Abstract:Recent studies in mechanobiology have revealed the importance of cellular and extracellular mechanical properties in regulating cellular function in normal and disease states. Although it is established that cells should be investigated in a three-dimensional (3-D) environment, most techniques available to study mechanical properties on the microscopic scale are unable to do so. In this study, for the first time, we present volumetric images of cellular and extracellular elasticity in 3-D biomaterials using qu… Show more
“…The areas of these bell-shape curves were normalized to unity (or www.nature.com/scientificreports/ 100%) and did not depend on the total sizes of regions used in averaging 15 . Note that similar histograms with bell-shape maxima corresponding to mechanically differently organized zones were presented in recent study 44 for essentially different-type samples (cultures of stem cells seeded in a hydrogel matrix). The so-found four stiffness-distribution functions (with areas normalized to unity) are fairly well separated with small overlaps of no more than 10% of the area between adjacent well-marked peaks (for which the mean stiffness values and standard deviations are presented below).…”
Section: Resultssupporting
confidence: 77%
“…The areas of these bell-shape curves were normalized to unity (or 100%) and did not depend on the total sizes of regions used in averaging 15 . Note that similar histograms with bell-shape maxima corresponding to mechanically differently organized zones were presented in recent study 44 for essentially different-type samples (cultures of stem cells seeded in a hydrogel matrix). Figure 2 Determination of the specific stiffness ranges for morphological constituents of the tumor.…”
Section: Resultssupporting
confidence: 77%
“…2 e). Independent examples can be found in the recent study 44 , where OCE-detection of local stiffness-contrast features down to individual cells embedded in homogeneous hydrogel has been demonstrated).…”
We present a non-invasive (albeit contact) method based on optical coherence elastography (oce) enabling the in vivo segmentation of morphological tissue constituents, in particular, monitoring of morphological alterations during both tumor development and its response to therapies. the method uses compressional OCE to reconstruct tissue stiffness map as the first step. Then the OCE-image is divided into regions, for which the Young's modulus (stiffness) falls in specific ranges corresponding to the morphological constituents to be discriminated. These stiffness ranges (characteristic "stiffness spectra") are initially determined by careful comparison of the "gold-standard" histological data and the OCE-based stiffness map for the corresponding tissue regions. After such pre-calibration, the results of morphological segmentation of oce-images demonstrate a striking similarity with the histological results in terms of percentage of the segmented zones. to validate the sensitivity of the oce-method and demonstrate its high correlation with conventional histological segmentation we present results obtained in vivo on a murine model of breast cancer in comparative experimental study of the efficacy of two antitumor chemotherapeutic drugs with different mechanisms of action. The new technique allowed in vivo monitoring and quantitative segmentation of (1) viable, (2) dystrophic, (3) necrotic tumor cells and (4) edema zones very similar to morphological segmentation of histological images. numerous applications in other experimental/clinical areas requiring rapid, nearly real-time, quantitative assessment of tissue structure can be foreseen.
“…The areas of these bell-shape curves were normalized to unity (or www.nature.com/scientificreports/ 100%) and did not depend on the total sizes of regions used in averaging 15 . Note that similar histograms with bell-shape maxima corresponding to mechanically differently organized zones were presented in recent study 44 for essentially different-type samples (cultures of stem cells seeded in a hydrogel matrix). The so-found four stiffness-distribution functions (with areas normalized to unity) are fairly well separated with small overlaps of no more than 10% of the area between adjacent well-marked peaks (for which the mean stiffness values and standard deviations are presented below).…”
Section: Resultssupporting
confidence: 77%
“…The areas of these bell-shape curves were normalized to unity (or 100%) and did not depend on the total sizes of regions used in averaging 15 . Note that similar histograms with bell-shape maxima corresponding to mechanically differently organized zones were presented in recent study 44 for essentially different-type samples (cultures of stem cells seeded in a hydrogel matrix). Figure 2 Determination of the specific stiffness ranges for morphological constituents of the tumor.…”
Section: Resultssupporting
confidence: 77%
“…2 e). Independent examples can be found in the recent study 44 , where OCE-detection of local stiffness-contrast features down to individual cells embedded in homogeneous hydrogel has been demonstrated).…”
We present a non-invasive (albeit contact) method based on optical coherence elastography (oce) enabling the in vivo segmentation of morphological tissue constituents, in particular, monitoring of morphological alterations during both tumor development and its response to therapies. the method uses compressional OCE to reconstruct tissue stiffness map as the first step. Then the OCE-image is divided into regions, for which the Young's modulus (stiffness) falls in specific ranges corresponding to the morphological constituents to be discriminated. These stiffness ranges (characteristic "stiffness spectra") are initially determined by careful comparison of the "gold-standard" histological data and the OCE-based stiffness map for the corresponding tissue regions. After such pre-calibration, the results of morphological segmentation of oce-images demonstrate a striking similarity with the histological results in terms of percentage of the segmented zones. to validate the sensitivity of the oce-method and demonstrate its high correlation with conventional histological segmentation we present results obtained in vivo on a murine model of breast cancer in comparative experimental study of the efficacy of two antitumor chemotherapeutic drugs with different mechanisms of action. The new technique allowed in vivo monitoring and quantitative segmentation of (1) viable, (2) dystrophic, (3) necrotic tumor cells and (4) edema zones very similar to morphological segmentation of histological images. numerous applications in other experimental/clinical areas requiring rapid, nearly real-time, quantitative assessment of tissue structure can be foreseen.
