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.
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.
Ultrasensitive polymer actuators are prepared, which can sense a very small amount (0.25 mol%) of acetone solvent in water, discriminate butanol isomers, and perform cooperative actuation.
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.
Fast actuation speed, large-shape deformation and robust responsiveness are critical to synthetic soft actuators. A simultaneous optimization of all these aspects without trade-offs remains ...unresolved. Here we describe porous polymer actuators that bend in response to acetone vapour (24 kPa, 20 °C) at a speed of an order of magnitude faster than the state-of-the-art, coupled with a large-scale locomotion. They are meanwhile multi-responsive towards a variety of organic vapours in both the dry and wet states, thus distinctive from the traditional gel actuation systems that become inactive when dried. The actuator is easy-to-make and survives even after hydrothermal processing (200 °C, 24 h) and pressing-pressure (100 MPa) treatments. In addition, the beneficial responsiveness is transferable, being able to turn 'inert' objects into actuators through surface coating. This advanced actuator arises from the unique combination of porous morphology, gradient structure and the interaction between solvent molecules and actuator materials.
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.
The first hygroscopically tunable cloth actuator is realized via impregnation of a commercial cloth template by a three dimensionally (3D) nanoporous polymer/carbon nanotube hybrid network. The ...nanoporous hybrid guarantees diffusion of water into the cloth actuator and amplifies the deformation scale. The cloth actuators are mechanically stable with high tensile strength. Because the commercial cotton cloth is inexpensive, such actuators capable of complex motions can be produced in a large size and scale for a wide variety of utilities (e.g. electric generators and “smart” materials).
The first hygroscopic tunable cloth actuator is realized via modification of a commercial cloth template by a 3D nanoporous polymer hybrid. The nanoporous hybrid guarantees fast water diffusion and amplifies deformation. The cloth actuator achieves a large‐scale size production, tunable motion, high tensile strength, and mechanical flexibility with a breadth of utilities (e.g., electric generator and “smart” materials).
Tissue formation is determined by uncountable biochemical signals between cells; in addition, physical parameters have been shown to exhibit significant effects on the level of the single cell. ...Beyond the cell, however, there is still no quantitative understanding of how geometry affects tissue growth, which is of much significance for bone healing and tissue engineering. In this paper, it is shown that the local growth rate of tissue formed by osteoblasts is strongly influenced by the geometrical features of channels in an artificial three-dimensional matrix. Curvature-driven effects and mechanical forces within the tissue may explain the growth patterns as demonstrated by numerical simulation and confocal laser scanning microscopy. This implies that cells within the tissue surface are able to sense and react to radii of curvature much larger than the size of the cells themselves. This has important implications towards the understanding of bone remodelling and defect healing as well as towards scaffold design in bone tissue engineering.
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A myriad of shapes are found in biological tissues, often naturally evolved to fulfill a particular function. In the field of tissue engineering, substrate geometry influences cell ...behavior and tissue formation in vitro, yet little is known how this translates to an in vivo scenario. Here we investigate scaffold curvature-induced tissue growth, without additional growth factors or cells, in an ovine animal model. We show that soft tissue formation follows a curvature-driven tissue growth model. The highly organized endogenous soft matrix, potentially under mechanical strain, leads to a non-standard form of biomineralization, whereby the pre-existing organic matrix is mineralized without collagen remodeling and without an intermediate cartilage ossification phase. Micro- and nanoscale characterization of the tissue microstructure using histology, backscattered electron (BSE) and second-harmonic generation (SHG) imaging and synchrotron small angle X-ray scattering (SAXS) revealed (i) continuous collagen fibers across the soft-hard tissue interface on the tip of mineralized cones, and (ii) bone remodeling by basic multicellular units (BMUs) in regions adjacent to the native cortical bone. Thus, features of soft tissue-to-bone interface resembling the insertion sites of ligaments and tendons into bone were created, using a scaffold that did not mimic the structural or biological gradients across such a complex interface at its mature state. This study provides fundamental knowledge for biomimetic scaffold design in the fields of bone regeneration and soft tissue-to-bone interface tissue engineering.
Geometry influences cell behavior and tissue formation in vitro. However, little is known how this translates to an in vivo scenario. Here we investigate the influence of scaffold mean surface curvature on in vivo tissue growth using an ovine animal model. Based on a multiscale tissue microstructure characterization, we show a seamless integration of soft tissue into newly formed bone, resembling the insertion sites of ligaments and tendons into bone. This interface was created using a scaffold without additional growth factors or cells that did not recapitulate the structural or biological gradients across such a complex tissue interface at its mature state. These findings have important implications for biomimetic scaffold design for bone regeneration and soft tissue-to-bone interface tissue engineering.
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.
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