In vitro and in vivo advancement of multifunctional electrospun nanofiber scaffolds in wound healing applications: Innovative nanofiber designs, stem cell approaches, and future perspectives

Author(s):  
Isha Behere ◽  
Ganesh Ingavle
2016 ◽  
Vol 113 (21) ◽  
pp. E2935-E2944 ◽  
Author(s):  
Xiaochen Zhou ◽  
Mingjia Tan ◽  
Mukesh K. Nyati ◽  
Yongchao Zhao ◽  
Gongxian Wang ◽  
...  

MLN4924, also known as pevonedistat, is the first-in-class inhibitor of NEDD8-activating enzyme, which blocks the entire neddylation modification of proteins. Previous preclinical studies and current clinical trials have been exclusively focused on its anticancer property. Unexpectedly, we show here, to our knowledge for the first time, that MLN4924, when applied at nanomolar concentrations, significantly stimulates in vitro tumor sphere formation and in vivo tumorigenesis and differentiation of human cancer cells and mouse embryonic stem cells. These stimulatory effects are attributable to (i) c-MYC accumulation via blocking its degradation and (ii) continued activation of EGFR (epidermal growth factor receptor) and its downstream pathways, including PI3K/AKT/mammalian target of rapamycin and RAS/RAF/MEK/ERK, via inducing EGFR dimerization. Finally, MLN4924 accelerates EGF-mediated skin wound healing in mouse and stimulates cell migration in an in vitro culture setting. Taking these data together, our study reveals that neddylation modification could regulate stem cell proliferation and differentiation and that a low dose of MLN4924 might have a therapeutic value for stem cell therapy and tissue regeneration.


2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
A. Stolzing ◽  
H. Colley ◽  
A. Scutt

Mesenchymal stem cells are showing increasing promise in applications such as tissue engineering and cell therapy. MSC are low in number in bone marrow, and thereforein vitroexpansion is often necessary.In vivo, stem cells often reside within a niche acting to protect the cells. These niches are composed of niche cells, stem cells, and extracellular matrix. When blood vessels are damaged, a fibrin clot forms as part of the wound healing response. The clot constitutes a form of stem cell niche as it appears to maintain the stem cell phenotype while supporting MSC proliferation and differentiation during healing. This is particularly appropriate as fibrin is increasingly being suggested as a scaffold meaning that fibrin-based tissue engineering may to some extent recapitulate wound healing. Here, we describe how fibrin modulates the clonogenic capacity of MSC derived from young/old human donors and normal/diabetic rats. Fibrin was prepared using different concentrations to modulate the stiffness of the substrate. MSC were expanded on these scaffolds and analysed. MSC showed an increased self-renewal on soft surfaces. Old and diabetic cells lost the ability to react to these signals and can no longer adapt to the changed environment.


2009 ◽  
Vol 11 (4) ◽  
pp. 397-404 ◽  

Exploring stem cells is a fascinating task, especially in a discipline where the use of stem cells seems far-fetched at first glance, as is the case in psychiatry. In this article we would like to provide a brief overview of the current situation in relation to the treatment of mental diseases. For reasons that we will explain, this review will focus on affective disorders. The following section will give a more detailed account of stem-cell biology including current basic science approaches presenting in-vivo and in-vitro techniques. The final part will then look into future perspectives of using these stem cells to cure mental illnesses, and discuss the related challenges and opportunities.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaoli Rong ◽  
Wenhui Chu ◽  
Haiying Zhang ◽  
Yusu Wang ◽  
Xiaoyan Qi ◽  
...  

Abstract Background When the deer antler is cast, it leaves a cutaneous wound that can achieve scarless healing due to the presence of antler stem cells (ASCs). This provides an opportunity to study regenerative wound healing. Methods In this study, we investigated the therapeutic effects and mechanism of antler stem cell-conditioned medium (ASC-CM) on cutaneous wound healing in rats. In vitro, we investigated the effects of the ASC-CM on proliferation of HUVEC and NIH-3T3 cell lines. In vivo, we evaluated the effects of ASC-CM on cutaneous wound healing using full-thickness skin punch-cut wounds in rats. Results The results showed that ASC-CM significantly stimulated proliferation of the HUVEC and NIH-3T3 cells in vitro. In vivo, completion of healing of the rat wounds treated with ASC-CM was on day 16 (± 3 days), 9 days (± 2 days) earlier than the control group (DMEM); the area of the wounds treated with ASC-CM was significantly smaller (p < 0.05) than the two control groups. Further molecular characterization showed that the ratios of Col3A1/Col1A2, TGF-β3/TGF-β1, MMP1/TIMP1, and MMP3/TIMP1 significantly increased (p < 0.01) in the healed tissue in the ASC-CM group. Conclusions In conclusion, ASC-CM effectively accelerated the wound closure rate and enhanced the quality of healing, which might be through transforming wound dermal fibroblasts into the fetal counterparts. Therefore, the ASC-CM may have potential to be developed as a novel cell-free therapeutic for scarless wound healing.


