scholarly journals Thrombin Preconditioning of Extracellular Vesicles Derived from Mesenchymal Stem Cells Accelerates Cutaneous Wound Healing by Boosting Their Biogenesis and Enriching Cargo Content

2019 ◽  
Vol 8 (4) ◽  
pp. 533 ◽  
Author(s):  
Dong Kyung Sung ◽  
Yun Sil Chang ◽  
Se In Sung ◽  
So Yoon Ahn ◽  
Won Soon Park
Keyword(s):  
Wound Healing ◽  
Extracellular Vesicles ◽  
Therapeutic Efficacy ◽  
Tube Formation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Umbilical Cord ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

The aim of this study was to determine the optimal preconditioning regimen for the wound healing therapeutic efficacy of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). To this end, we compared various preconditioning regimens for both the quantitative and qualitative production of MSC-derived EVs, and their therapeutic efficacy for proangiogenic activity in vitro and cutaneous wound healing in vivo. After preconditioning with thrombin (40 U), H2O2 (50 μM), lipopolysaccharide (1 μg/mL), or hypoxia (10% O2), EV secretion was assessed quantitatively by measuring production per cell and protein quantification, and qualitatively by measuring a proteome profiler and an enzyme-linked immunosorbent assay (ELISA) contained within EVs. The therapeutic efficacy of EVs was assessed in vitro by proliferation, migration and tube formation assays of human umbilical cord blood endothelial cells (HUVECs), and in vivo by quantification of cutaneous wound healing. Thrombin preconditioning optimally boosted EV production and enriched various growth factors including vascular endothelial growth factor and angiogenin contained within EVs compared to other preconditioning regimens. Thrombin preconditioning optimally enhanced proliferation, the migration and tube formation of HUVECs in vitro via pERK1/2 and pAKT signaling pathways, and cutaneous wound healing in vivo compared to other preconditioning regimens. Thrombin preconditioning exhibited optimal therapeutic efficacy compared with other preconditioning regimens in promoting proangiogenic activity in vitro and in enhancing cutaneous wound healing in vivo. These preconditioning regimen-dependent variations in therapeutic efficacy might be mediated by boosting EV production and enriching their cargo content.

scholarly journals Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies

2021 ◽  
Author(s):  
Ghazal Shabestani Monfared ◽  
Peter Ertl ◽  
Mario Rothbauer
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Cell Communication ◽  
Lab On A Chip ◽  
Tissue Level ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

scholarly journals Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 793
Author(s):  
Ghazal Shabestani Monfared ◽  
Peter Ertl ◽  
Mario Rothbauer
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Cell Communication ◽  
Lab On A Chip ◽  
Tissue Level ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Cutaneous wound healing is a complex, multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically, and biologically injured area, resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics are therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring, and eliminate chronic wounds. Following the global trend towards the automation, miniaturization, and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay and cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow for precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

scholarly journals Comprehensive Review of Hybrid Collagen and Silk Fibroin for Cutaneous Wound Healing

Materials ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3097 ◽  
Author(s):  
Ruth Naomi ◽  
Juthamas Ratanavaraporn ◽  
Mh Busra Fauzi
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Silk Fibroin ◽  
Synergistic Effects ◽  
In Vivo Studies ◽  
Cutaneous Wound Healing ◽  
Hybrid Scaffold ◽  
Cutaneous Wound

The use of hybridisation strategy in biomaterials technology provides a powerful synergistic effect as a functional matrix. Silk fibroin (SF) has been widely used for drug delivery, and collagen (Col) resembles the extracellular matrix (ECM). This systematic review was performed to scrutinise the outcome of hybrid Col and SF for cutaneous wound healing. This paper reviewed the progress of related research based on in vitro and in vivo studies and the influence of the physicochemical properties of the hybrid in wound healing. The results indicated the positive outcome of hybridising Col and SF for cutaneous wound healing. The hybridisation of these biomaterials exhibits an excellent moisturising property, perfectly interconnected structure, excellent water absorption and retention capacity, an acceptable range of biodegradability, and synergistic effects in cell viability. The in vitro and in vivo studies clearly showed a promising outcome in the acceleration of cutaneous wound healing using an SF and Col hybrid scaffold. The review of this study can be used to design an appropriate hybrid scaffold for cutaneous wound healing. Therefore, this systematic review recapitulated that the hybridisation of Col and SF promoted rapid cutaneous healing through immediate wound closure and reepithelisation, with no sign of adverse events. This paper concludes on the need for further investigations of the hybrid SF and Col in the future to ensure that the hybrid biomaterials are well-suited for human skin.

