scholarly journals Endothelial Response Boosted by Platelet Lysate: The Involvement of Calcium Toolkit

2020 ◽  
Vol 21 (3) ◽  
pp. 808
Author(s):  
Simona Martinotti ◽  
Mauro Patrone ◽  
Valeria Balbo ◽  
Laura Mazzucco ◽  
Elia Ranzato

Wound repair is a dynamic process during which crucial signaling pathways are regulated by growth factors and cytokines released by several kinds of cells directly involved in the healing process. However, the limited applications and heterogeneous clinical results of single growth factors in wound healing encouraged the use of a mixture of bioactive molecules such as platelet derivatives for best results in wound repair. An interesting platelet derivative, obtained from blood samples, is platelet lysate (PL), which has shown potential clinical application. PL is obtained from freezing and thawing of platelet-enriched blood samples. Intracellular calcium (Ca2+) signals play a central role in the control of endothelial cell survival, proliferation, motility, and differentiation. We investigated the role of Ca2+ signaling in the PL-driven endothelial healing process. In our experiments, the functional significance of Ca2+ signaling machinery was highlighted performing the scratch wound assay in presence of different inhibitors or specific RNAi. We also pointed out that the PL-induced generation of intracellular ROS (reactive oxygen species) via NOX4 (NADPH oxidase 4) is necessary for the activation of TRPM2 and the resulting Ca2+ entry from the extracellular space. This is the first report of the mechanism of wound repair in an endothelial cell model boosted by the PL-induced regulation of [Ca2+]i.

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 735 ◽  
Author(s):  
Erika Maria Tottoli ◽  
Rossella Dorati ◽  
Ida Genta ◽  
Enrica Chiesa ◽  
Silvia Pisani ◽  
...  

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pawel Olczyk ◽  
Łukasz Mencner ◽  
Katarzyna Komosinska-Vassev

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.


2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Sunny Wangko

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.


1999 ◽  
Vol 276 (4) ◽  
pp. E663-E671 ◽  
Author(s):  
J. Gray Robertson ◽  
David A. Belford ◽  
F. John Ballard

We have examined the role binding proteins have in regulating the clearance of exogenous growth factors from wounds. Hunt-Schilling chambers were subcutaneously implanted in rats, and the clearance of insulin-like growth factor (IGF) I from the chamber wound fluid was compared with IGF-II, LR3-IGF-I, which binds poorly to IGF-binding proteins (IGFBP), or insulin. Elimination rate constants of the slow phase of the decay curves did not differ between IGF-I and IGF-II. However, LR3-IGF-I and insulin were cleared more rapidly from wound fluid than IGF-I so that the half-lives for IGF-I, IGF-II, LR3-IGF-I, and insulin were 872, 861, 563, and 324 min, respectively. In wound fluid, minimal degradation of the IGFs occurred, whereas insulin was degraded considerably. The increased clearance of LR3-IGF-I and insulin equated with a reduced association with wound fluid IGFBPs, and increased amounts of radioactivity of these peptides were detected in the circulation and urine. These results show that this model of wound repair may be of use in examining the kinetics of growth factors and other bioactive molecules in extravascular spaces and support the hypothesis that IGFBPs can be significant regulators of IGF bioavailability in vivo.


Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 995
Author(s):  
Elena Filova ◽  
Andreu Blanquer ◽  
Jarmila Knitlova ◽  
Martin Plencner ◽  
Vera Jencova ◽  
...  

Platelet lysate (PL) provides a natural source of growth factors and other bioactive molecules, and the local controlled release of these bioactive PL components is capable of improving the healing of chronic wounds. Therefore, we prepared composite nanofibrous meshes via the needleless electrospinning technique using poly(vinyl alcohol) (PVA) with a high molecular weight and with a high degree of hydrolysis with the incorporated PL (10% w/w). The morphology, wettability and protein release from the nanofibers was then assessed from the resulting composite PVA–PL nanomats. The bioactivity of the PVA–PL nanomats was proved in vitro using HaCaT keratinocytes, human saphenous endothelial cells (HSVECs) and 3T3 fibroblasts. The PVA–PL supported cell adhesion, proliferation, and viability. The improved phenotypic maturation of the HaCaT cells due to the PVA–PL was manifested via the formation of intermediate filaments positive for cytokeratin 10. The PVA–PL enhanced both the synthesis of the von Willebrand factor via HSVECs and HSVECs chemotaxis through membranes with 8 µm-sized pores. These results indicated the favorable effects of the PVA–PL nanomats on the three cell types involved in the wound healing process, and established PVA–PL nanomats as a promising candidate for further evaluation with respect to in vivo experiments.


2021 ◽  
Vol 11 (17) ◽  
pp. 7769
Author(s):  
Mohammad Foad Abazari ◽  
Shayan Gholizadeh ◽  
Shohreh Zare Karizi ◽  
Nazanin Hajati Birgani ◽  
Danya Abazari ◽  
...  

Application of wound-healing/dressing biomaterials is amongst the most promising approaches for wound repair through protection from pathogen invasion/contamination, maintaining moisture, absorbing exudates, modulating inflammation, and facilitating the healing process. A wide range of materials are used to fabricate wound-healing/dressing biomaterials. Active wound-healing/dressings are next-generation alternatives for passive biomaterials, which provide a physical barrier and induce different biological activities, such as antibacterial, antioxidant, and proliferative effects. Cellulose-based biomaterials are particularly promising due to their tunable physical, chemical, mechanical, and biological properties, accessibility, low cost, and biocompatibility. A thorough description and analysis of wound-healing/dressing structures fabricated from cellulose-based biomaterials is discussed in this review. We emphasize and highlight the fabrication methods, applied bioactive molecules, and discuss the obtained results from in vitro and in vivo models of cellulose-based wound-healing biomaterials. This review paper revealed that cellulose-based biomaterials have promising potential as the wound-dressing/healing materials and can be integrated with various bioactive agents. Overall, cellulose-based biomaterials are shown to be effective and sophisticated structures for delivery applications, safe and multi-customizable dressings, or grafts for wound-healing applications.


2003 ◽  
Vol 83 (3) ◽  
pp. 835-870 ◽  
Author(s):  
SABINE WERNER ◽  
RICHARD GROSE

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.


2000 ◽  
Vol 14 ◽  
pp. 176-182 ◽  
Author(s):  
T. Yoshizawa ◽  
S. Watanabe ◽  
M. Hirose ◽  
J. Yamamoto ◽  
T. Osada ◽  
...  

2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.


2020 ◽  
Vol 26 (36) ◽  
pp. 4551-4568
Author(s):  
Mohammad Kashif Iqubal ◽  
Sadaf Saleem ◽  
Ashif Iqubal ◽  
Aiswarya Chaudhuri ◽  
Faheem Hyder Pottoo ◽  
...  

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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