2019 ◽  
Vol 28 (1_suppl) ◽  
pp. 160S-165S ◽  
Author(s):  
Yoshiki Kuse ◽  
Hideki Taniguchi

Organ failure manifests severe symptoms affecting the whole body that may cause death. However, the number of organ donors is not enough for patients requiring transplantation worldwide. Illegal transplantation is also sometimes conducted. To help address this concern, primary hepatocytes are clinically transplanted in the liver. However, donor shortage and host rejection via instant blood-mediated inflammatory reactions are worrisome. Induced pluripotent stem cell-derived hepatocyte-like cells have been developed as an alternative treatment. Recently, organoid technology has been developed to investigate the pathology and mechanism of organoids in cultures. Organoids can be transplanted with vascularization and connected to host blood vessels, and functionally mature better in vivo than in vitro. Hepatic organoids improve pathology in liver disease models. In this review, we introduce induced pluripotent stem cell- and organoid-based therapies against liver diseases considering present and future perspectives.


2015 ◽  
Vol 36 (1) ◽  
pp. 1-23 ◽  
Author(s):  
Bizunesh M. Borena ◽  
Ann Martens ◽  
Sarah Y. Broeckx ◽  
Evelyne Meyer ◽  
Koen Chiers ◽  
...  

Mammal skin has a crucial function in several life-preserving processes such as hydration, protection against chemicals and pathogens, initialization of vitamin D synthesis, excretion and heat regulation. Severe damage of the skin may therefore be life-threatening. Skin wound repair is a multiphased, yet well-orchestrated process including the interaction of various cell types, growth factors and cytokines aiming at closure of the skin and preferably resulting in tissue repair. Regardless various therapeutic modalities targeting at enhancing wound healing, the development of novel approaches for this pathology remains a clinical challenge. The time-consuming conservative wound management is mainly restricted to wound repair rather than restitution of the tissue integrity (the so-called “restitutio ad integrum”). Therefore, there is a continued search towards more efficacious wound therapies to reduce health care burden, provide patients with long-term relief and ultimately scarless wound healing. Recent in vivo and in vitro studies on the use of skin wound regenerative therapies provide encouraging results, but more protracted studies will have to determine whether the effect of observed effects are clinically significant and whether regeneration rather than repair can be achieved. For all the aforementioned reasons, this article reviews the emerging field of regenerative skin wound healing in mammals with particular emphasis on growth factor- and stem cell-based therapies.


2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Iruthayapandi Selestin Raja ◽  
Desingh Raj Preeth ◽  
Mohan Vedhanayagam ◽  
Suong-Hyu Hyon ◽  
Dohyung Lim ◽  
...  

AbstractBone is a complex structure with unique cellular and molecular process in its formation. Bone tissue regeneration is a well-organized and routine process at the cellular and molecular level in humans through the activation of biochemical pathways and protein expression. Though many forms of biomaterials have been applied for bone tissue regeneration, electrospun nanofibrous scaffolds have attracted more attention among researchers with their physicochemical properties such as tensile strength, porosity, and biocompatibility. When drugs, antibiotics, or functional nanoparticles are taken as additives to the nanofiber, its efficacy towards the application gets increased. Polyphenol is a versatile green/phytochemical small molecule playing a vital role in several biomedical applications, including bone tissue regeneration. When polyphenols are incorporated as additives to the nanofibrous scaffold, their combined properties enhance cell attachment, proliferation, and differentiation in bone tissue defect. The present review describes bone biology encompassing the composition and function of bone tissue cells and exemplifies the series of biological processes associated with bone tissue regeneration. We have highlighted the molecular mechanism of bioactive polyphenols involved in bone tissue regeneration and specified the advantage of electrospun nanofiber as a wound healing scaffold. As the polyphenols contribute to wound healing with their antioxidant and antimicrobial properties, we have compiled a list of polyphenols studied, thus far, for bone tissue regeneration along with their in vitro and in vivo experimental biological results and salient observations. Finally, we have elaborated on the importance of polyphenol-loaded electrospun nanofiber in bone tissue regeneration and discussed the possible challenges and future directions in this field.


RSC Advances ◽  
2014 ◽  
Vol 4 (60) ◽  
pp. 31618-31642 ◽  
Author(s):  
N. Goonoo ◽  
A. Bhaw-Luximon ◽  
D. Jhurry

An electrospun polymeric-based nanofibrous scaffold mimicking the extracellular matrix and serving as a temporary support for cell growth, adhesion, migration and proliferation.


2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.


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