Debiased ambient vibrations optical coherence elastography to profile cell, organoid and tissue mechanical properties.

The role of the mechanical environment in defining tissue function, development and growth has been shown to be fundamental. Assessment of the changes in stiffness of tissue matrices at multiple scales has relied mostly on invasive and often specialist equipment such as AFM or mechanical testing devices poorly suited to the cell culture workflow.In this paper, we have developed a unbiased passive optical coherence elastography method, exploiting ambient vibrations in the sample that enables real-time noninvasive quantitative profiling of cells and tissues. We demonstrate a robust method that decouples optical scattering and mechanical properties by actively compensating for scattering associated noise bias and reducing variance. The efficiency for the method to retrieve ground truth is validated in silico and in vitro, and exemplified for key applications such as time course mechanical profiling of bone and cartilage spheroids, tissue engineering cancer models, tissue repair models and single cell. Our method is readily implementable with any commercial optical coherence tomography system without any hardware modifications, and thus offers a breakthrough in on-line tissue mechanical assessment of spatial mechanical properties for organoids, soft tissues and tissue engineering.

Static bistability of spherical caps.

Depending on its geometry, a spherical shell may exist in one of two stable states without the application of any external force: there are two 'self-equilibrated' states, one natural and the other inside out (or 'everted'). Though this is familiar from everyday life-an umbrella is remarkably stable, yet a contact lens can be easily turned inside out-the precise shell geometries for which bistability is possible are not known. Here, we use experiments and finite-element simulations to determine the threshold between bistability and monostability for shells of different solid angle. We compare these results with the prediction from shallow shell theory, showing that, when appropriately modified, this offers a very good account of bistability even for relatively deep shells. We then investigate the robustness of this bistability against pointwise indentation. We find that indentation provides a continuous route for transition between the two states for shells whose geometry makes them close to the threshold. However, for thinner shells, indentation leads to asymmetrical buckling before snap-through, while also making these shells more 'robust' to snap-through. Our work sheds new light on the robustness of the 'mirror buckling' symmetry of spherical shell caps.

Regimes of wrinkling in pressurized elastic shells.

We consider the point indentation of a pressurized elastic shell. It has previously been shown that such a shell is subject to a wrinkling instability as the indentation depth is quasi-statically increased. Here we present detailed analysis of this wrinkling instability using a combination of analytical techniques and finite-element simulations. In particular, we study how the number of wrinkles observed at the onset of instability grows with increasing pressurization. We also study how, for fixed pressurization, the number of wrinkles changes both spatially and with increasing indentation depth beyond onset. This 'Far from threshold' analysis exploits the largeness of the wrinkle wavenumber that is observed at high pressurization and leads to quantitative differences with the standard 'Near threshold' stability analysis.This article is part of the themed issue 'Patterning through instabilities in complex media: theory and applications.'

Repair of osteochondral defects in the minipig model by OPF hydrogel loaded with adipose-derived mesenchymal stem cells.

AIM: Critical knee osteochondral defects in seven adult minipigs were treated with oligo(polyethylene glycol)fumarate (OPF) hydrogel combined with autologous or human adipose-derived stem cells (ASCs), and evaluated after 6 months. METHODS: Four defects were made on the peripheral part of right trochleas (n = 28), and treated with OPF scaffold alone or pre-seeded with ASCs. RESULTS: A better quality cartilage tissue characterized by improved biomechanical properties and higher collagen type II expression was observed in the defects treated by autologous or human ASC-loaded OPF; similarly this approach induced the regeneration of more mature bone with upregulation of collagen type I expression. CONCLUSION: This study provides the evidence that both porcine and human adipose-derived stem cells associated to OPF hydrogel allow improving osteochondral defect regeneration in a minipig model.

A quantitative interpretation of the response of articular cartilage to atomic force microscopy-based dynamic nanoindentation tests.

In this paper, a quantitative interpretation for atomic force microscopy-based dynamic nanoindentation (AFM-DN) tests on the superficial layers of bovine articular cartilage (AC) is provided. The relevant constitutive parameters of the tissue are estimated by fitting experimental results with a finite element model in the frequency domain. Such model comprises a poroelastic stress-strain relationship for a fibril reinforced tissue constitution, assuming a continuous distribution of the collagen network orientations. The identification procedure was first validated using a simplified transversely isotropic constitutive relationship; then, the experimental data were manually fitted by using the continuous distribution fibril model. Tissue permeability is derived from the maximum value of the phase shift between the input harmonic loading and the harmonic tissue response. Tissue parameters related to the stiffness are obtained from the frequency response of the experimental storage modulus and phase shift. With this procedure, an axial to transverse stiffness ratio (anisotropy ratio) of about 0.15 is estimated.