Topography design in model membranes: Where biology meets physics

Phospholipid membranes are necessary for the compartmentalization of chemistries within biological cells and for initiation and propagation of cell signaling. The morphological and chemical complexities of cellular membranes represent a challenge for dissecting the biochemical processes occurring at these interfaces. Therefore, investigations of the biological events occurring at the membrane require suitable models to reproduce the intricacy of this surface. Solid-supported lipid bilayers (SLBs) are simplified physical replicas of biological membranes that allow for bottom-up reconstruction of the molecular mechanisms occurring at cellular interfaces. In this brief review, we introduce how the properties of SLBs can be tuned to mimic biological membranes, highlighting the engineering approaches for creating spatially resolved patterns of lipid bilayers and supported membranes with curved geometries. Additionally, we present how SLBs have been employed to reconstitute molecular mechanisms involved in intercellular signaling and more recently, membrane trafficking

Dynamic photo-cross-linking of native silk enables macroscale patterning at a microscale resolution

Light-based structuring methods have shown reconstituted silk to be a versatile and appropriate material for a range of optical and biomaterial-based applications. However, without an understanding of how an unmodified, native, silk responds to photoprocessing, the full potential of this material cannot be realized. Here, we show that the use of native silk enables the production of compound patterns with improved resolution and image quality when quantitatively compared to standard reconstituted silk, which we link directly to the influence of molecular weight. Further insights into the mechanism behind silk structure development are provided through mechanical (rheological) and structural (FTIR) measurements and results show that processing can tune properties over several orders of magnitude, enabling potential replication of several soft tissue types. Finally, broadening our application perspective, this combination of mask-less lithography and native silk resulted in the fabrication of transparent optical elements for data storage and labeling

An “off-the shelf” Synthetic Membrane to Simplify Regeneration of Damaged Corneas

yesOur overall aim is to develop a synthetic off-the-shelf alternative to human amniotic membrane which is currently used for delivering cultured limbal stem cells to the cornea in patients who suffer scarring of the cornea because of the loss of limbal stem cells. We have recently reported that both cultured cells and limbal explants grow well on electrospun Poly(D,L-lactide-co-glycolide) (PLGA) (44 kg/mol) with a 50:50 ratio of lactide and glycolide and sterilized with γ-irradiation. Prior to undertaking a clinical study our immediate aim now is to achieve long term storage of the membranes in convenient to use packaging. Membranes were electrospun from Poly(D,L-lactide-co-glycolide) (44 kg/mol) with a 50:50 ratio of lactide and glycolide and sterilized with γ-irradiation and then stored dry (with desiccant) for several months at -80°C and -20°C , Room temperature (UK and India), 37°C and 50°C. We explored the contribution of vacuum sealing and the use of a medical grade bag (PET/Foil/LDPE) to achieve a longer shelf life. Confirmation of membranes being suitable for clinical use was obtained by culturing tissue explants on membranes post storage. When scaffolds were stored dry the rate of breakdown was both temperature and time dependent. At -20°C and -80°C there was no change in fiber diameter over 18 months of storage, and membranes were stable for 12 months at 4°C while at 50°C (above the transition temperature for PLGA) scaffolds lost integrity after several weeks. The use of vacuum packaging and a medical grade bag both improved the storage shelf-life of the scaffolds. The impact of temperature on storage is summarized beneath. We report that this synthetic membrane can be used as an off-the-shelf or-out-of-the freezer alternative to the amniotic membrane for corneal regeneration

Combination of Microstereolithography and Electrospinning to Produce Membranes Equipped with Niches for Corneal Regeneration

We report a technique for the fabrication of micropockets within electrospun membranes in which to study cell behavior. Specifically, we describe a combination of microstereolithography and electrospinning for the production of PLGA (Poly(lactide-co-glycolide)) corneal biomaterial devices equipped with microfeatures

