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Healing Process ◽

Repair Process ◽

Wound Healing Process ◽

Cutaneous Wounds ◽

Skin Ulcers ◽

Molecular Events ◽

Chronic Skin ◽

Preclinical Animal Models

The well-orchestrated, complex series of events resulting in the repair of cutaneous wounds are, at least in part, regulated by polypeptide growth factors. This review provides a detailed overview of the known functions, interactions, and mechanisms of action of growth factors in the context of the overall repair process in cutaneous wounds. An overview of the cellular and molecular events involved in soft tissue repair is initially presented, followed by a review of widely studied growth factors and a discussion of commonly utilized preclinical animal models. The article concludes with a summary of the preliminary results from human clinical trials evaluating the effects of growth factors in the healing of chronic skin ulcers. Throughout, the interactions among the growth factors in the wound-healing process are emphasized.

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The Role of MSC in Wound Healing, Scarring and Regeneration

Cells ◽

10.3390/cells10071729 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1729

Author(s):

Raquel Guillamat-Prats

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Therapeutic Potential ◽

Healing Process ◽

Repair Process ◽

Skin Wound ◽

Wound Healing Process ◽

Matrix Remodeling ◽

Skin Wound Healing ◽

Tissue Repair And Regeneration

Tissue repair and regeneration after damage is not completely understood, and current therapies to support this process are limited. The wound healing process is associated with cell migration and proliferation, extracellular matrix remodeling, angiogenesis and re-epithelialization. In normal conditions, a wound will lead to healing, resulting in reparation of the tissue. Several risk factors, chronic inflammation, and some diseases lead to a deficient wound closure, producing a scar that can finish with a pathological fibrosis. Mesenchymal stem/stromal cells (MSCs) are widely used for their regenerative capacity and their possible therapeutically potential. Derived products of MSCs, such as exosomes or extravesicles, have shown a therapeutic potential similar to MSCs, and these cell-free products may be interesting in clinics. MSCs or their derivative products have shown paracrine beneficial effects, regulating inflammation, modifying the fibroblast activation and production of collagen and promoting neovascularization and re-epithelialization. This review describes the effects of MSCs and their derived products in each step of the wound repair process. As well, it reviews the pre-clinical and clinical use of MSCs to benefit in skin wound healing in diabetic associated wounds and in pathophysiological fibrosis.

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Mesenchymal Stromal Cells as Cell-Based Therapeutics for Wound Healing

Stem Cells International ◽

10.1155/2016/4157934 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 18

Author(s):

Samir Malhotra ◽

Michael S. Hu ◽

Clement D. Marshall ◽

Tripp Leavitt ◽

Alexander T. M. Cheung ◽

...

Keyword(s):

Wound Healing ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Wound Repair ◽

Chronic Wounds ◽

Financial Burden ◽

Healing Process ◽

Repair Process ◽

Wound Healing Process ◽

Promising Source

Chronic wounds are a source of substantial morbidity for patients and are a major financial burden for the healthcare system. There are no current therapies that reliably improve nonhealing wounds or reverse pathological scarring. Mesenchymal stromal cells (MSCs) are a promising source of novel cell-based therapies due to the ease of their harvest and their integral role in the native wound repair process. Recent work has addressed the problems of loss of plasticity and off-target delivery through use of modern bioengineering techniques. Here we describe the applications of MSCs harvested from different sources to the wound healing process and recent advances in delivery of MSCs to targeted sites of injury.

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Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration

Pharmaceutics ◽

10.3390/pharmaceutics12080735 ◽

2020 ◽

Vol 12 (8) ◽

pp. 735 ◽

Cited By ~ 7

Author(s):

Erika Maria Tottoli ◽

Rossella Dorati ◽

Ida Genta ◽

Enrica Chiesa ◽

Silvia Pisani ◽

...

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Wound Repair ◽

Chronic Wounds ◽

Healing Process ◽

Skin Wound ◽

Skin Regeneration ◽

Bioactive Molecules ◽

Wound Healing Process ◽

Skin Wound Healing

Skin wound healing shows an extraordinary cellular function mechanism, unique in nature and involving the interaction of several cells, growth factors and cytokines. Physiological wound healing restores tissue integrity, but in many cases the process is limited to wound repair. Ongoing studies aim to obtain more effective wound therapies with the intention of reducing inpatient costs, providing long-term relief and effective scar healing. The main goal of this comprehensive review is to focus on the progress in wound medication and how it has evolved over the years. The main complications related to the healing process and the clinical management of chronic wounds are described in the review. Moreover, advanced treatment strategies for skin regeneration and experimental techniques for cellular engineering and skin tissue engineering are addressed. Emerging skin regeneration techniques involving scaffolds activated with growth factors, bioactive molecules and genetically modified cells are exploited to overcome wound healing technology limitations and to implement personalized therapy design.

