Engineered Extracellular Matrices as Biomaterials of Tunable Composition and Function

Engineered and decellularized extracellular matrices (ECM) are receiving increasing interest in regenerative medicine as materials capable to induce cell growth/differentiation and tissue repair by physiological presentation of embedded cues. However, ECM production/decellularization processes and control over their composition remain primary challenges. This study reports engineering of ECM materials with customized properties, based on genetic manipulation of immortalized and death‐inducible human mesenchymal stromal cells (hMSC), cultured within 3D porous scaffolds under perfusion flow. The strategy allows for robust ECM deposition and subsequent decellularization by deliberate cell‐apoptosis induction. As compared to standard production and freeze/thaw treatment, this grants superior preservation of ECM, leading to enhanced bone formation upon implantation in calvarial defects. Tunability of ECM composition and function is exemplified by modification of the cell line to overexpress vascular endothelial growth factor alpha (VEGF), which results in selective ECM enrichment and superior vasculature recruitment in an ectopic implantation model. hMSC lines culture under perfusion‐flow is pivotal to achieve uniform scaffold decoration with ECM and to streamline the different engineering/decellularization phases in a single environmental chamber. The findings outline the paradigm of combining suitable cell lines and bioreactor systems for generating ECM‐based off‐the‐shelf materials, with custom set of signals designed to activate endogenous regenerative processes.     

On finite-element implementation strategies of Schapery-type constitutive theories

This paper presents two new strategies for implementing Schapery-type nonlinearly viscoelastic constitutive theories into finite element codes. The first strategy uses the original differential equations that lead to the integral formulation of Schapery-type constitutive theories and Finite Difference (FD) schemes. This strategy is quite different from all the other strategies found in the literature. The second strategy is an improvement of recursive strategies, used by many authors, based on the integral formulation of the constitutive theory. The performances of the new algorithms are compared with those of existing strategies for various load histories and nonlinearities. It is shown that the newly developed strategy based on FD schemes can exhibit quadratic convergence rate when one time step is stored and 4th order convergence rate when two time steps are stored, which is a major improvement over the recursive strategies.     

Multi-Material 3D Microprinting of Magnetically Deformable Biocompatible Structures

Two-photon polymerization (2PP) allows precise 3D printing at the micrometer scale, and by associating it with magnetic materials, the creation of remotely actuatable micro-structures. Such structures attract a growing interest for biomedical applications, thanks to their size and to the biocompatibility of some photoresist materials. Gelatin methacryloyl (Gel-MA) is one such material, and can be used to create physiological scaffolds for cell culture. Here, the physico-chemical properties of two resins are exploited, the first being a silica-based hybrid polymer, the OrmoComp, and the second a Gel-MA-based hydrogel. A 2PP manufacturing protocol is defined and designed to print both materials in succession as a single structure, which is then linked to a neodymium-iron-boron (NdFeB) magnetic bead for actuation. By this combination, a magnetically deformable 3D culture substrate is created to study cells in an environment that mimics soft, curved, and dynamic properties of tissues in vivo. The structure is actuated via an external magnetic field and bends back and forth along its longest axis. Lastly, preliminary cell culture trials are conducted showing the proliferation of cells on the structures.     

Enhanced Electrocaloric Response of Vinylidene Fluoride–Based Polymers via One-Step Molecular Engineering

Electrocaloric refrigeration is one of the most promising environmentally-friendly technologies to replace current cooling platforms—if a notable electrocaloric effect (ECE) is realized around room temperature where the highest need is. Here, a straight-forward, one-pot chemical modification of P(VDF-ter-TrFE-ter-CTFE) is reported through the controlled introduction of small fractions of double bonds within the backbone that, very uniquely, decreases the lamellar crystalline thickness while, simultaneously, enlarging the crystalline coherence along the a-b plane. This increases the polarizability and polarization without affecting the degree of crystallinity or amending the crystal unit cell—undesirable effects observed with other approaches. Specifically, the permittivity increases by >35%, from 52 to 71 at 1 kHz, and ECE improves by >60% at moderate electric fields. At 40 °C, an adiabatic temperature change >2 K is realized at 60 MV m⁻¹ (>5.5 K at 192 MV m⁻¹), compared to ≈1.3 K for pristine P(VDF-ter-TrFE-ter-CTFE), highlighting the promise of a simple, versatile approach that allows direct film deposition without requiring any post-treatment such as mechanical stretching or high-temperature annealing for achieving the desired performance.     

