Modelling and simulation analysis of porous polymeric scaffold for the replacement of Bruch's membrane as a therapy for age-related macular degeneration (original) (raw)
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Bioengineering, 2021
Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly worldwide. So far, the etiology and the progression of AMD are not well known. Animal models have been developed to study the mechanisms involved in AMD; however, according to the “Three Rs” principle, alternative methods have been investigated. Here we present a strategy to develop a “Three Rs” compliant retinal three-dimensional (3D) in vitro model, including a Bruch’s membrane model and retina pigment epithelium (RPE) layer. First, tensile testing was performed on porcine retina to set a reference for the in vitro model. The results of tensile testing showed a short linear region followed by a plastic region with peaks. Then, Bruch’s membrane (BrM) was fabricated via electrospinning by using Bombyx mori silk fibroin (BMSF) and polycaprolactone (PCL). The BrM properties and ARPE-19 cell responses to BrM substrates were investigated. The BrM model displayed a thickness of 44 µm, with a high po...
Advances in Materials Science and Engineering
One promising treatment for degenerative retinal diseases such as age-related macular degeneration (AMD) is the delivery of retinal pigment epithelial (RPE) cells using degradable scaffolds. Tough-aligned scaffolds are promising candidates for some applications of tissue engineering, such as peripheral nerve regeneration. However, aligned scaffolds have not been investigated in retinal tissue engineering so far. Here, a comparison was made between aligned and random scaffolds fabricated from polycaprolactone (PCL) and human amniotic membrane powder (HAMP) as a scaffold for RPE cells. The effects of alignment on mechanical properties, porosity, hydrophilicity, degradation of the scaffolds, and the cellular interaction of RPE cells were investigated. The results revealed that the aligned scaffold has a lower average fiber diameter, porosity, hydrophilicity, and Young’s modulus and also a higher maximum strain in failure compared with the random scaffold. However, the proliferation of ...
Scientific Reports, 2022
The common retinal diseases are age-related macular degeneration (AMD) and retinitis pigmentosa (RP). They are usually associated with the dysfunction of retinal pigment epithelial (RPE) cells and degeneration of underlying Bruch's membrane. The RPE cell transplantation is the most promising therapeutic option to restore lost vision. This study aimed to construct an ultrathin porous fibrous film with properties similar to that of native Bruch's membrane as carriers for the RPE cells. Human amniotic membrane powder (HAMP)/Polycaprolactone (PCL) scaffolds containing different concentrations of HAMP were fabricated by electrospinning technique. The results showed that with increasing the concentration of HAMP, the diameter of fibers increased. Moreover, hydrophilicity and degradation rate were improved from 119° to 92° and 14 to 56% after 28 days immersion in phosphate-buffered saline (PBS) solution, respectively. All scaffolds had a porosity above 85%. Proper cell adhesion was obtained one day after culture and no toxicity was observed. However, after seven days, the rate of growth and proliferation of ARPE-19 cells, a culture model of RPE, on the PCL-30HAMP scaffold (HAMP concentration in PCL 7.2% by weight) was higher compared to other scaffolds. These results indicated that PCL-30HAMP fibrous scaffold has a great potential to be used in retinal tissue engineering applications. Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in individuals over 50 1. Due to the increase of the aging population, the incidence and burden of AMD are expected to increase alarmingly in the coming years 2. Retinitis pigmentosa (RP) prevalence is approximately 1 in 5000 individuals 3,4. The diseases are characterized by the degeneration of a specific cell layer at the back of the eye, the retinal pigment epithelium, which is essential in retinal function 5. So far, no efficient treatment has been provided for these diseases. Gene therapy and anti-angiogenic drugs just delay the progression of these diseases. One of the best treatments is to replace the destructed cells with new RPE ones 6,7. Cell transplantation may have the potential for retinal regeneration. However, several problems hinder the successful repair of the retina including disorganized or misplaced grafts, as well as reflux of the cells from the injection site, which might lead to serious complications including RPE cell stacking, cell death, and retinal fibrosis. Recent studies have shown that the use of scaffolds can address these obstacles 8,9. The RPE cells are located between the photoreceptors and the underlying Bruch's membrane (BM) which separates the RPE from the blood vessels of the choroid. It is an extracellular matrix with a thickness of 2-4.7 µm that acts as a molecular sieve to maintain the metabolic exchange between the vasculature and outer retina 5,10. Since in AMD the underlying BM is often compromised, the thin scaffold can further act as a prosthetic BM, ensuring the survival, integrity, and functionality of the attached RPE cell monolayer 5. Various membranes have been used as scaffolds for RPE cells, but long-term cell viability and functionality are still largely unknown 9 .
Investigation of highly porous poly(E-Caprolactone) scaffolds
Biomechanica Hungarica, 2008
Porous polycaprolactone based scaffolds were prepared by compression molding and particulate leaching technique. As pore-forming agent, three fractions (125–250 μm, 250–500 μm and 500–1000 μm) of common table salt-grains were utilized during the processing. The porosity was varied from 50 up to 90 percent, and the compressive characteristics were investigated as a function of porosity. The power-law was found valid in the case of compressive characteristics; however due to the manufacturing not only the strain of densification but also the strain of elasticity was highly dependent on the porosity and the salt-grain size. DOI: 10.17489/biohun/2008/1/30
Computational modeling of intraocular drug delivery supplied by porous implants
Drug Delivery and Translational Research, 2021
New and efficient drug delivery to the posterior part of the eye is a growing health necessity worldwide. Current treatment of eye diseases, such as age-related macular degeneration (AMD), relies on repeated intravitreal injections of drug-containing solutions. Such a drug delivery has major drawbacks including short drug life, significant medical service, and high medical cost. In this study, we explored a new approach to controlled drug delivery by introducing unique porous implants. Our computational modeling contained key physiological and anatomical traits. Incompressible flow in a porous media field, including the sclera, choroid, and retina layers, is governed by Darcy law and the time evolution of the drug concentration was solved via three convection-diffusion equations in the three layers, respectively. The computational model was validated by established results from independent studies and experimental data. Simulations of the IgG1 Fab drug delivery to the posterior eye were performed to evaluate the effectiveness of the porous implants for controlled delivery. Overall, our results indicate that drug therapeutic levels in the posterior eye sustain for eight weeks similarly to those using intravitreal injection. We first evaluated the effects of the porous implants on the drug delivery in the posterior layers. Subsequent simulations were carried out with varying porosity values in a porous episcleral implant. We found that the time evolution of drug concentration is distinctively correlated to drug source location and pore size. A correlation between porosity and fluid properties for selected porous implants was revealed for the first time in this study.