“…Quantitative micro-elastography (QME) of hASCs encapsulated in 3D GelMA hydrogels demonstrated elevated cell and extracellular elasticity in 3D. Interestingly, there was an observed increase in elasticity (>10 kPa) in GelMA containing TAZ-activated hASCs ( Hepburn et al, 2020 ).…”
Section: Mechanobiological Responses Of Stem Cells To Biophysical Andmentioning
Mechanobiology has underpinned many scientific advances in understanding how biophysical and biomechanical cues regulate cell behavior by identifying mechanosensitive proteins and specific signaling pathways within the cell that govern the production of proteins necessary for cell-based tissue regeneration. It is now evident that biophysical and biomechanical stimuli are as crucial for regulating stem cell behavior as biochemical stimuli. Despite this, the influence of the biophysical and biomechanical environment presented by biomaterials is less widely accounted for in stem cell-based tissue regeneration studies. This Review focuses on key studies in the field of stem cell mechanobiology, which have uncovered how matrix properties of biomaterial substrates and 3D scaffolds regulate stem cell migration, self-renewal, proliferation and differentiation, and activation of specific biological responses. First, we provide a primer of stem cell biology and mechanobiology in isolation. This is followed by a critical review of key experimental and computational studies, which have unveiled critical information regarding the importance of the biophysical and biomechanical cues for stem cell biology. This review aims to provide an informed understanding of the intrinsic role that physical and mechanical stimulation play in regulating stem cell behavior so that researchers may design strategies that recapitulate the critical cues and develop effective regenerative medicine approaches.
“…Whilst these existing high resolution variants of optical elastography offer capabilities to image at, or close to, the cellular scale, to imaging depths of hundreds of micrometres to several millimetres, they typically rely on expensive imaging systems that restrict application of optical elastography to niche areas, such as tumour margin assessment 22 . Furthermore, existing techniques may not be practical in low-resource and remote settings 33 – 35 . Another challenge is that techniques such as OCE and Brillouin microscopy are not easily used by non-optics experts as they contain complex optical components that require careful alignment, thus precluding a broader application of the technology.…”
Optical elastography is undergoing extensive development as an imaging tool to map mechanical contrast in tissue. Here, we present a new platform for optical elastography by generating sub-millimetre-scale mechanical contrast from a simple digital camera. This cost-effective, compact and easy-to-implement approach opens the possibility to greatly expand applications of optical elastography both within and beyond the field of medical imaging. Camera-based optical palpation (CBOP) utilises a digital camera to acquire photographs that quantify the light intensity transmitted through a silicone layer comprising a dense distribution of micro-pores (diameter, 30–100 µm). As the transmission of light through the micro-pores increases with compression, we deduce strain in the layer directly from intensity in the digital photograph. By pre-characterising the relationship between stress and strain of the layer, the measured strain map can be converted to an optical palpogram, a map of stress that visualises mechanical contrast in the sample. We demonstrate a spatial resolution as high as 290 µm in CBOP, comparable to that achieved using an optical coherence tomography-based implementation of optical palpation. In this paper, we describe the fabrication of the micro-porous layer and present experimental results from structured phantoms containing stiff inclusions as small as 0.5 × 0.5 × 1 mm. In each case, we demonstrate high contrast between the inclusion and the base material and validate both the contrast and spatial resolution achieved using finite element modelling. By performing CBOP on freshly excised human breast tissue, we demonstrate the capability to delineate tumour from surrounding benign tissue.
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