Polymeric Nanofibre Scaffold for the Delivery of a Transforming Growth Factor β1 Inhibitor

2017 ◽  
Vol 70 (3) ◽  
pp. 280 ◽  
Author(s):  
Vipul Agarwal ◽  
Fiona M. Wood ◽  
Mark Fear ◽  
K. Swaminathan Iyer
Keyword(s):  
Tissue Engineering ◽  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Normal Skin ◽  
Scar Tissue ◽  
Transforming Growth Factor Β1 ◽  
Collagen I ◽  
Elevated Concentration ◽  
Skin Wound Healing

Skin scarring is a highly prevalent and inevitable outcome of adult mammalian wound healing. Scar tissue is both pathologically and aesthetically inferior to the normal skin owing to elevated concentration of highly orientated collagen I architecture in the innate repaired tissue. With highly invasive surgery being the main treatment modality, there is a great need for alternative strategies to mitigate the problem of scar formation. Tissue engineering approaches using polymeric scaffolds have shown tremendous promise in various disease models including skin wound healing; however, the problem of skin scarring has been greatly overlooked. Herein, we developed an electrospun poly(glycidyl methacrylate) (ES-PGMA) scaffold incorporating a small-molecule antiscarring agent, PXS64. PXS64, a lipophilic neutral analogue of mannose-6-phosphate, has been shown to inhibit the activation of transforming growth factor β1 (TGFβ1). TGFβ1 is a primary protein cytokine regulating the expression of collagen I during wound healing and therefore governs the formation of scar tissue. The nanofibres were tested for biocompatibility as a tissue engineering scaffold and for their efficacy to inhibit TGFβ1 activation in human dermal skin fibroblasts.

scholarly journals Epidermal stem cell-derived exosomes promote skin regeneration by downregulating transforming growth factor-β1 in wound healing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengna Duan ◽  
Yan Zhang ◽  
Haiyang Zhang ◽  
Yupeng Meng ◽  
Ming Qian ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Clinical Setting ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Skin Wound ◽  
Scar Formation ◽  
Dermal Fibroblasts ◽  
Skin Wound Healing ◽  
Tgf Β1

Abstract Background Scar formation, which may be caused by myofibroblast aggregations, is the greatest challenge during skin wound healing in the clinical setting. Studies have indicated that epidermal stem cells (EPSC) improve wound healing and reduce scar formation. Methods We investigated the therapeutic effects of EPSC-derived exosomes (EPSC-Exos) on skin wound healing in a skin-defect rat model. We also examined the roles of EPSC-Exos-specific microRNAs in inhibiting the differentiation of human dermal fibroblasts (HDF) into myofibroblasts. Results We found that EPSC-Exos increased the wound healing rate and reduced scar formation in rats. Also, EPSC-Exos improved the regeneration levels of skin appendages, nerves and vessels, as well as the natural distribution of collagen. Furthermore, we found these functions may be achieved by inhibiting the activity of transforming growth factor-β1 (TGF-β1) and its downstream genes. The results showed that some specific microRNAs, including miR-16, let-7a, miR-425-5p and miR-142-3p, were enriched in EPSC-Exos. EPSC-Exos-specific microRNAs, especially miR-425-5p and miR-142-3p, played vital roles in inhibiting myofibroblast differentiation via reducing the TGF-β1 expression in dermal fibroblasts. Conclusion We found a novel function of EPSC-Exos-specific microRNAs, suggesting that EPSC-Exos might represent a strategy to prevent scar formation during wound healing in the clinical setting.

scholarly journals Microcarriers Based on Glycosaminoglycan-Like Marine Exopolysaccharide for TGF-β1 Long-Term Protection

Marine Drugs ◽  
2019 ◽  
Vol 17 (1) ◽  
pp. 65 ◽  
Author(s):  
Agata Zykwinska ◽  
Mélanie Marquis ◽  
Mathilde Godin ◽  
Laëtitia Marchand ◽  
Corinne Sinquin ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Target Location ◽  
Cartilage Regeneration ◽  
Transforming Growth Factor Β1 ◽  
Hydrogel Matrix ◽  
Vitro Model ◽  
Tgf Β1

Articular cartilage is an avascular, non-innervated connective tissue with limited ability to regenerate. Articular degenerative processes arising from trauma, inflammation or due to aging are thus irreversible and may induce the loss of the joint function. To repair cartilaginous defects, tissue engineering approaches are under intense development. Association of cells and signalling proteins, such as growth factors, with biocompatible hydrogel matrix may lead to the regeneration of the healthy tissue. One current strategy to enhance both growth factor bioactivity and bioavailability is based on the delivery of these signalling proteins in microcarriers. In this context, the aim of the present study was to develop microcarriers by encapsulating Transforming Growth Factor-β1 (TGF-β1) into microparticles based on marine exopolysaccharide (EPS), namely GY785 EPS, for further applications in cartilage engineering. Using a capillary microfluidic approach, two microcarriers were prepared. The growth factor was either encapsulated directly within the microparticles based on slightly sulphated derivative or complexed firstly with the highly sulphated derivative before being incorporated within the microparticles. TGF-β1 release, studied under in vitro model conditions, revealed that the majority of the growth factor was retained inside the microparticles. Bioactivity of released TGF-β1 was particularly enhanced in the presence of highly sulphated derivative. It comes out from this study that GY785 EPS based microcarriers may constitute TGF-β1 reservoirs spatially retaining the growth factor for a variety of tissue engineering applications and in particular cartilage regeneration, where the growth factor needs to remain in the target location long enough to induce robust regenerative responses.

Artificial extracellular matrix delivers TGFb1 regulating myofibroblast differentiation

RSC Advances ◽  
2016 ◽  
Vol 6 (26) ◽  
pp. 21922-21928 ◽  
Author(s):  
Weilu Cheng ◽  
Ruodan Xu ◽  
Dalong Li ◽  
Christian Bortolini ◽  
Jinmei He ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Controlled Release ◽  
Growth Factor ◽  
Cell Viability ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Myofibroblast Differentiation ◽  
Differentiation Capacity ◽  
Artificial Extracellular Matrix

Spatiotemporally controlled release of transforming growth factor β1 from electrospun biomimetic nanofibers realized optimal cell viability and myofibroblast differentiation capacity, which holds great potential in wound healing application.

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