scholarly journals The Effect of the Controlled Release of Platelet Lysate from PVA Nanomats on Keratinocytes, Endothelial Cells and Fibroblasts

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.

2018 ◽  
Vol 19 (12) ◽  
pp. 3862 ◽  
Author(s):  
Junhe Shi ◽  
May Barakat ◽  
Dandan Chen ◽  
Lin Chen

Bicellular tight junctions (TJs) are intercellular junctions comprised of a variety of transmembrane proteins including occludin, claudins, and junctional adhesion molecules (JAMs) as well as intracellular scaffold proteins such as zonula occludens (ZOs). TJs are functional, intercellular structures that form a barrier between adjacent cells, which constantly seals and unseals to control the paracellular passage of molecules. They are primarily present in the epithelial and endothelial cells of all tissues and organs. In addition to their well-recognized roles in maintaining cell polarity and barrier functions, TJs are important regulators of signal transduction, which modulates cell proliferation, migration, and differentiation, as well as some components of the immune response and homeostasis. A vast breadth of research data is available on TJs, but little has been done to decipher their specific roles in wound healing, despite their primary distribution in epithelial and endothelial cells, which are essential contributors to the wound healing process. Some data exists to indicate that a better understanding of the functions and significance of TJs in healing wounds may prove crucial for future improvements in wound healing research and therapy. Specifically, recent studies demonstrate that occludin and claudin-1, which are two TJ component proteins, are present in migrating epithelial cells at the wound edge but are absent in chronic wounds. This indicates that functional TJs may be critical for effective wound healing. A tremendous amount of work is needed to investigate their roles in barrier function, re-epithelialization, angiogenesis, scar formation, and in the interactions between epithelial cells, endothelial cells, and immune cells both in the acute wound healing process and in non-healing wounds. A more thorough understanding of TJs in wound healing may shed new light on potential research targets and reveal novel strategies to enhance tissue regeneration and improve wound repair.


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.


Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 457
Author(s):  
Andreu Blanquer ◽  
Jana Musilkova ◽  
Elena Filova ◽  
Johanka Taborska ◽  
Eduard Brynda ◽  
...  

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 961
Author(s):  
Sibusiso Alven ◽  
Vuyolwethu Khwaza ◽  
Opeoluwa O. Oyedeji ◽  
Blessing A. Aderibigbe

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial properties, poor biodegradability and biocompatibility, and weak mechanical performance. Plant extracts, such as Aloe vera, have attracted significant attention in wound management because of their interesting biological properties. Aloe vera is composed of essential constituents beneficial for the wound healing process, such as amino acids, vitamins C and E, and zinc. Aloe vera influences numerous factors that are involved in wound healing and stimulates accelerated healing. This review reports the therapeutic outcomes of aloe vera extract-loaded polymer-based scaffolds in wound management.


2021 ◽  
Vol 18 ◽  
Author(s):  
Xinchi Feng ◽  
Jinsong Hao

: Chronic wounds remain a significant public problem and the development of wound treatments has been a research focus for the past few decades. Despite advances in the products derived from endogenous substances involved in a wound healing process (e.g. growth factors, stem cells, and extracellular matrix), effective and safe wound therapeutics are still limited. There is an unmet need to develop new therapeutics. Various new pathways and targets have been identified and could become a molecular target in designing novel wound agents. Importantly, many existing drugs that target these newly identified pathways could be repositioned for wound therapy, which will facilitate fast translation of research findings to clinical applications. This review discusses the newly identified pathways/targets and their potential uses in the development of wound therapeutics. Some herbs and amphibian skins have been traditionally used for wound repairs and their active ingredients have been found to act in these new pathways. Hence, screening these natural products for novel wound therapeutics remains a viable approach. The outcomes of wound care using natural wound therapeutics could be improved if we can better understand their cellular and molecular mechanisms and fabricate them in appropriate formulations, such as using novel wound dressings and nano-engineered materials. Therefore, we also provide an update on the advances in the wound therapeutics from natural sources. Overall, this review offers new insights into novel wound therapeutics.


Membranes ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 702
Author(s):  
Seyyed-Mojtaba Mousavi ◽  
Zohre Mousavi Nejad ◽  
Seyyed Alireza Hashemi ◽  
Marjan Salari ◽  
Ahmad Gholami ◽  
...  

