This study investigated how substrate geometry influences in-vitro tissue formation at length scales much larger than a single cell. Two-millimetre thick hydroxyapatite plates containing circular ...pores and semi-circular channels of 0.5 mm radius, mimicking osteons and hemi-osteons respectively, were incubated with MC3T3-E1 cells for 4 weeks. The amount and shape of the tissue formed in the pores, as measured using phase contrast microscopy, depended on the substrate geometry. It was further demonstrated, using a simple geometric model, that the observed curvature-controlled growth can be derived from the assembly of tensile elements on a curved substrate. These tensile elements are cells anchored on distant points of the curved surface, thus creating an actin "chord" by generating tension between the adhesion sites. Such a chord model was used to link the shape of the substrate to cell organisation and tissue patterning. In a pore with a circular cross-section, tissue growth increases the average curvature of the surface, whereas a semi-circular channel tends to be flattened out. Thereby, a single mechanism could describe new tissue growth in both cortical and trabecular bone after resorption due to remodelling. These similarities between in-vitro and in-vivo patterns suggest geometry as an important signal for bone remodelling.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, polarized Raman spectroscopy (PRS) was used to characterize the anisotropic response of the amide I band of collagen as a basis for evaluating three-dimensional collagen fibril ...orientation in tissues. Firstly, the response was investigated theoretically by applying classical Raman theory to collagen-like peptide crystal structures. The theoretical methodology was then tested experimentally, by measuring amide I intensity anisotropy in rat tail as a function of the orientation of the incident laser polarization. For the theoretical study, several collagen-like triple-helical peptide crystal structures obtained from the Protein Data Bank were rotated "in plane" and "out of plane" to evaluate the role of molecular orientation on the intensity of the amide I band. Collagen-like peptides exhibit a sinusoidal anisotropic response when rotated "in plane" with respect to the polarized incident laser. Maximal intensity was obtained when the polarization of the incident light is perpendicular to the molecule and minimal when parallel. In the case of "out of plane" rotation of the molecular structure a decreased anisotropic response was observed, becoming completely isotropic when the structure was perpendicular to the plane of observation. The theoretical Raman response of collagen was compared to that of alpha helical protein fragments. In contrast to collagen, alpha helices have a maximal signal when incident light is parallel to the molecule and minimal when perpendicular. For out-of-plane molecular orientations alpha-helix structures display a decreased average intensity. Results obtained from experiments on rat tail tendon are in excellent agreement with the theoretical predictions, thus demonstrating the high potential of PRS for experimental evaluation of the three-dimensional orientation of collagen fibers in biological tissues.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigated the folding of rectangular stimuli-responsive hydrogel-based polymer bilayers with different aspect ratios and relative thicknesses placed on a substrate. It was found that long-side ...rolling dominates at high aspect ratios (ratio of length to width) when the width is comparable to the circumference of the formed tubes, which corresponds to a small actuation strain. Rolling from all sides occurs for higher actuation, namely when the width and length considerably exceed the deformed circumference. In the case of moderate actuation, when both the width and length are comparable to the deformed circumference, diagonal rolling is observed. Short-side rolling was observed very rarely and in combination with diagonal rolling. On the basis of experimental observations, finite-element modeling and energetic considerations, we argued that bilayers placed on a substrate start to roll from corners due to quicker diffusion of water. Rolling from the long-side starts later but dominates at high aspect ratios, in agreement with energetic considerations. We have shown experimentally and by modeling that the main reasons causing a variety of rolling scenarios are (i) non-homogenous swelling due to the presence of the substrate and (ii) adhesion of the polymer to the substrate.
Plant hydro-actuated systems provide a rich source of inspiration for designing autonomously morphing devices. One such example, the pentagonal ice plant seed capsule, achieves complex mechanical ...actuation which is critically dependent on its hierarchical organization. The functional core of this actuation system involves the controlled expansion of a highly swellable cellulosic layer, which is surrounded by a non-swellable honeycomb framework. In this work, we extract the design principles behind the unfolding of the ice plant seed capsules, and use two different approaches to develop autonomously deforming honeycomb devices as a proof of concept. By combining swelling experiments with analytical and finite element modelling, we elucidate the role of each design parameter on the actuation of the prototypes. Through these approaches, we demonstrate potential pathways to design/develop/construct autonomously morphing systems by tailoring and amplifying the initial material's response to external stimuli through simple geometric design of the system at two different length scales.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two important aspects of actuation behavior of stimuli‐responsive hydrogels are the complexity of the shape change and its speed. Here, it is shown that varying the shape of simple polymer bilayers ...can result in very complex and very fast spontaneous folding. The complexity and high folding rate arise from the choice of the shape and from the presence of inhomogeneous swelling within the thermoresponsive layer entrapped between the top hydrophobic layer and the substrate. In contrast to homogeneous swelling of a freestanding bilayer, which leads to a gradual increase of curvature throughout the whole bilayer, inhomogeneous swelling first results in complete rolling of the periphery of the film, which changes its mechanical properties and affects the subsequent morphing process. Further swelling of the thermoresponsive layer generates more stress that builds up until a buckling threshold is overcome, allowing very fast switching from the flat edge‐rolled configuration into a folded one. The research demonstrates how the introduction of holes into actuating bilayers gives rise not only to a novel geometric control over the folding fate of the films but also adds the ability to tune the rate of folding, through the careful selection of hole size, location, and shape.
