Tissue engineering approaches towards the regeneration of biomimetic scaffolds for age-related macular degeneration

Bagewadi, Shambhavi; Parameswaran, Sowmya; Krishnakumar, Subramanian; Sethuraman, Swaminathan; Subramanian, Anuradha

doi:10.1039/d1tb00976a

Cited by 3 publications

(3 citation statements)

References 109 publications

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“…Due to the limitation of PET membrane fabrication, the actual values of membrane thickness may vary up to 60% of the nominal value (10 µm)[ 25 ]. In contrast, the printed scaffold has a uniform thickness of 7 µm, making it suitable for in vivo study and possible for implant purpose[ 2 ].…”

Section: Resultsmentioning

confidence: 99%

“…Age-related macular degeneration (AMD) is a significant cause of permanent visual loss and is estimated to bring a substantial global burden[ 1 ]. With the progression of AMD, retinal pigment epithelium (RPE), a pigmented and polarized monolayer tissue, gradually loses the ability to process the visual signals[ 2 ]. Scaffold-based RPE tissue engineering has been shown promise to build RPE models for discovering therapeutics agents and tissue transplant for patients with AMD[ 3 - 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Tremendous efforts have been put into developing new RPE culture systems from the perspectives of designing and fabricating culturing devices[ 4 , 8 - 10 ]. One of the most important approaches is film casting, which can quickly produce porous membranes with thickness close to Bruch’s membrane[ 2 , 5 , 10 ]. At present, this technique is widely used to build the commercialized permeable inserts, including Transwell ® and Millicell ® cell culture insert[ 11 - 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Electrohydrodynamic Jet-Printed Ultrathin Polycaprolactone Scaffolds Mimicking Bruch’s Membrane for Retinal Pigment Epithelial Tissue Engineering

Liu¹,

Wang²,

Chen³

et al. 2022

IJB

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Age-related macular degeneration (AMD) is the leading cause of visual loss and affects millions of people worldwide. Dysfunction of the retinal pigment epithelium (RPE) is associated with the pathogenesis of AMD. The purpose of this work is to build and evaluate the performance of ultrathin scaffolds with an electrohydrodynamic jet (EHDJ) printing method for RPE cell culture. We printed two types of ultrathin (around 7 μm) polycaprolactone scaffolds with 20 μm and 50 μm pores, which possess mechanical properties resembling that of native human Bruch’s membrane and are biodegradable. Light microscopy and cell proliferation assay showed that adult human retinal pigment epithelial (ARPE-19) cells adhered and proliferated to form a monolayer on the scaffolds. The progress of culture matured on the scaffolds was demonstrated by immunofluorescence (actin, ZO-1, and Na+/K+-ATPase) and Western blot analysis of the respective proteins. The RPE cells cultured on EHDJ-printed scaffolds with 20 μm pores presented higher permeability, higher transepithelial potential difference, and higher expression level of Na+/K+-ATPase than those cultured on Transwell inserts. These findings suggest that the EHDJ printing can fabricate scaffolds that mimic Bruch’s membrane by promoting maturation of RPE cells to form a polarized and functional monolayered epithelium with potential as an in vitro model for studying retinal diseases and treatment methods.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Electrohydrodynamic Jet-Printed Ultrathin Polycaprolactone Scaffolds Mimicking Bruch’s Membrane for Retinal Pigment Epithelial Tissue Engineering

Liu¹,

Wang²,

Chen³

et al. 2022

IJB

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Cytocompatibility of electrospun poly‐L‐lactic acid membranes for Bruch's membrane regeneration using human embryonic stem cell‐derived retinal pigment epithelial cells

Abbasi,

O'Neill

2024

J Biomedical Materials Res

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Cell replacement therapy is under development for dry age‐related macular degeneration (AMD). A thin membrane resembling the Bruch's membrane is required to form a cell‐on‐membrane construct with retinal pigment epithelial (RPE) cells. These cells have been differentiated from human embryonic stem cells (hESCs) in vitro. A carrier membrane is required for cell implantation, which is biocompatible for cell growth and has dimensions and physical properties resembling the Bruch's membrane. Here a nanofiber electrospun poly‐L‐lactic acid (PLLA) membrane is tested for capacity to support cell growth and maturation. The requirements for laminin coating of the membrane are identified here. A porous electrospun nanofibrous PLLA membrane of ∼50 nm fiber diameter was developed as a prototype support for functional RPE cells grown as a monolayer. The need for laminin coating applied to the membrane following treatment with poly‐L‐ornithine (PLO), was identified in terms of cell growth and survival. Test membranes were compared in terms of hydrophilicity after laminin coating, mechanical properties of surface roughness and Young's modulus, porosity and ability to promote the attachment and proliferation of hESC‐RPE cells in culture for up to 8 weeks. Over this time, RPE cell proliferation, morphology, and marker and gene expression, were monitored. The functional capacity of cell monolayers was identified in terms of transepithelial electrical resistance (TEER), phagocytosis of cells, as well as expression of the cytokines, vascular endothelial growth factor (VEGF) and pigment epithelium‐derived factor (PEDF). PLLA polymer fibers are naturally hydrophobic, so their hydrophilicity was improved by pretreatment with PLO for subsequent coating with the bioactive protein laminin. They were then assessed for amount of laminin adsorbed, contact angle and uniformity of coating using scanning electron microscopy (SEM). Pretreatment with 100% PLO gave the best result over 10% PLO treatment or no treatment prior to laminin adsorption with significantly greater surface stiffness and modulus. By 6 weeks after cell plating, the coated membranes could support a mature RPE monolayer showing a dense apical microvillus structure and pigmented 3D polygonal cell morphology. After 8 weeks, PLO (100%)‐Lam coated membranes exhibited the highest cell number, cell proliferation, and RPE barrier function measured as TEER. RPE cells showed the higher levels of specific surface marker and gene expression. Microphthalmia‐associated transcription factor expression was highly upregulated indicating maturation of cells. Functionality of cells was indicated by expression of VEGF and PEDF genes as well as phagocytic capacity. In conclusion, electrospun PLLA membranes coated with PLO‐Lam have the physical and biological properties to support the distribution and migration of hESC‐RPE cells throughout the whole structure. They represent a good membrane candidate for preparation of hESC‐RPE cells as a monolayer for implantation into the subretinal space of AMD patients.

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Chitosan-based nanoparticles for ocular drug delivery

Pal¹,

Pradhan²,

Kim³

et al. 2023

Advances in Biomedical Polymers and Composites

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Tissue engineering approaches towards the regeneration of biomimetic scaffolds for age-related macular degeneration

Abstract: Age-related macular degeneration (AMD) is the third major cause of blindness in people aged above 60 years. It causes dysfunction of retinal pigment epithelium (RPE) and leads to irreversible loss...

Cited by 3 publications

References 109 publications

Electrohydrodynamic Jet-Printed Ultrathin Polycaprolactone Scaffolds Mimicking Bruch’s Membrane for Retinal Pigment Epithelial Tissue Engineering

Electrohydrodynamic Jet-Printed Ultrathin Polycaprolactone Scaffolds Mimicking Bruch’s Membrane for Retinal Pigment Epithelial Tissue Engineering

Cytocompatibility of electrospun poly‐L‐lactic acid membranes for Bruch's membrane regeneration using human embryonic stem cell‐derived retinal pigment epithelial cells

Chitosan-based nanoparticles for ocular drug delivery

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