Despite the advances that have been achieved in developing wound dressings to date, wound healing still remains a challenge in the healthcare system. None of the wound dressings currently used clinically can mimic all the properties of normal and healthy skin. Electrospinning has gained remarkable attention in wound healing applications because of its excellent ability to form nanostructures similar to natural extracellular matrix (ECM). Electrospun dressing accelerates the wound healing process by transferring drugs or active agents to the wound site sooner. This review provides a concise overview of the recent developments in bioactive electrospun dressings, which are effective in treating acute and chronic wounds and can successfully heal the wound. We also discuss bioactive agents used to incorporate electrospun wound dressings to improve their therapeutic potential in wound healing. In addition, here we present commercial dressings loaded with bioactive agents with a comparison between their features and capabilities. Furthermore, we discuss challenges and promises and offer suggestions for future research on bioactive agent-loaded nanofiber membranes to guide future researchers in designing more effective dressing for wound healing and skin regeneration.


2019 ◽  
Vol 7 (11) ◽  
pp. 4444-4471 ◽  
Author(s):  
Young Ju Son ◽  
John W. Tse ◽  
Yiran Zhou ◽  
Wei Mao ◽  
Evelyn K. F. Yim ◽  
...  

Skin and cornea tissues provide protective functions. Therapeutics to injuries aim to enhance wound healing efficiency and quality. Although the tissues share similar anatomic structures and wound healing process, therapeutic strategies differ.


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.


Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3401
Author(s):  
David Meléndez-Martínez ◽  
Luis Fernando Plenge-Tellechea ◽  
Ana Gatica-Colima ◽  
Martha Sandra Cruz-Pérez ◽  
José Manuel Aguilar-Yáñez ◽  
...  

Chronic wounds are a major health problem that cause millions of dollars in expenses every year. Among all the treatments used, active wound treatments such as enzymatic treatments represent a cheaper and specific option with a fast growth category in the market. In particular, bacterial and plant proteases have been employed due to their homology to human proteases, which drive the normal wound healing process. However, the use of these proteases has demonstrated results with low reproducibility. Therefore, alternative sources of proteases such as snake venom have been proposed. Here, we performed a functional mining of proteases from rattlesnakes (Crotalus ornatus, C. molossus nigrescens, C. scutulatus, and C. atrox) due to their high protease predominance and similarity to native proteases. To characterize Crotalus spp. Proteases, we performed different protease assays to measure and confirm the presence of metalloproteases and serine proteases, such as the universal protease assay and zymography, using several substrates such as gelatin, casein, hemoglobin, L-TAME, fibrinogen, and fibrin. We found that all our venom extracts degraded casein, gelatin, L-TAME, fibrinogen, and fibrin, but not hemoglobin. Crotalus ornatus and C. m. nigrescens extracts were the most proteolytic venoms among the samples. Particularly, C. ornatus predominantly possessed low molecular weight proteases (P-I metalloproteases). Our results demonstrated the presence of metalloproteases capable of degrading gelatin (a collagen derivative) and fibrin clots, whereas serine proteases were capable of degrading fibrinogen-generating fibrin clots, mimicking thrombin activity. Moreover, we demonstrated that Crotalus spp. are a valuable source of proteases that can aid chronic wound-healing treatments.


Polymers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 768 ◽  
Author(s):  
María Puertas-Bartolomé ◽  
Blanca Vázquez-Lasa ◽  
Julio San Román

The effective treatment of chronic wounds constitutes one of the most common worldwide healthcare problem due to the presence of high levels of proteases, free radicals and exudates in the wound, which constantly activate the inflammatory system, avoiding tissue regeneration. In this study, we describe a multifunctional bioactive and resorbable membrane with in-built antioxidant agent catechol for the continuous quenching of free radicals as well as to control inflammatory response, helping to promote the wound-healing process. This natural polyphenol (catechol) is the key molecule responsible for the mechanism of adhesion of mussels providing also the functionalized polymer with bioadhesion in the moist environment of the human body. To reach that goal, synthesized statistical copolymers of N-vinylcaprolactam (V) and 2-hydroxyethyl methacrylate (H) have been conjugated with catechol bearing hydrocaffeic acid (HCA) molecules with high yields. The system has demonstrated good biocompatibility, a sustained antioxidant response, an anti-inflammatory effect, an ultraviolet (UV) screen, and bioadhesion to porcine skin, all of these been key features in the wound-healing process. Therefore, these novel mussel-inspired materials have an enormous potential for application and can act very positively, favoring and promoting the healing effect in chronic wounds.


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