Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue

Here, we present an approach to model and adapt the mechanical regulation of morphogenesis that uses contractile cells as sculptors of engineered tissue anisotropy in vitro. Our method uses heterobifunctional cross-linkers to create mechanical boundary constraints that guide surface-directed sculpting of cell-laden extracellular matrix hydrogel constructs. Using this approach, we engineered linearly aligned tissues with structural and mechanical anisotropy. A multiscale in silico model of the sculpting process was developed to reveal that cell contractility increases as a function of principal stress polarization in anisotropic tissues. We also show that the anisotropic biophysical microenvironment of linearly aligned tissues potentiates soluble factor-mediated tenogenic and myogenic differentiation of mesenchymal stem cells. The application of our method is demonstrated by (i) skeletal muscle arrays to screen therapeutic modulators of acute oxidative injury and (ii) a 3D microphysiological model of lung cancer cachexia to study inflammatory and oxidative muscle injury induced by tumor-derived signals.

A Flux-Limited Model for Glioma Patterning with Hypoxia-Induced Angiogenesis

We propose a model for glioma patterns in a microlocal tumor environment under the influence of acidity, angiogenesis, and tissue anisotropy. The bottom-up model deduction eventually leads to a system of reaction–diffusion–taxis equations for glioma and endothelial cell population densities, of which the former infers flux limitation both in the self-diffusion and taxis terms. The model extends a recently introduced (Kumar, Li and Surulescu, 2020) description of glioma pseudopalisade formation with the aim of studying the effect of hypoxia-induced tumor vascularization on the establishment and maintenance of these histological patterns which are typical for high-grade brain cancer. Numerical simulations of the population level dynamics are performed to investigate several model scenarios containing this and further effects.

Control of crystallographic orientation by metal additive manufacturing process of β-type Ti alloys based on the bone tissue anisotropy

Variation in the scanning strategy for β-type Ti alloys during additive manufacturing (AM) enables the fabrication of a singlecrystal-like microstructure possessing a crystallographic texture, in which the low-Young’s modulus-<100> direction is aligned along a specific direction. Thus, metal biomaterial with low elasticity, comparable to the bone Young’s modulus, can be developed by AM, which will contribute to suppress the stress shielding of bone and prevent degradation of bone tissue anisotropy.