The Tissue-Engineered Vascular Graft-Past, Present, and Future

Cardiovascular disease is the leading cause of death worldwide, with this trend predicted to continue for the foreseeable future. Common disorders are associated with the stenosis or occlusion of blood vessels. The preferred treatment for the long-term revascularization of occluded vessels is surgery utilizing vascular grafts, such as coronary artery bypass grafting and peripheral artery bypass grafting. Currently, autologous vessels such as the saphenous vein and internal thoracic artery represent the gold standard grafts for small-diameter vessels (<6 mm), outperforming synthetic alternatives. However, these vessels are of limited availability, require invasive harvest, and are often unsuitable for use. To address this, the development of a tissue-engineered vascular graft (TEVG) has been rigorously pursued. This article reviews the current state of the art of TEVGs. The various approaches being explored to generate TEVGs are described, including scaffold-based methods (using synthetic and natural polymers), the use of decellularized natural matrices, and tissue self-assembly processes, with the results of various in vivo studies, including clinical trials, highlighted. A discussion of the key areas for further investigation, including graft cell source, mechanical properties, hemodynamics, integration, and assessment in animal models, is then presented

Aligned polyhydroxyalkanoate blend electrospun fibers as intraluminal guidance scaffolds for peripheral nerve repair

The use of nerve guidance conduits (NGCs) to treat peripheral nerve injuries is a favorable approach to the current “gold standard” of autografting. However, as simple hollow tubes, they lack specific topographical and mechanical guidance cues present in nerve grafts and therefore are not suitable for treating large gap injuries (30–50 mm). The incorporation of intraluminal guidance scaffolds, such as aligned fibers, has been shown to increase neuronal cell neurite outgrowth and Schwann cell migration distances. A novel blend of PHAs, P(3HO)/P(3HB) (50:50), was investigated for its potential as an intraluminal aligned fiber guidance scaffold. Aligned fibers of 5 and 8 μm diameter were manufactured by electrospinning and characterized using SEM. Fibers were investigated for their effect on neuronal cell differentiation, Schwann cell phenotype, and cell viability in vitro. Overall, P(3HO)/P(3HB) (50:50) fibers supported higher neuronal and Schwann cell adhesion compared to PCL fibers. The 5 μm PHA blend fibers also supported significantly higher DRG neurite outgrowth and Schwann cell migration distance using a 3D ex vivo nerve injury model

The Lensed Lyman-Alpha MUSE Arcs Sample (LLAMAS)

Aims. We present the Lensed Lyman-Alpha MUSE Arcs Sample (LLAMAS) selected from MUSE and HST observations of 17 lensing clusters. The sample consists of 603 continuum-faint (−23 < MUV < −14) lensed Lyman-α emitters (producing 959 images) with secure spectroscopic redshifts between 2.9 and 6.7. Combining the power of cluster magnification with 3D spectroscopic observations, we were able to reveal the resolved morphological properties of 268 Lyman-α emitters. Methods. We used a forward-modeling approach to model both Lyman-α and rest-frame UV continuum emission profiles in the source plane and measure spatial extent, ellipticity, and spatial offsets between UV and Lyman-α emission. Results. We find a significant correlation between UV continuum and Lyman-α spatial extent. Our characterization of the Lyman-α halos indicates that the halo size is linked to the physical properties of the host galaxy (SFR, Lyman-α equivalent width, Lyman-α line FWHM). We find that 48% of Lyman-α halos are best fit by an elliptical emission distribution with a median axis ratio of q = 0.48. We observe that 60% of galaxies detected both in UV and Lyman-α emission show a significant spatial offset (ΔLyα − UV). We measure a median offset of ΔLyα − UV = 0.58 ± 0.14 kpc for the entire sample. By comparing the spatial offset values with the size of the UV component, we show that 40% of the offsets could be due to star-forming sub-structures in the UV component, while the larger offsets (60%) are more likely due to greater-distance processes such as scattering effects inside the circumgalactic medium or emission from faint satellites or merging galaxies. Comparisons with a zoom-in radiative hydrodynamics simulation of a typical Lyman-α emitting galaxy show a very good agreement with LLAMAS galaxies and indicate that bright star-formation clumps and satellite galaxies could produce a similar spatial offset distribution