Development of an in vitro 3D choroidal neovascularization model using chemically induced hypoxia through an ultra-thin, free-standing nanofiber membrane

Park, Sang Min; Lee, Kyoung‐Pil; Huh, Man-Il; Eom, Seongsu; Park, Byeong-Ung; Kim, Ki Hean; Park, Dong Ho; Kim, Dong Sung; Kim, Hong Kyun

doi:10.1016/j.msec.2019.109964

Cited by 22 publications

(16 citation statements)

References 49 publications

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“…However, scientific evidence is limited in the case of angiogenic natural polymers, and experimental studies on synthetic polymers are fairly more abundant than those with naturally-derived polymers. PCL-based electrospun nanofibers are among the most used nanofibrous mats as angiogenic biomaterials in different regenerative models including choroidal neovascularization [113], artery substitute for long-term implantation [114], and smooth muscle tissue [115]. Moreover, PCL copolymers such as poly(lactide-co-ε-caprolactone) (PLCL) have been shown to induce angiogenesis after implantation in a rat model, in which more and larger vessels were formed and penetrated the construct after intraperitoneal implantation compared with subcutaneous implantation [116].…”

Section: Electrospun Nanofibers Meet Angiogenesismentioning

confidence: 99%

Electrospun Nanofibers for Improved Angiogenesis: Promises for Tissue Engineering Applications

et al. 2020

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Angiogenesis (or the development of new blood vessels) is a key event in tissue engineering and regenerative medicine; thus, a number of biomaterials have been developed and combined with stem cells and/or bioactive molecules to produce three-dimensional (3D) pro-angiogenic constructs. Among the various biomaterials, electrospun nanofibrous scaffolds offer great opportunities for pro-angiogenic approaches in tissue repair and regeneration. Nanofibers made of natural and synthetic polymers are often used to incorporate bioactive components (e.g., bioactive glasses (BGs)) and load biomolecules (e.g., vascular endothelial growth factor (VEGF)) that exert pro-angiogenic activity. Furthermore, seeding of specific types of stem cells (e.g., endothelial progenitor cells) onto nanofibrous scaffolds is considered as a valuable alternative for inducing angiogenesis. The effectiveness of these strategies has been extensively examined both in vitro and in vivo and the outcomes have shown promise in the reconstruction of hard and soft tissues (mainly bone and skin, respectively). However, the translational of electrospun scaffolds with pro-angiogenic molecules or cells is only at its beginning, requiring more research to prove their usefulness in the repair and regeneration of other highly-vascularized vital tissues and organs. This review will cover the latest progress in designing and developing pro-angiogenic electrospun nanofibers and evaluate their usefulness in a tissue engineering and regenerative medicine setting.

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Section: Electrospun Nanofibers Meet Angiogenesismentioning

confidence: 99%

Electrospun Nanofibers for Improved Angiogenesis: Promises for Tissue Engineering Applications

et al. 2020

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“…Hypoxia is considered to serve an important role in CNV formation, a critical characteristic of wet AMD and the main cause of visual impairment in patients with subsequent bleeding or fibrosis (6)(7)(8)(49)(50)(51). CoCl 2 -induced chemical hypoxia, a reliable method of mimicking hypoxia (52)(53)(54)(55), was used to imitate the internal environment during choroidal angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…The underlying molecular mechanisms of choroidal neovascularization (CNV) are multifactorial and complicated. Previous studies have demonstrated that hypoxia and ischemia serve important roles in the formation of CNV (5)(6)(7)(8). Multiple hypoxia-induced growth factors and inflammatory cytokines, including VeGF, hypoxia-inducible factor-1α, TnF-α and IL-1, stimulated the progression of CNV (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 96%