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Natural, Synthetic and their Combinatorial Nanocarriers Based Drug Delivery System in the Treatment Paradigm for Wound Healing Via Dermal Targeting

Current Pharmaceutical Design ◽

10.2174/1381612826666200612164511 ◽

2020 ◽

Vol 26 (36) ◽

pp. 4551-4568

Author(s):

Mohammad Kashif Iqubal ◽

Sadaf Saleem ◽

Ashif Iqubal ◽

Aiswarya Chaudhuri ◽

Faheem Hyder Pottoo ◽

...

Keyword(s):

Drug Delivery ◽

Wound Healing ◽

Photodynamic Therapy ◽

Growth Factors ◽

Combination Therapy ◽

Healing Process ◽

Wound Healing Process ◽

Wound Site ◽

Synthetic Drugs ◽

Treatment Paradigm

A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional integrity of the damaged tissues. This process is mediated by various cytokines and growth factors usually liberated at the wound site. A plethora of herbal and synthetic drugs, as well as photodynamic therapy, is available to facilitate the process of wound healing. Generally, the systems used for the management of wounds tend to act through covering the ruptured site, reduce pain, inflammation, and prevent the invasion and growth of microorganisms. The available systems are, though, enough to meet these requirements, but the involvement of nanotechnology can ameliorate the performance of these protective coverings. In recent years, nano-based formulations have gained immense popularity among researchers for the wound healing process due to the enhanced benefits they offer over the conventional preparations. Hereupon, this review aims to cover the entire roadmap of wound healing, beginning from the molecular factors involved in the process, the various synthetic and herbal agents, and combination therapy available for the treatment and the current nano-based systems available for delivery through the topical route for wound healing.

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Multi-Functional Core-Shell Nanofibers for Wound Healing

Nanomaterials ◽

10.3390/nano11061546 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1546

Author(s):

Zhen Li ◽

Shunqi Mei ◽

Yajie Dong ◽

Fenghua She ◽

Puwang Li ◽

...

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Drug Release ◽

Release Rate ◽

Healing Process ◽

Wound Healing Process ◽

Core Shell ◽

High Production Rate ◽

Centrifugal Spinning ◽

Multiple Drugs

Core-shell nanofibers have great potential for bio-medical applications such as wound healing dressings where multiple drugs and growth factors are expected to be delivered at different healing phases. Compared to monoaxial nanofibers, core-shell nanofibers can control the drug release profile easier, providing sustainable and effective drugs and growth factors for wound healing. However, it is challenging to produce core-shell structured nanofibers with a high production rate at low energy consumption. Co-axial centrifugal spinning is an alternative method to address the above limitations to produce core-shell nanofibers effectively. In this study, a co-axial centrifugal spinning device was designed and assembled to produce core-shell nanofibers for controlling the release rate of ibuprofen and hEGF in inflammation and proliferation phases during the wound healing process. Core-shell structured nanofibers were confirmed by TEM. This work demonstrated that the co-axial centrifugal spinning is a high productivity process that can produce materials with a 3D environment mimicking natural tissue scaffold, and the specific drug can be loaded into different layers to control the drug release rate to improve the drug efficiency and promote wound healing.

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Topical Saudi Arabia Talh honey (Acacia nilotica) on surgical wound healing activity

Highlights in BioScience ◽

10.36462/h.biosci.20220 ◽

2020 ◽

Author(s):

Ahmed G. Hegazi ◽

Faiz M. Al Guthami ◽

Mohamed H. Basiouny ◽

Ahmed F.M. Al Gethami

Keyword(s):

Wound Healing ◽

Saudi Arabia ◽

Wound Repair ◽

Healing Process ◽

Bacterial Count ◽

Tissue Growth ◽

Acacia Nilotica ◽

Total Bacterial Count ◽

Wound Healing Process ◽

Ifn Γ

Honey has been documented as the oldest traditional medicine. It has been effective in suppressing inflammation, wound repair enhancer, and rapid autolytic debridement. The aim of this investigation was to evaluate the role of Saudi Arabia Talh honey (Acacia nilotica) dressing as a good alternative in care of diabetic foot (DFU) healing activity for twenty patients, wound total bacterial count, and serum cytokines levels (IFN-γ, IL-1, and IL-6). The results showed that Talh honey stimulates the wound healing process, broad-spectrum antibacterial activity, and reduction in the proinflammatory cytokines IFN-γ, IL-1, and IL-6 levels. It could be concluded that Talh honey bioactivities enhance wound healing by promoting tissue growth leading to wound repair, antibacterial, and reduction of inflammation.

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Systemic and topical administration of spermidine accelerates skin wound healing

10.21203/rs.3.rs-111107/v1 ◽

2020 ◽

Author(s):

Daisuke Ito ◽

Hiroyasu Ito ◽

Takayasu Ideta ◽

Ayumu Kanbe ◽

Soranobu Ninomiya ◽

...

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Wound Repair ◽

Healing Process ◽

Topical Administration ◽

Skin Wound ◽

Wound Healing Process ◽

Skin Wound Healing

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

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