Diffusion of nanoparticles in heterogeneous hydrogels as vitreous humour in vitro substitutes.

Nanomedicine has the potential to increase the biostability of drugs to treat retinal diseases, improving their performance and decreasing the required number of intravitreal injections. However, accurate pharmacokinetic studies of these nanoparticle-drug conjugates, nanoparticle motion across the vitreous humour and interaction with the retinal cell layers still need to be investigated. Existing nanoparticle tracking techniques require fluorescent labels, which can impact cytotoxicity, nanoparticles' motion, protein interactions, and cell internalization.

Biomechanical considerations for optimising subretinal injections.

Subretinal injection is the preferred delivery technique for various novel ocular therapies and is widely used because of its precision and efficient delivery of gene and cell therapies; however, choosing an injection point and defining delivery parameters to target a specified retinal location and area is an inexact science. We provide an overview of the key factors that play important roles during subretinal injections to refine the technique, enhance patient outcomes, and minimise risks. We describe the role of anatomical and physical variables that affect subretinal bleb propagation and shape and their impact on retinal integrity.

Replacement of the Trabecular Meshwork Cells-A Way Ahead in IOP Control?

Glaucoma is one of the leading causes of vision loss worldwide, characterised with irreversible optic nerve damage and progressive vision loss. Primary open-angle glaucoma (POAG) is a subset of glaucoma, characterised by normal anterior chamber angle and raised intraocular pressure (IOP). Reducing IOP is the main modifiable factor in the treatment of POAG, and the trabecular meshwork (TM) is the primary site of aqueous humour outflow (AH) and the resistance to outflow.

Towards More Predictive, Physiological and Animal-free Models: Advances in Cell and Tissue Culture 2020 Conference Proceedings.

Experimental systems that faithfully replicate human physiology at cellular, tissue and organ level are crucial to the development of efficacious and safe therapies with high success rates and low cost. The development of such systems is challenging and requires skills, expertise and inputs from a diverse range of experts, such as biologists, physicists, engineers, clinicians and regulatory bodies. Kirkstall Limited, a biotechnology company based in York, UK, organised the annual conference, (ACTC), which brought together people having a variety of expertise and interests, to present and discuss the latest developments in the field of cell and tissue culture and modelling.

Biomechanical properties of retina and choroid: a comprehensive review of techniques and translational relevance.

Studying the biomechanical properties of biological tissue is crucial to improve our understanding of disease pathogenesis. The biomechanical characteristics of the cornea, sclera and the optic nerve head have been well addressed with an extensive literature and an in-depth understanding of their significance whilst, in comparison, knowledge of the retina and choroid is relatively limited. Knowledge of these tissues is important not only to clarify the underlying pathogenesis of a wide variety of retinal and vitreoretinal diseases, including age-related macular degeneration, hereditary retinal dystrophies and vitreoretinal interface diseases but also to optimise the surgical handling of retinal tissues and, potentially, the design and properties of implantable retinal prostheses and subretinal therapies.

Plasma polymer surface modified expanded polytetrafluoroethylene promotes epithelial monolayer formation in vitro and can be transplanted into the dystrophic rat subretinal space.

The aim of this study was to evaluate whether the surface modification of expanded polytetrafluoroethylene (ePTFE) using an n-heptylamine (HA) plasma polymer would allow for functional epithelial monolayer formation suitable for subretinal transplant into a non-dystrophic rat model. Freshly isolated iris pigment epithelial (IPE) cells from two rat strains (Long Evans [LE] and Dark Agouti [DA]) were seeded onto HA, fibronectin-coated n-heptylamine modified (F-HA) and unmodified ePFTE and fibronectin-coated tissue culture (F-TCPS) substrates. Both F-HA ePTFE and F-TCPS substrates enabled functional monolayer formation with both strains of rat.

Silicone oil in vitreoretinal surgery: indications, complications, new developments and alternative long-term tamponade agents.

Silicone oil (SO) has been used as a long-term tamponade agent in the treatment of complicated vitreoretinal diseases for about half a century, during which time many advances in surgical techniques and technologies have been made. This review summarizes the chemical and physical properties of SO, its indications and complications, including particularly emulsification. The mechanisms and risk factors for emulsification are discussed, as well as novel strategies for its effective removal.

Insights into the internal structures of nanogels using a versatile asymmetric-flow field-flow fractionation method.

Poly(-isopropylacrylamide) (pNIPAM) nanogels are a highly researched type of colloidal material. In this work, we establish a versatile asymmetric-flow field-flow fractionation (AF4) method that can provide high resolution particle sizing and also structural information on nanogel samples from 65-310 nm in hydrodynamic diameter and so different chemical compositions. To achieve this online multi-angle light scattering and dynamic light scattering detectors were used to provide measurement of the radius of gyration ( ) and hydrodynamic radius ( ) respectively.

and computational modelling of drug delivery across the outer blood-retinal barrier.

The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate the development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion, due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer blood-retinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow.

