Design, development and characterization of synthetic Bruch’s membranes

Surrao, Denver C.; Greferath, Ursula; Chau, Yu Qian; Skabo, Stuart; Huynh, Mario; Shelat, Kinnari J.; Limnios, Ioannis J.; Fletcher, Erica L.; Liu, Qin

doi:10.1016/j.actbio.2017.09.032

Cited by 24 publications

(33 citation statements)

References 57 publications

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“…104,128,129 Other studies have focused on the protein composition of the RPE-secreted matrix but not on its physical properties. 125,131 Few studies have specifically examined the effect of scaffold stiffness on RPE culture and more work is required to identify the optimal tethering and stiffness properties which will facilitate cocultures models of the outer retina. 117,[131][132][133] Poly lactic-co-glycolic acid is a popular biomaterial for drug delivery and tissue engineering, and is currently being investigated as a vehicle for the subretinal delivery of iPSC-derived RPE to treat AMD.…”

Section: Biosynthetic Bruch's Membranementioning

confidence: 99%

“…125,131 Few studies have specifically examined the effect of scaffold stiffness on RPE culture and more work is required to identify the optimal tethering and stiffness properties which will facilitate cocultures models of the outer retina. 117,[131][132][133] Poly lactic-co-glycolic acid is a popular biomaterial for drug delivery and tissue engineering, and is currently being investigated as a vehicle for the subretinal delivery of iPSC-derived RPE to treat AMD. 36,124 Its advantages include the availability of fabrication methods, biocompatibility, biodegradability, and tunable mechanical properties.…”

Section: Biosynthetic Bruch's Membranementioning

confidence: 99%

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Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine

Ghareeb

Lako

Steel

2020

Stem Cells Translational Medicine

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Stem cell‐derived retinal organoids offer the opportunity to cure retinal degeneration of wide‐ranging etiology either through the study of in vitro models or the generation of tissue for transplantation. However, despite much work in animals and several human pilot studies, satisfactory therapies have not been developed. Two major challenges for retinal regenerative medicine are (a) physical cell‐cell interactions, which are critical to graft function, are not formed and (b) the host environment does not provide suitable queues for development. Several strategies offer to improve the delivery, integration, maturation, and functionality of cell transplantation. These include minimally invasive delivery, biocompatible material vehicles, retinal cell sheets, and optogenetics. Optimizing several variables in animal models is practically difficult, limited by anatomical and disease pathology which is often different to humans, and faces regulatory and ethical challenges. High‐throughput methods are needed to experimentally optimize these variables. Retinal organoids will be important to the success of these models. In their current state, they do not incorporate a representative retinal pigment epithelium (RPE)‐photoreceptor interface nor vascular elements, which influence the neural retina phenotype directly and are known to be dysfunctional in common retinal diseases such as age‐related macular degeneration. Advanced coculture techniques, which emulate the RPE‐photoreceptor and RPE‐Bruch's‐choriocapillaris interactions, can incorporate disease‐specific, human retinal organoids and overcome these drawbacks. Herein, we review retinal coculture models of the neural retina, RPE, and choriocapillaris. We delineate the scientific need for such systems in the study of retinal organogenesis, disease modeling, and the optimization of regenerative cell therapies for retinal degeneration.

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Section: Biosynthetic Bruch's Membranementioning

confidence: 99%

Section: Biosynthetic Bruch's Membranementioning

confidence: 99%

Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine

Ghareeb

Lako

Steel

2020

Stem Cells Translational Medicine

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“…A range of biodegradable polymers have been investigated and discussed at length; including gelatine/polycaprolactone, poly(lactic-co-glycolic acid) (PLGA) and silk fibroin with fibre diameters of 150-400nm [34]. Poly(L-lactic acid) (PLLA) fibres with a diameter of 70nm have been reported, which when coated with laminin allowed RPE cells to grow with phenotypic morphology exhibiting typical apical microvilli as well as exhibiting phagocytic activity [35]. Pre-clinical trials on rats showed PLLA mesh was well tolerated in the retina and could be a potential candidate for a synthetic BM.…”

Section: Materials To Mimic Native Bm Topographymentioning

confidence: 99%

Biomaterials Targeting AMD: Are We There Yet?

