358 research outputs found

    Control of scar tissue formation in the cornea: strategies in clinical and corneal tissue engineering

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    Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation

    Investigating the relationship between surface properties of polymers and protein adsorption [Abstract]

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    Investigating the relationship between surface properties of polymers and protein adsorption [Abstract

    Local Gromov-Witten Invariants are Log Invariants

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    We prove a simple equivalence between the virtual count of rational curves in the total space of an anti-nef line bundle and the virtual count of rational curves maximally tangent to a smooth section of the dual line bundle. We conjecture a generalization to direct sums of line bundles.Comment: 15 pages, version accepted for publication in Advances in Mathematic

    Chemical and topographical effects on cell differentiation and matrix elasticity in a corneal stromal layer model

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    Control and maintenance of the keratocyte phenotype is vital to developing in vitro tissue engineered strategies for corneal repair. In this study the influence of topographical and chemical cues on the mechanical, phenotypical and genotypical behaviour of adult human derived corneal stromal (AHDCS) cells in three dimensional (3D) multi-layered organised constructs is examined. Topographical cues are provided via multiple aligned electrospun nanofiber meshes, which are arranged orthogonally throughout the constructs and are capable of aligning individual cells and permitting cell migration between the layers. The influence of chemical cues is examined using different supplements in culture media. A non-destructive indentation technique and optical coherence tomography are used to determine the matrix elasiticity (elastic modulus) and dimensional changes, respectively. These measurements were indicative of changes in cell phenotype from contractile fibroblasts to quiescent keratocytes over the duration of the experiment and corroborated by qPCR. Constructs containing nanofibers have a higher initial modulus, reduced contraction and organised cell orientation compared to those without nanofibers. Cell-seeded constructs cultured in serum-containing media increased in modulus throughout the culture period and underwent significantly more contraction than constructs cultured in serum-free and insulin-containing media. This implies that the growth factors present in serum promote a fibroblast-like phenotype; qPCR data further validates these observations. These results indicate that the synergistic effect of nanofibers and serum-free media plus insulin supplementation provide the most suitable topographical and chemical environment for reverting corneal fibroblasts to a keratocyte phenotype in a 3D construct

    The effect of collagen ageing on its structure and cellular behaviour

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    Collagen is the most important component in extracellular matrix (ECM) and plays a pivotal role in individual tissue function in mammals. During ageing, collagen structure changes, which can detrimentally affect its biophysical and biomechanical properties due to an accumulation of advanced glycation end-products (AGEs). AGEs have been linked to non-enzymatic cross-linking of proteins resulting in the alteration of mechanical properties of the tissue. In this study we investigate the influence of different aged collagens on the mechanical and contractile properties of reconstituted hydrogel constructs seeded with corneal stromal fibroblasts. A non-destructive indentation technique and optical coherence tomography (OCT) are used to determine the elastic modulus and dimensional changes respectively. It is revealed that the youngest collagen constructs have a higher elastic modulus and increased contraction compared to the older collagen. These results provide new insights into the relationship between collagen molecular structures and their biomechanical properties

    A microscopic and macroscopic study of aging collagen on its molecular structure, mechanical properties, and cellular response

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    During aging, collagen structure changes, detrimentally affecting tissues' biophysical and biomechanical properties due to an accumulation of advanced glycation end-products (AGEs). In this investigation, we conducted a parallel study of microscopic and macroscopic properties of different-aged collagens from newborn to 2-yr-old rats, to examine the effect of aging on fibrillogenesis, mechanical and contractile properties of reconstituted hydrogels from these collagens seeded with or without fibroblasts. In addition to fibrillogenesis of collagen under the conventional conditions, some fibrillogenesis was conducted alongside a 12-T magnetic field, and gelation rate and AGE content were measured. A nondestructive indentation technique and optical coherence tomography were used to determine the elastic modulus and dimensional changes, respectively. It was revealed that in comparison to younger specimens, older collagens exhibited higher viscosity, faster gelation rates, and a higher AGE-specific fluorescence. Exceptionally, only young collagens formed highly aligned fibrils under magnetic fields. The youngest collagen demonstrated a higher elastic modulus and contraction in comparison to the older collagen. We conclude that aging changes collagen monomer structure, which considerably affects the fibrillogenesis process, the architecture of the resulting collagen fibers and the global network, and the macroscopic properties of the formed constructs

    Dissecting the Influence of Protein Flexibility on the Location and Thermodynamic Profile of Explicit Water Molecules in Protein–Ligand Binding

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    Explicit water molecules in the binding site of proteins play a crucial role for protein–ligand association. Recent advances in computer-aided drug discovery methodology allow for an accurate prediction of the localized position and thermodynamic profile of water molecules (i.e., hydration sites) in the binding site. The underlying calculations are based on MD simulations of explicit water molecules in a restrained protein structure. However, the ligand-binding process is typically associated with protein conformational change that influences the position and thermodynamic properties of the hydration site. In this manuscript, we present the developments of two methods to incorporate the influence of protein conformational change on hydration sites either by following the conformational transition step-by-step (method I) or to match the hydration sites of the two transition end states using local coordinate systems (method II). Using these methods, we highlight the difference in the estimated protein desolvation free energy with and without inclusion of protein flexibility. To the best of our knowledge, this is the first study that explicitly studies the influence of protein conformational change on the position and thermodynamic profiles of water molecules and provides methodology to incorporate protein flexibility into the estimation of the desolvation free energy
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