Mechanotransducive surfaces for enhanced cell osteogenesis, a review.

Novel strategies employing mechano-transducing materials eliciting biological outcomes have recently emerged for controlling cellular behaviour. Targeted cellular responses are achieved by manipulating physical, chemical, or biochemical modification of material properties. Advances in techniques such as nanopatterning, chemical modification, biochemical molecule embedding, force-tuneable materials, and artificial extracellular matrices are helping understand cellular mechanotransduction. Collectively, these strategies manipulate cellular sensing and regulate signalling cascades including focal adhesions, YAP-TAZ transcription factors, and multiple osteogenic pathways. In this minireview, we are providing a summary of the influence that these materials, particularly titanium-based orthopaedic materials, have on cells. We also highlight recent complementary methodological developments including, but not limited to, the use of metabolomics for identification of active biomolecules that drive cellular differentiation.

IĸB Protein BCL3 as a Controller of Osteogenesis and Bone Health.

OBJECTIVE: IĸB protein B cell lymphoma 3-encoded protein (BCL3) is a regulator of the NF-κB family of transcription factors. NF-κB signaling fundamentally influences the fate of bone-forming osteoblasts and bone-resorbing osteoclasts, but the role of BCL3 in bone biology has not been investigated. The objective of this study was to evaluate BCL3 in skeletal development, maintenance, and osteoarthritic pathology. METHODS: To assess the contribution of BCL3 to skeletal homeostasis, neonatal mice (n = 6-14) lacking BCL3 (Bcl3-/- ) and wild-type (WT) controls were characterized for bone phenotype and density. To reveal the contribution to bone phenotype by the osteoblast compartment in Bcl3-/- mice, transcriptomic analysis of early osteogenic differentiation and cellular function (n = 3-7) were assessed. Osteoclast differentiation and function in Bcl3-/- mice (n = 3-5) was assessed. Adult 20-week Bcl3-/- and WT mice bone phenotype, strength, and turnover were assessed. A destabilization of the medial meniscus model of osteoarthritic osteophytogenesis was used to understand adult bone formation in Bcl3-/- mice (n = 11-13). RESULTS: Evaluation of Bcl3-/- mice revealed congenitally increased bone density, long bone dwarfism, increased bone biomechanical strength, and altered bone turnover. Molecular and cellular characterization of mesenchymal precursors showed that Bcl3-/- cells displayed an accelerated osteogenic transcriptional profile that led to enhanced differentiation into osteoblasts with increased functional activity, which could be reversed with a mimetic peptide. In a model of osteoarthritis-induced osteophytogenesis, Bcl3-/- mice exhibited decreased pathological osteophyte formation (P < 0.05). CONCLUSION: Cumulatively, these findings demonstrate that BCL3 controls developmental mineralization to enable appropriate bone formation, whereas in a pathological setting, it contributes to skeletal pathology.

An ossifying landscape: materials and growth factor strategies for osteogenic signalling and bone regeneration.

Breakthroughs in our understanding of the complex interplay between cellular nanoenvironment and biomolecular signalling pathways are facilitating development of targeted osteogenic platforms. As critical biomolecules for osteogenesis, growth factors stimulate osteogenesis by activating key genes and transcription factors. The first half of this review presents emerging interconnectedness and recent discoveries of osteogenic signalling pathways initiating from growth factors for example, bone morphogenetic protein 2 (BMP-2). To complement this, the second half of review proposes a number of strategies to induce osteogenesis which include metallic, organic implants, nanotopological environments as well as growth factor immobilization techniques. The drawbacks of traditional osteogenic implants and how these have been overcome by biomedical engineers in the recent years without producing side-effects have also been summarized.

Helical ordering of envelope-associated proteins and glycoproteins in respiratory syncytial virus.

Human respiratory syncytial virus (RSV) causes severe respiratory illness in children and the elderly. Here, using cryogenic electron microscopy and tomography combined with computational image analysis and three-dimensional reconstruction, we show that there is extensive helical ordering of the envelope-associated proteins and glycoproteins of RSV filamentous virions. We calculated a 16 Å resolution sub-tomogram average of the matrix protein (M) layer that forms an endoskeleton below the viral envelope. These data define a helical lattice of M-dimers, showing how M is oriented relative to the viral envelope. Glycoproteins that stud the viral envelope were also found to be helically ordered, a property that was coordinated by the M-layer. Furthermore, envelope glycoproteins clustered in pairs, a feature that may have implications for the conformation of fusion (F) glycoprotein epitopes that are the principal target for vaccine and monoclonal antibody development. We also report the presence, in authentic virus infections, of N-RNA rings packaged within RSV virions. These data provide molecular insight into the organisation of the virion and the mechanism of its assembly.

Customizable 3D Printed 'Plug and Play' Millifluidic Devices for Programmable Fluidics.

Three dimensional (3D) printing is actively sought after in recent years as a promising novel technology to construct complex objects, which scope spans from nano- to over millimeter scale. Previously we utilized Fused deposition modeling (FDM)-based 3D printer to construct complex 3D chemical fluidic systems, and here we demonstrate the construction of 3D milli-fluidic structures for programmable liquid handling and control of biological samples. Basic fluidic operation devices, such as water-in-oil (W/O) droplet generators for producing compartmentalized mono-disperse droplets, sensor-integrated chamber for online monitoring of cellular growth, are presented. In addition, chemical surface treatment techniques are used to construct valve-based flow selector for liquid flow control and inter-connectable modular devices for networking fluidic parts. As such this work paves the way for complex operations, such as mixing, flow control, and monitoring of reaction / cell culture progress can be carried out by constructing both passive and active components in 3D printed structures, which designs can be shared online so that anyone with 3D printers can reproduce them by themselves.