Lawless¹,

Hidalgo-Alvarez²,

Haneef³

2020

Preprint

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Age-related macular degeneration (AMD) is the leading cause of central blindness in developed countries. It affects people mainly over the age of 50 years. It is a disease of the macula, an area of the retina responsible for sharp central vision. It particularly affects the Bruch’s membrane (BM); a layer in the retina that acts as the basement upon which retinal pigment epithelial cells (RPE) attach and survive. The pathology of AMD is not fully understood, but age is considered the main risk factor. There are two forms; nonexudative, leading to the end-stage of the disease, called nonexudative (or dry) AMD (90% of cases) where fatty deposits called drusen form under the RPE on top of the BM lifting off the RPE, and neovascular (or wet) AMD (10% of cases) where abnormal new blood vessels grow and push through the BM, bleeding in and disrupting the RPE. Neovascular AMD is well controlled with regular antiangiogenic drug injections of anti-vascular endothelial growth factor (anti-VEGF) into the eye, whereas there is no current treatment for nonexudative AMD. Many research groups across the world are working on a treatment for nonexudative AMD. This review discusses the research currently being conducted including cell therapies, development of cell transplantation membranes, targeting other disease structures in affected retina (i.e. drusen), and drug delivery to the retina using nanoparticles. Finally, we include our research contributing to the field; developing a bioactive membrane intended to function two-fold: target diseased structures and transplant healthy RPE to the desired area.

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“…Much research focuses on developing a synthetic cell transplantation substrate in order to transplant healthy RPE cells onto BM as a treatment for nonexudative AMD (Lu et al, 2012;Liu et al, 2014;Surrao et al, 2017;da Cruz et al, 2018;Tan et al, 2019). The underlying native diseased BM and related structures remain, however, which leaves the potential for healthy transplanted cells to eventually succumb to disease (White and Olabisi, 2017).…”

Section: Introductionmentioning

confidence: 99%

Optimisation of a Novel Bio-Substrate as a Treatment for Atrophic Age-Related Macular Degeneration

McCormick

Pearce

Kaye

et al. 2020

Front. Bioeng. Biotechnol.

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Atrophic age-related macular degeneration (AMD) is the most common form of AMD accounting for 90% of patients. During atrophic AMD the waste/exchange pathway between the blood supply (choroid) and the retinal pigment epithelium (RPE) is compromised. This results in atrophy and death of the RPE cells and subsequently the photoreceptors leading to central blindness. Although the mechanisms behind AMD are unknown, the growth of fatty deposits known as drusen, have been shown to play a role in the disease. There is currently no treatment or cure for atrophic AMD. Much research focuses on developing a synthetic substrate in order to transplant healthy cells to the native Bruch's membrane (BM), however, the diseased native BM and related structures still leave potential for transplanted cells to succumb to disease. In this proof-of-concept work we electrospun poly(ethylene terephthalate) (PET) to fabricate a nanofibrous cytocompatible synthetic BM. The apical surface of the membrane was cultured with ARPE-19 cells and the underside was decorated with poly(lactic acid-co-glycolic acid) (PLGA) or poly(glycolic acid) (PGA) degradable nanoparticles by electrospraying. The membrane exhibited hydrophilicity, high tensile strength and structurally resembled the native BM. ARPE-19 cells were able to form a monolayer on the surface of the membrane and no cell invasion into the membrane was seen. The presence of both PLGA and PGA nanoparticles increased ARPE-19 cell metabolism but had no effect on cell viability. There was a decrease in pH of ARPE-19 cell culture media 7 days following culturing with the PLGA nanoparticles but this change was eliminated by 2 weeks; PGA nanoparticles had no effect on cell culture media pH. The fluorescent dye FITC was encapsulated into nanoparticles and showed sustained release from PLGA nanoparticles for 2 weeks and PGA nanoparticles for 1 day. Future work will focus on encapsulating biologically active moieties to target drusen. This could allow this novel bioactive substrate to be a potential treatment for atrophic AMD that would function twofold: deliver the required monolayer of healthy RPE cells to the macula on a synthetic BM and remove diseased structures within the retina, restoring the waste/exchange pathway and preventing vision loss.

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Design, development and characterization of synthetic Bruch’s membranes

Cited by 24 publications

References 57 publications

Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine

Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine

Biomaterials Targeting AMD: Are We There Yet?

Optimisation of a Novel Bio-Substrate as a Treatment for Atrophic Age-Related Macular Degeneration

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