Small Molecule‐Based Fluorescent Organic Nanoassemblies with Strong Hydrogen Bonding Networks for Fine Tuning and Monitoring Drug Delivery in Cancer Cells

Bright supramolecular fluorescent organic nanoassemblies (FONs), based on strongly polar red‐emissive benzothiadiazole fluorophores containing acidic units, are fabricated to serve as theranostic tools with large colloidal stability in the absence of a polymer or surfactant. High architectural cohesion is ensured by the multiple hydrogen‐bonding networks, reinforced by the dipolar and hydrophobic interactions developed between the dyes. Such interactions are harnessed to ensure high payload encapsulation and efficient trapping of hydrophobic and hydrogen‐bonding drugs like doxorubicin, as shown by steady state and time‐resolved measurements. Fine tuning of the drug release in cancer cells is achieved by adjusting the structure and combination of the fluorophore acidic units. Notably delayed drug delivery is observed by confocal microscopy compared to the entrance of hydrosoluble doxorubicin, demonstrating the absence of undesirable burst release outside the cells by using FONs. Since FON‐constituting fluorophores exhibit a large emission shift from red to green when dissociating in contact with the lipid cellular content, drug delivery could advantageously be followed by dual‐color spectral detection, independently of the drug staining potentiality.     

Comparison Between Robust and Stochastic Optimisation for Long-term Reservoir Management Under Uncertainty

Long-term reservoir management often uses bounds on the reservoir level, between which the operator can work. However, these bounds are not always kept up-to-date with the latest knowledge about the reservoir drainage area, and thus become obsolete. The main difficulty with bounds computation is to correctly take into account the high uncertainty about the inflows to the reservoir. In this article, we propose a methodology to derive minimum bounds while providing formal guarantees about the quality of the obtained solutions. The uncertainty is embedded using either stochastic or robust programming in a model-predictive-control framework. We compare the two paradigms to the existing solution for a case study and find that the obtained solutions vary substantially. By combining the stochastic and the robust approaches, we also assign a confidence level to the solutions obtained by stochastic programming. The proposed methodology is found to be both efficient and easy to implement. It relies on sound mathematical principles, ensuring that a global optimum is reached in all cases.     

Characterization of meso-scale mechanical properties of Longmaxi shale using grid microindentation experiments

Mechanical properties,such as the hardness H,Young's modulus E,creep modulus C,and fracture toughness Kc,are essential parameters in the design of hydraulic fracturing systems for prospective shale gas formations.In this study,a practical methodology is presented for obtaining these properties through microindentation experiments combined with quantitative observations of the mineralogical phases using X-ray diffraction(XRD),scanning electron microscopy(SEM) with backscattered electron(BSE)imaging,and energy-dispersive X-ray spectroscopy(EDS) analyses.We apply this method in the case of three types of Longmaxi shales with different mineralogies(i.e.carbonate-,clay-,and quartz-rich,respectively),which allows us to determine the characteristic indentation depth,h_c=8-10 μm,beyond which the mechanical response of the carbonate-rich shale is homogeneous and independent of its complex heterogeneous microstructure.Moreover,exploiting the results of a large number of indentation tests,we demonstrate that the indentation modulus M of the shale increases as a power-law of hardness H,and its creep modulus C increases linearly with H.We also compute the fracture toughness Kc from the indentation data by assuming a perfectly plastic behavior of the sample.Our results are in good agreement with independent measurements of Kc determined by microscratch tests.Finally,further tests on quartz-and clay-rich samples of the Longmaxi shale suggest further variations in the samples' mechanical properties depending on their burial conditions and the mechanical properties of their dominant mineral phases.