Thrombospondin-2 is up-regulated by TGFβ2 and increases fibronectin expression in human trabecular meshwork cells.

Elevated intraocular pressure (IOP) is a major risk factor for the development of primary open-angle glaucoma (POAG). This is from an increased aqueous humour (AH) outflow resistance through the trabecular meshwork (TM). The pathogenic mechanisms leading to the increase in TM outflow resistance are poorly understood but are thought to be from a dysregulation of the TM extracellular matrix (ECM) environment.

Understanding the Phase and Morphological Behavior of Dispersions of Synergistic Dual-Stimuli-Responsive Poly(-isopropylacrylamide) Nanogels.

This work represents a detailed investigation into the phase and morphological behavior of synergistic dual-stimuli-responsive poly(-isopropylacrylamide) nanogels, a material that is of considerable interest as a matrix for in situ forming implants. Nanogels were synthesized with four different diameters (65, 160, 310, and 450 nm) as monodispersed particles. These different samples were then prepared and characterized as both dilute (0.

Modulated release from implantable ocular silicone oil tamponade drug reservoirs.

Complicated cases of retinal detachment can be treated with silicone oil tamponades. There is the potential for silicone oil tamponades to have adjunctive drug releasing behaviour within the eye, however the lipophilic nature of silicone oil limits the number of drugs that are suitable, and drug release from the hydrophobic reservoir is uncontrolled. Here, a radiometric technique was developed to accurately measure drug solubility in silicone oil and measure release into culture media.

The formation of a functional retinal pigment epithelium occurs on porous polytetrafluoroethylene substrates independently of the surface chemistry.

Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells may have the potential to preserve or restore vision in patients affected by blinding diseases such as age-related macular degeneration (AMD). One of the critical steps in achieving this is the ability to grow a functioning retinal pigment epithelium, which may need a substrate on which to grow and to aid transplantation. Tailoring the physical and chemical properties of the substrate should help the engineered tissue to function in the long term.

Controlling drug release from non-aqueous environments: Moderating delivery from ocular silicone oil drug reservoirs to combat proliferative vitreoretinopathy.

In a number of cases of retinal detachment, treatment may require the removal of the vitreous humour within the eye and replacement with silicone oil to aid healing of the retina. The insertion of silicone oil offers the opportunity to also deliver drugs to the inside of the eye; however, drug solubility in silicone oil is poor and release from this hydrophobic drug reservoir is not readily controlled. Here, we have designed a range of statistical graft copolymers that incorporate dimethylsiloxane and ethylene glycol repeat units within the side chains, allowing short chains of oligo(ethylene glycol) to be solubilised within silicone oil and provide hydrogen bond acceptor sites to interact with acid functional drug molecules.

Development of emulsification resistant heavier-than-water tamponades using high molecular weight silicone oil polymers.

Purpose: Developing new blends of heavier-than-water silicone oil tamponade agents containing high molecular weight polydimethylsiloxane polymer for use in vitreoretinal surgery.

Materials And Methods: The viscoelastic properties of heavier-than-water silicone oil blends (30.5% F6H8 + 69.

Novel heavy tamponade for vitreoretinal surgery.

Purpose: The aim of this study was to produce a heavy tamponade with a specific gravity greater than 1.06 g/mL that was optically transparent, could be manufactured using simple processing, could be injected using standard clinical equipment, and would have appropriate biocompatibility.

Methods: Aerosil silica was added to a phenyl trimethicone and mixed via a roller, overhead stirring, and ultrasonics.

Guided gingival fibroblast attachment to titanium surfaces: an in vitro study.

Aim: To assess the potential of gingival fibroblasts to attach in a predetermined linear orientation to a nano-topography of aligned fibres on titanium surfaces and determine the ability of such cells to deposit aligned collagen fibre matrix.

Materials And Methods: smooth glass and rough titanium substrates were coated with polytetrafluoroethylene (PTFE) nano-fibres. Ammonia plasma treatment was used to modify the surface chemistry.

Ocular epithelial transplantation: current uses and future potential.

Visual loss may be caused by a variety of ocular diseases and places a significant burden on society. Replacing or regenerating epithelial structures in the eye has been demonstrated to recover visual loss in a number of such diseases. Several types of cells (e.

Drug delivery systems for the eye.

Topical and systemic administration of drugs to the eye is highly inefficient and there is a need for controlled, sustained release, particularly for conditions that affect the posterior segment. Various nonimplantable and implantable drug delivery devices have been developed. Colloidal carriers may allow targeted drug delivery and afford protection to substances that are sensitive to degradation, particularly RNA/DNA-based treatments.

Skeletal tissue engineering using silk biomaterials.

Silks have been proposed as potential scaffold materials for tissue engineering, mainly because of their physical properties. They are stable at physiological temperatures, flexible and resist tensile and compressive forces. Bombyx mori (silkworm) cocoon silk has been used as a suture material for over a century, and has proved to be biocompatible once the immunogenic sericin coating is removed.