Machine Learned Composite Methods for Electronic Structure Theory.

Because of the prohibitive scaling of ab initio techniques for modeling chemical species with high accuracy, they are not generally tractable for large systems. It is therefore of considerable interest to develop high-accuracy computational models with low computational cost that can afford predictions of electronic structure and properties of macromolecular species. Composite methods, as first introduced by Pople [Pople, J.

Hierarchical biofabrication of biomimetic collagen-elastin vascular grafts with controllable properties via lyophilisation.

This article describes the development of a hierarchical biofabrication technique suitable to create large but complex structures, such as vascular mimicking grafts, using facile lyophilisation technology amenable to multiple other biomaterial classes. The combination of three fabrication techniques together, namely solvent evaporation, lyophilisation, and crosslinking together allows highly tailorable structures from the microstructure up to the macrostructure, and with the ability to independently crosslink each layer it allows great flexibility to match desired native mechanical properties independently of the micro/macrostructure. We have demonstrated the flexibility of this biofabrication technique by independently optimising each of the layers to create a multi-layered arterial structure with tailored architectural and biophysical/biochemical properties using a collagen-elastin composite.

Material stiffness influences the polarization state, function and migration mode of macrophages.

Biomaterial implantation is followed by an inflammatory cascade dominated by macrophages, which determine implant acceptance or rejection through pro- and anti-inflammatory polarization states (Anderson et al., 2008; Brown and Badylak, 2013). It is known that chemical signals such as bacterial endotoxins and cytokines (IL4) can direct macrophage polarization (Mantovani et al.

Identification of stiffness-induced signalling mechanisms in cells from patent and fused sutures associated with craniosynostosis.

Craniosynostosis is a bone developmental disease where premature ossification of the cranial sutures occurs leading to fused sutures. While biomechanical forces have been implicated in craniosynostosis, evidence of the effect of microenvironmental stiffness changes in the osteogenic commitment of cells from the sutures is lacking. Our aim was to identify the differential genetic expression and osteogenic capability between cells from patent and fused sutures of children with craniosynostosis and whether these differences are driven by changes in the stiffness of the microenvironment.

Identification of the mechanisms by which age alters the mechanosensitivity of mesenchymal stromal cells on substrates of differing stiffness: Implications for osteogenesis and angiogenesis.

Unlabelled: In order to identify the mechanisms by which skeletal maturity alters the mechanosensitivity of mesenchymal stromal cells (MSCs) and, the implications for osteogenesis and angiogenesis during bone formation, we compared the response of MSCs derived from children and skeletally-mature healthy adults cultured on soft and stiff collagen-coated polyacrylamide substrates. MSCs from children were more mechanosensitive, showing enhanced angiogenesis and osteogenesis on stiff substrates as indicated by increased endothelial tubule formation, PGF production, nuclear-translocation of YAP, ALP activity and mineralisation. To examine these mechanisms in more detail, a customised PCR array identified an age-dependent, stiffness-induced upregulation of NOX1, VEGFR1, VEGFR2, WIF1 and, of particular interest, JNK3 in cells from children compared to adults.

The effect of time-dependent deformation of viscoelastic hydrogels on myogenic induction and Rac1 activity in mesenchymal stem cells.

Cell behaviours within tissues are influenced by a broad array of physical and biochemical microenvironmental factors. Whilst 'stiffness' is a recognised physical property of substrates and tissue microenvironments that influences many cellular behaviours, tissues and their extracellular matrices are not purely rigid but 'viscoelastic' materials, composed of both rigid-like (elastic) and dissipative (viscous) elements. This viscoelasticity results in materials displaying increased deformation with time under the imposition of a defined force or stress, a phenomenon referred to as time-dependent deformation or 'creep'.

Effects of bound versus soluble pentosan polysulphate in PEG/HA-based hydrogels tailored for intervertebral disc regeneration.

Previous reports in the literature investigating chondrogenesis in mesenchymal progenitor cell (MPC) cultures have confirmed the chondro-inductive potential of pentosan polysulphate (PPS), a highly sulphated semi-synthetic polysaccharide, when added as a soluble component to culture media under standard aggregate-assay conditions or to poly(ethylene glycol)/hyaluronic acid (PEG/HA)-based hydrogels, even in the absence of inductive factors (e.g. TGFβ).

An injectable hydrogel incorporating mesenchymal precursor cells and pentosan polysulphate for intervertebral disc regeneration.

Intervertebral disc (IVD) degeneration is one of the leading causes of lower back pain and a major health problem worldwide. Current surgical treatments include excision or immobilisation, with neither approach resulting in the repair of the degenerative disc. As such, a tissue engineering-based approach in which stem cells, coupled with an advanced delivery system, could overcome this deficiency and lead to a therapy that encourages functional fibrocartilage generation in the IVD.

The influence of substrate creep on mesenchymal stem cell behaviour and phenotype.

Human mesenchymal stem cells (hMSCs) are capable of probing and responding to the mechanical properties of their substrate. Although most biological and synthetic matrices are viscoelastic materials, previous studies have primarily focused upon substrate compressive modulus (rigidity), neglecting the relative contributions that the storage (elastic) and loss (viscous) moduli make to the summed compressive modulus. In this study we aimed to isolate and identify the effects of the viscous component of a substrate on hMSC behaviour.

Complex embryos displaying bilaterian characters from Precambrian Doushantuo phosphate deposits, Weng'an, Guizhou, China.

Three-dimensionally preserved embryos from the Precambrian Ediacaran Doushantuo Formation, Weng'an, Guizhou, southern China, have attracted great attention as the oldest fossil evidence yet found for multicellular animal life on Earth. Many embryos are early cleavage embryos and most of them yield a limited phylogenetic signal. Here we report the discovery of two Doushantuo embryos that are three-dimensionally preserved and complex.

Germ line determinants are not localized early in sea urchin development, but do accumulate in the small micromere lineage.

Two distinct modes of germ line determination are used throughout the animal kingdom: conditional-an inductive mechanism, and autonomous-an inheritance of maternal factors in early development. This study identifies homologs of germ line determinants in the sea urchin Strongylocentrotus purpuratus to examine its mechanism of germ line determination. A list of conserved germ-line associated genes from diverse organisms was assembled to search the S.