Biophysical regulation of epigenetic state and cell reprogramming

Downing, Timothy L.; Soto, Jennifer; Morez, Constant; Houssin, Timothée; Fritz, Ashley L.; Yuan, F.T.; Chu, Julia; Patel, Shyam; Schaffer, David V.; Wang, Jintao

doi:10.1038/nmat3777

Cited by 424 publications

(398 citation statements)

References 51 publications

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“…Through their physical cues, they have the ability to influence cell adhesion, spreading, proliferation, and differentiation. 2,3 Electrospun materials are mostly produced as nonwoven meshes. However, methods to manufacture electrospun filaments have also been developed, which can be assembled into twisted, braided, or woven structures.…”

Section: Introductionmentioning

confidence: 99%

Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

Mouthuy¹,

Škoc²,

Gašparović³

et al. 2017

IJN

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Electrospun filaments represent a new generation of medical textiles with promising applications in soft tissue repair. A potential strategy to improve their design is to combine them with bioactive molecules. Curcumin, a natural compound found in turmeric, is particularly attractive for its antioxidant, anti-inflammatory, and antimicrobial properties. However, investigating the range of relevant doses of curcumin in materials designed for tissue regeneration has remained limited. In this paper, a wide range of curcumin concentrations was explored and the potential of the resulting materials for soft tissue repair applications was assessed. Polydioxanone (PDO) filaments were prepared with various amounts of curcumin: 0%, 0.001%, 0.01%, 0.1%, 1%, and 10% (weight to weight ratio). The results from the present study showed that, at low doses (≤0.1%), the addition of curcumin has no influence on the spinning process or on the physicochemical properties of the filaments, whereas higher doses lead to smaller fiber diameters and improved mechanical properties. Moreover, filaments with 0.001% and 0.01% curcumin stimulate the metabolic activity and proliferation of normal human dermal fibroblasts (NHDFs) compared with the no-filament control. However, this stimulation is not significant when compared to the control filaments (0%). Highly dosed filaments induce either the inhibition of proliferation (with 1%) or cell apoptosis (with 10%) as a result of the concentrations of curcumin found in the medium (9 and 32 μM, respectively), which are near or above the known toxicity threshold of curcumin (~10 μM). Moreover, filaments with 10% curcumin increase the catalase activity and glutathione content in NHDFs, indicating an increased production of reactive oxygen species resulting from the large concentration of curcumin. Overall, this study suggested that PDO electrospun filaments loaded with low amounts of curcumin are more promising compared with higher concentrations for stimulating tissue repair. This study also highlighted the need to explore lower concentrations when using polymers as PDO, such as those with polycaprolactone and other degradable polyesters.

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Section: Introductionmentioning

confidence: 99%

Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

Mouthuy¹,

Škoc²,

Gašparović³

et al. 2017

IJN

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“…Decreased HDAC activity and up-regulation of the expression of WDR5, a subunit of H3 methyltranferase, by microgrooved surfaces led to increased histone H3 acetylation and methylation. These findings can have important implications in cell biology and nanomedicine in the optimization of biomaterials for cell-engineering applications (Downing et al, 2013). Solid lipid NPs (SLNs), whose lipid matrix is cholesterylbutyrate (Chol-but) could be regarded as suitable and highly effective pro-drug of butyric acid.…”

Section: Soft Nanomaterialsmentioning

confidence: 99%

Nanomedicine and epigenome. Possible health risks

Smolkova

Dušinská

Gábelová

2017

Food and Chemical Toxicology

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a b s t r a c tNanomedicine is an emerging field that combines knowledge of nanotechnology and material science with pharmaceutical and biomedical sciences, aiming to develop nanodrugs with increased efficacy and safety. Compared to conventional therapeutics, nanodrugs manifest higher stability and circulation time, reduced toxicity and improved targeted delivery. Despite the obvious benefit, the accumulation of imaging agents and nanocarriers in the body following their therapeutic or diagnostic application generates concerns about their safety for human health. Numerous toxicology studies have demonstrated that exposure to nanomaterials (NMs) might pose serious risks to humans. Epigenetic modifications, representing a non-genotoxic mechanism of toxicant-induced health effects, are becoming recognized as playing a potential causative role in the aetiology of many diseases including cancer. This review i) provides an overview of recent advances in medical applications of NMs and ii) summarizes current evidence on their possible epigenetic toxicity. To discern potential health risks of NMs, since current data are mostly based upon in vitro and animal models, a better understanding of functional relationships between NM exposure, epigenetic deregulation and phenotype is required.

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“…Poly (dimethyl siloxane) (PDMS) (Sylgard 184, Dow Corning, Midland, MI) was prepared according to the manufacturer's instruction. PDMS was spin-coated onto the patterned silicon wafers to achieve desired thickness (~250 μm), degassed under vacuum, and cured at 75˚C for 1.5 h [6] [16]. The PDMS with micropatterned surface were removed from the template, cut into appropriate shapes and thoroughly cleaned by sonication, treated with Plasma Prep (11050Q-AX) to enhance the surface hydrophilicity, and coated with 2% gelatin for 1.5 hour to promote cell attachment.…”

Section: Fabrication and Characterization Of Pdms Substratesmentioning

confidence: 99%

“…In addition, biophysical cues, in the form of parallel microgrooves on the surface of cell-adhesive PDMS substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency [6]. Alterations in gene expression of human vascular endothelial cells associated with nanotopographic cues [7].…”

mentioning

confidence: 99%

Biomaterial Surface Can Modify HUVEC Morphology and Inflammatory Response by Regulating MicroRNA Expression

Gu¹,

Tian²,

Chen³

et al. 2017

JBM

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Vascular inflammation is an important process which contributes to the pathogenesis of many cardiovascular diseases, such as atherosclerosis. MicroRNAs (miRNAs) have been revealed as novel regulators of vascular inflammation. Prior researches had shown that alterations in gene expression of human umbilical vein endothelial cells (HUVECs) associated with topographic cues. Here, we showed that poly (dimethyl siloxane) (PDMS) substrate of 10 μm width and 3 μm depth parallel microgrooves on the surface could significantly upregulate the expression of anti-inflammatory microRNAs, miR-146a and miR-181b. In addition, the results also showed that TRAF6 and importin-α3, target of miR-146a and miR-181b, respectively, were both down-regulated (P < 0.05 and P < 0.001, respectively). The expression levels of the inflammation related proteins were all significantly decreased, including VCAM-1 (P < 0.05), ICAM-1 (P < 0.001), E-selectin (P < 0.001), and MCP-1 (P < 0.05). The adhesion of the mononuclear cell line, THP-1, was significantly decreased (P < 0.05). The results revealed that morphology modified HUVEC can modulate miR-146a and miR-181b and their downstream biological functions such as decreasing inflammation, suggesting that surface microtopology may affect vascular inflammation in the setting of cardiovascular disease. These interesting findings will facilitate the optimal design of microstructured materials in tissue engineering.

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Biophysical regulation of epigenetic state and cell reprogramming

Cited by 424 publications

References 51 publications

Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

Nanomedicine and epigenome. Possible health risks

Biomaterial Surface Can Modify HUVEC Morphology and Inflammatory Response by Regulating MicroRNA Expression

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