scholarly journals A Low Molecular Weight Hyaluronic Acid Derivative Accelerates Excisional Wound Healing by Modulating Pro-Inflammation, Promoting Epithelialization and Neovascularization, and Remodeling Collagen

2019 ◽  
Vol 20 (15) ◽  
pp. 3722 ◽  
Author(s):  
Yin Gao ◽  
Yao Sun ◽  
Hao Yang ◽  
Pengyu Qiu ◽  
Zhongcheng Cong ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Wound Healing ◽  
Hyaluronic Acid ◽  
Molecular Mechanisms ◽  
Healing Process ◽  
Low Molecular Weight ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Recent knowledge of the cellular and molecular mechanisms underlying cutaneous wound healing has advanced the development of medical products. However, patients still suffer from the failure of current treatments, due to the complexity of healing process and thus novel therapeutic approaches are urgently needed. Previously, our laboratories produced a range of low molecular weight hyaluronic acid (LMW-HA) fragments, where a proportion of the glucosamine moieties were chemically N-acyl substituted. Specifically, N-butyrylation results in anti-inflammatory properties in a macrophage system, and we demonstrate the importance of N-acyl substituents in modulating the inflammatory response of LMW-HA. We have set up an inter-institutional collaborative program to examine the biomedical applications of the N-butyrylated LMW-HA (BHA). In this study, the potentials of BHA for dermal healing are assessed in vitro and in vivo. Consequently, BHA significantly promotes dermal healing relative to a commercial wound care product. By contrast, the “parent” partially de-acetylated LMW-HA (DHA) and the re-acetylated DHA (AHA) significantly delays wound closure, demonstrating the specificity of this N-acylation of LMW-HA in wound healing. Mechanistic studies reveal that the BHA-mediated therapeutic effect is achieved by targeting three phases of wound healing (i.e., inflammation, proliferation and maturation), demonstrating the significant potential of BHA for clinical translation in cutaneous wound healing.

scholarly journals Exosomes from Human Umbilical Cord Mesenchymal Stem Cells Facilitate Diabetic Wound Healing through miR-221-3p-mediated Enhancement of Angiogenesis

2021 ◽  
Author(s):  
Qian Wei ◽  
Yaxi Wang ◽  
Kui Ma ◽  
Xiaowei Bian ◽  
Qiankun Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Tube Formation ◽  
Human Umbilical Cord ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Abstract Background: Endothelial dysfunction caused by persistent hyperglycemia in diabetes is responsible for impaired angiogenesis in diabetic wounds. Exosomes are considered potential therapeutic tools to promote diabetic wound healing. The aim of this study was to investigate the effects of exosomes secreted by human umbilical cord mesenchymal stem cells (hucMSC-Exos) on angiogenesis under high glucose (HG) conditions in vivo and in vitro and to explore the underlying mechanisms.Methods: HucMSC-Exos were used to treat diabetic wounds and human umbilical vascular endothelial cells (HUVECs) exposed to HG. Wound healing and angiogenesis were assessed in vivo. The biological characteristics of HUVECs were examined in vitro. Expression of pro-angiogenesis genes in HUVECs was also examined by western blotting. The miRNAs contained within hucMSC-Exos were identified using miRNA microarrays and qRT-PCR. The roles of selected miRNAs in angiogenesis were assessed using specific agomirs and inhibitors.Results: In vivo, local application of hucMSC-Exos enhanced wound healing and angiogenesis. In vitro, hucMSC-Exos reduced senescence of HG-treated HUVECs and promoted proliferation, migration, and tube formation by inhibiting phosphatase and tensin homolog (PTEN) expression and activating the AKT/HIF-1α/VEGF pathways. MiR-221-3p was enriched in hucMSC-Exos. In vitro, MiR-221-3p downregulated PTEN and activated the AKT/HIF-1α/VEGF pathway to promote proliferation, migration, and tube formation in HG-treated HUVECs. In vivo, miR-221-3p agomirs mimicked the effects of hucMSC-Exos on wound healing and angiogenesis, whereas miR-221-3p inhibitors reversed their effects.Conclusions: Our findings suggest that hucMSC-Exos have regenerative and protective effects on HG-induced senescence in endothelial cells via transfer of miR-221-3p, thereby accelerating diabetic wound healing. Thus, hucMSC-Exos may be promising therapeutic candidates for improving diabetic wound angiogenesis.

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