A composite material used as a membrane for ophthalmology applications
Composites Science and Technology, 2010
New biomaterials for intracorneal ophthalmologic implants were designed, manufactured and characterized. A composite material in the form of a membrane was manufactured in a two-stage process. The first stage of the process depended on preparation of multidimensional (MD-type) fibrous polymer composite. A stable terpolymer polytetraflouroethylene-co-polyvinylene fluoride-co-polypropylene (PTFE-PVDF-PP) was used as a composite matrix, and sodium alginate-based biopolymer (NA) in the form of short fibres and/or powder were used as porogenic constituents. The composite materials were subjected to physicochemical treatment in order to remove a water soluble biopolymer. The treatment led to about 50% of open porosity within the polymer matrix. Depending on the membrane type the mean pore size determined with SEM microphotographs was 15 to 25 µm. Permeability and durability of the membranes in simulated eye fluid (culture medium enriched with albumin) was tested. The size and shape of the pores before and after the permeability test were compared (SEM), and they depend on the porogen form. Mechanical parameters of the composite materials such as; tensile strength, Young's modulus, and strain to failure were measured. A membrane derived from fibres and particles showed better mechanical properties than a membrane derived from porogen particles. Microstructure and mechanical properties make the membranes a good candidate for ophthamological implants.
Langmuir-Schaefer film deposition onto honeycomb porous films for retinal tissue engineering
Acta Biomaterialia, 2017
Age-related macular degeneration (AMD) is the leading cause of vision loss in senior citizens in the developed world. The disease is characterised by the degeneration of a specific cell layer at the back of the eye-the retinal pigment epithelium (RPE), which is essential in retinal function. The most promising therapeutic option to restore the lost vision is considered to be RPE cell transplantation. This work focuses on the development of biodegradable biomaterials with similar properties to the native Bruch's membrane as carriers for RPE cells. In particular, the breath figure (BF) method was used to create semi-permeable microporous films, which were thereafter used as the substrate for the consecutive Langmuir-Schaefer (LS) deposition of highly organised layers of collagen type I and collagen type IV. The newly developed biomaterials were further characterised in terms of surface porosity, roughness, hydrophilicity, collagen distribution, diffusion properties and hydrolytic stability. Human embryonic stem cell-derived RPE cells (hESC-RPE) cultured on the biomaterials showed good adhesion, spreading and morphology, as well as the expression of specific protein markers. Cell function was additionally confirmed by the assessment of the phagocytic capacity of hESC-RPE. Throughout the study, microporous films consistently showed better results as cell culture materials for 2 hESC-RPE than dip-coated controls. This work demonstrates the potential of the BF-LS combined technologies to create biomimetic prosthetic Bruch's membranes for hESC-RPE transplantation.
Developing methacrylate-based copolymers as an artificial Bruch's membrane substitute
Journal of Biomedical Materials Research Part A, 2012
Age-related macular degeneration (AMD) is the most common cause of blindness in the developed world. There is currently no treatment for the cellular loss, which is characteristic of AMD. Transplantation of retinal pigment epithelium (RPE) cells represents a potential therapy. Because of AMD-related pathology in the native support, Bruch's membrane, transplanted RPE cells require a scaffold to reside on. We present here the development of an electrospun fibrous scaffold derived from methyl methacrylate and poly(ethylene glycol) (PEG) methacrylate for novel application as an RPE scaffold. Scaffolds were chemically modified to improve cell adhesion by functionalization not previously reported for this type of copolymer system. A human RPE cell line was used to investigate cell-scaffold interactions for up to two weeks in vitro. Scanning electron microscopy was used to characterize the fibrous scaffolds and confirm cell attachment. By day 15, cell area was significantly (p < 0.001) enhanced on scaffolds with chemical modification of the PEG chain terminus. In addition, significantly, less-apoptotic cell death was demonstrable on these modified surfaces. V C 2012 Wiley Periodicals, Inc.
Journal of biomedical materials research. Part A, 2016
Deterioration of retina and death of the retinal cells due to age, diabetes or occlusion can cause retinal degeneration which leads to loss of vision. In this study, it is aimed to design a bilayered matrix to mimic the choroid and the Bruch's membrane of the retinal tissue. As choroid, a microchannelled network resembling a fractal tree design was fabricated by photolithography over photocrosslinkable methacrylated hyaluronic acid hydrogel (HAMA). Gelatin or collagen was immobilized into the microchannels to enhance adherence of Human Umbilical Vein Endothelial Cells (HUVEC). At late culture periods (2 weeks), formation of tubular structures due to proliferation of the attached cells was observed. As Bruch's membrane, an electrospun fibroin nanofiber mat was produced to grow retinal pigment epithelium (RPE) cells on. Cellular interactions between RPE and HUVEC in the microchannels were investigated in a co-culture model in a non-contact mode. It was deduced that by combinin...