It is shown that folding of simple polymer bilayers can be very complex and very fast. The complexity and high folding rate arise from the choice of the shape and from the presence of inhomogeneous swelling within the thermoresponsive layer entrapped between the top hydrophobic layer and the substrate.
A highly complex multi‐step folding of isotropic stimuli‐responsive polymer bilayers resulting in a variety of 2D and 3D structures is reported. Experimental observations allow determination of ...empirical rules, which can be used to direct the folding of polymer films in a predictable manner. In particular, it is demonstrated that these rules can be used for the design of a 3D pyramid. The understanding and know‐how attained in this study allow the very simple design of highly complex, self‐folding 3D objects and open new horizons for 3D patterning, important for the design of microfluidic devices, biomaterials, and soft electronics.
Highly complex multi‐step folding of isotropic stimuli‐responsive polymer bilayers results in a variety of 2D and 3D structures. Experimental observations allow determination of empirical rules, which can be used to direct the folding of polymer films in a predictable manner.
The value of adopting the correct modelling methodology has been recognised by national and international bodies who have issued guidance for developing models; for example, the reports generated ...from the recent US Panel on Cost-Effectiveness in Health and Medicine 7 and the collaboration between the International Society for Pharmacoeconomics and Outcomes Research and the Society of Medical-Decision Making (ISPOR-SMDM) 8, 9. ...the UK National Institute of Health and Care Excellence and the US Institute for Clinical and Economic Review are involved in debates around the extent their health economic models should be made publicly available 16, 17. An open source culture allows existing models to be updated to answer new research questions and decision problems and creates a transparent public arena for model validation, education and collaboration across research, industry and healthcare communities 4, 8, 9. The objective of this letter is to highlight the paucity of examples of open source models in the literature and to report on a short piece of research undertaken to gain insight into the appetite of researchers to provide and use open source models. 2 Exploratory Expert Survey An exploratory double-blind survey of health economic stakeholders was undertaken between 25 April, 2016 and 6 May, 2016 to assess whether there is any desire for open source health economic models. To gain access to a wide variety of people with experience and an active interest in health economics, the LinkedIn platform was used to access the relevant groups: ISPOR; HTA in Europe (maintained by EUnetHTA);...
Porous and flexible actuating materials are important for the development of smart systems. We report here a facile method to prepare scalable, flexible actuating porous membranes based on a ...poly(ionic liquid)-modified tissue paper. The targeted membrane property profile was based on synergy of the gradient porous structure of a poly(ionic liquid) network and flexibility of a tissue paper. The gradient porous structure was built through an ammonia-triggered electrostatic complexation of a poly(ionic liquid) with poly(acrylic acid), which were previously impregnated inside the tissue paper. As a result, these porous membranes undergo deformation by bending in response to organic solvents in the vapor or liquid phase and can recover their shape in air, which demonstrates their ability to serve as solvent sensors. Besides, they show enhanced mechanical properties due to the introduction of mechanically flexible tissue paper that allows the membranes to be designed as new responsive textiles and contractile actuators.
Collagen is a versatile structural molecule in nature and is used as a building block in many highly organized tissues, such as bone, skin, and cornea. The functionality and performance of these ...tissues are controlled by their hierarchical organization ranging from the molecular up to macroscopic length scales. In the present study, polarized Raman microspectroscopic and imaging analyses were used to elucidate collagen fibril orientation at various levels of structure in native rat tail tendon under mechanical load. In situ humidity-controlled uniaxial tensile tests have been performed concurrently with Raman confocal microscopy to evaluate strain-induced chemical and structural changes of collagen in tendon. The methodology is based on the sensitivity of specific Raman scattering bands (associated with distinct molecular vibrations, such as the amide I) to the orientation and the polarization direction of the incident laser light. Our results, based on the changing intensity of Raman lines as a function of orientation and polarization, support a model where the crimp and gap regions of collagen hierarchical structure are straightened at the tissue and molecular level, respectively. However, the lack of measurable changes in Raman peak positions throughout the whole range of strains investigated indicates that no significant changes of the collagen backbone occurs with tensing and suggests that deformation is rather redistributed through other levels of the hierarchical structure.
Scaffolds for tissue engineering are usually designed to support cell viability with large adhesion surfaces and high permeability to nutrients and oxygen. Recent experiments support the idea that, ...in addition to surface roughness, elasticity and chemistry, the macroscopic geometry of the substrate also contributes to control the kinetics of tissue deposition. In this study, a previously proposed model for the behavior of osteoblasts on curved surfaces is used to predict the growth of bone matrix tissue in pores of different shapes. These predictions are compared to in vitro experiments with MC3T3‐E1 pre‐osteoblast cells cultivated in two‐millimeter thick hydroxyapatite plates containing prismatic pores with square‐ or cross‐shaped sections. The amount and shape of the tissue formed in the pores measured by phase contrast microscopy confirms the predictions of the model. In cross‐shaped pores, the initial overall tissue deposition is twice as fast as in square‐shaped pores. These results suggest that the optimization of pore shapes may improve the speed of ingrowth of bone tissue into porous scaffolds.
Bone tissue growth depends on the local curvature of the substrate. A simple mathematical model predicts the observations of in vitro tissue growth inside convex and non‐convex pores. Experiments show that tissue growth rates can be doubled by changing the geometry of a prismatic pore from square to cross‐like. Methods based on these observations are proposed to optimize the design of porous scaffolds.
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