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IGFBP‑rP1‑silencing promotes hypoxia‑induced angiogenic potential of choroidal endothelial cells via the RAF/MEK/ERK signaling pathway

et al. 2020

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insulin-like growth factor binding protein-related protein 1 (iGFBP-rP1) has been reported to have various functions in different cellular contexts. our previous investigation discovered that iGFBP-rP1 inhibited retinal angiogenesis in vitro and in vivo by inhibiting the pro-angiogenic effect of VeGF and downregulating VeGF expression. recently, IGFBP-rP1 was confirmed to be downregulated in the aqueous humor of patients with neovascular age-related macular degeneration compared with controls; however, its specific role remains unknown. The present study applied the technique of gene silencing, reverse transcription-quantitative PCR, western blotting, cell viability assays, cell motility assays and tube formation assays. Chemical hypoxic conditions and choroidal endothelial (rF/6a) cells were used to explore the effect of iGFBP-rP1-silencing on the phenotype activation of rF/6a cells under hypoxic conditions and to elucidate the underlying mechanisms. siRNA achieved IGFBP-rP1-silencing in RF/6A cells without cytotoxicity. IGFBP-rP1-silencing significantly restored the viability of rF/6a cells in hypoxia and enhanced hypoxia-induced migration and capillary-like tube formation of RF/6A cells. Furthermore, IGFBP-rP1-silencing significantly upregulated the expression of B-raF, phosphorylated (p)-MeK, perK and VeGF in rF/6a cells under hypoxic conditions; however, these upregulations were inhibited by exogenous iGFBP-rP1. These data indicated that silencing IGFBP-rP1 expression in RF/6A cells effectively promoted the hypoxia-induced angiogenic potential of choroidal endothelial cells by upregulating raF/MeK/erK signaling pathway activation and VeGF expression.

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“…Electrospinning is a simple and versatile way to fabricate a 3D nanofiber mat that emulates the nanofibrous native ECM structure. By modulating the chemical and topographical properties of an electrospun nanofiber membrane, the biochemical and/or biophysical cues can be implemented in an in vitro cell culture platform 22–24 . Various methods, including gel coating, surface modification, and blending hydrogel/polymer, have been developed for the incorporation of natural hydrogels, such as collagen and gelatin, into nanofiber membranes for the purpose of promoting EC proliferation and endothelial barrier formation through biochemical cues 23–27 .…”

Section: Introductionmentioning

confidence: 99%

A collagen gel-coated, aligned nanofiber membrane for enhanced endothelial barrier function

Kim

Eom

Park

et al. 2019

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Herein, a collagen gel-coated and aligned nanofiber membrane named Col-ANM is developed, which remarkably improves endothelial barrier function by providing biochemical and topographical cues simultaneously. Col-ANM is fabricated by collagen gel coating process on an aligned polycaprolactone (PCL) nanofiber membrane, which is obtained by a simple electrospinning process adopting a parallel electrode collector. Human umbilical vein endothelial cells (HUVECs) cultured on Col-ANM exhibit remarkably enhanced endothelial barrier function with high expression levels of intercellular junction proteins of ZO-1 and VE-cadherin, a high TEER, and a cellular permeability compared with the artificial porous membranes in commercial cell culture well inserts. The enhanced endothelial barrier function is conjectured to be attributed to the synergistic effects of topographical and biochemical cues provided by the aligned PCL nanofibers and collagen gel in the Col-ANM, respectively. Finally, the reactive oxygen species is applied to the HUVEC monolayer formed on the Col-ANM to destroy the tight junctions between HUVECs. The destruction of the tight junctions is demonstrated by the decreased TEER value over time. Results indicate the potential of Col-ANM in modeling endothelial barrier dysfunction-related diseases.

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Development of an in vitro 3D choroidal neovascularization model using chemically induced hypoxia through an ultra-thin, free-standing nanofiber membrane

Cited by 22 publications

References 49 publications

Electrospun Nanofibers for Improved Angiogenesis: Promises for Tissue Engineering Applications

Electrospun Nanofibers for Improved Angiogenesis: Promises for Tissue Engineering Applications

IGFBP‑rP1‑silencing promotes hypoxia‑induced angiogenic potential of choroidal endothelial cells via the RAF/MEK/ERK signaling pathway

A collagen gel-coated, aligned nanofiber membrane for enhanced endothelial barrier function

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