Metastatic tumours are complex ecosystems; a community of multiple cell types, including cancerous cells, fibroblasts, and immune cells that exist within a supportive and specific microenvironment. The interplay of these cells, together with tissue specific chemical, structural and temporal signals within a three-dimensional (3D) habitat, direct tumour cell behavior, a subtlety that can be easily lost in 2D tissue culture. Here, we investigate a significantly improved tool, consisting of a novel matrix of functionally programmed peptide sequences, self-assembled into a scaffold to enable the growth and the migration of multicellular lung tumour spheroids, as proof-of-concept.
View Article and Find Full Text PDFFor decades, the study of tissue-engineered skeletal muscle has been driven by a clinical need to treat neuromuscular diseases and volumetric muscle loss. The in vitro fabrication of muscle offers the opportunity to test drug-and cell-based therapies, to study disease processes, and to perhaps, one day, serve as a muscle graft for reconstructive surgery. This study developed a biofabrication technique to engineer muscle for research and clinical applications.
View Article and Find Full Text PDFThe debilitating effects of muscle damage, either through ischemic injury or volumetric muscle loss (VML), can have significant impacts on patients, and yet there are few effective treatments. This challenge arises when function is degraded due to significant amounts of skeletal muscle loss, beyond the regenerative ability of endogenous repair mechanisms. Currently available surgical interventions for VML are quite invasive and cannot typically restore function adequately.
View Article and Find Full Text PDFSynthetic materials designed for improved biomimicry of the extracellular matrix must contain fibrous, bioactive, and mechanical cues. Self-assembly of low molecular weight gelator (LMWG) peptides Fmoc-DIKVAV (Fmoc-aspartic acid-isoleucine-lysine-valine-alanine-valine) and Fmoc-FRGDF (Fmoc-phenylalanine-arginine-glycine-aspartic acid-phenylalanine) creates fibrous and bioactive hydrogels. Polysaccharides such as agarose are biocompatible, degradable, and non-toxic.
View Article and Find Full Text PDFSelf-assembling peptides (SAPs) are a relatively new class of low molecular weight gelators which immobilize their solvent through the spontaneous formation of (fibrillar) nanoarchitectures. As peptides are derived from proteins, these hydrogels are ideal for use as biocompatible scaffolds for regenerative medicine. Importantly, due to the propensity of peptide sequences to act as signals in nature, they are easily functionalized to be cell instructive via the inclusion of bioactive epitopes.
View Article and Find Full Text PDFFor decades, electrode-tissue interfaces are pursued to establish electrical stimulation as a reliable means to control neuronal cells behavior. However, spreading of electrical currents in tissues limits its spatial precision. Thus, optical cues, such as near-infrared (NIR) light, are explored as alternatives.
View Article and Find Full Text PDFThe material properties of natural tissues, such as skeletal muscle, are highly sophisticated and are synthetically challenging to mimic. Using natural biomacromolecules to functionalize self-assembled peptide (SAP) hydrogels has the potential to increase the utility of these materials by more closely reproducing the natural cellular environment. Here, to demonstrate that a conserved co-assembly pathway can retain distinct function, the biocompatible peptide derivative Fmoc-FRGDF was co-assembled with either a sulfated polysaccharide, fucoidan, or the provisional matrix proteoglycan, versican.
View Article and Find Full Text PDFThe ability to fabricate artificial tissue constructs through the controlled organisation of cells, structures and signals within a biomimetic scaffold offers significant promise to the field of regenerative medicine, drug delivery and tissue engineering. Advances in additive manufacturing technologies have facilitated the printing of spatially defined cell-laden artificial tissue constructs capable of providing biomimetic spatiotemporal presentation of biological and physical cues to cells in a designed multicomponent structure. Despite significant progress in the field of bioprinting, a key challenge remains in developing and utilizing materials that can adequately recapitulate the complexities of the native extracellular matrix on a nanostructured, chemical level during the printing process.
View Article and Find Full Text PDFEnabling control over macromolecular ordering and the spatial distribution of structures formed via the mechanisms of molecular self-assembly is a challenge that could yield a range of new functional materials. In particular, using the self-assembly of minimalist peptides, to drive the incorporation of large complex molecules will allow a functionalization strategy for the next generation of biomaterial engineering. Here, for the first time, we show that co-assembly with increasing concentrations of a highly charged polysaccharide, fucoidan, the microscale ordering of Fmoc-FRGDF peptide fibrils and subsequent mechanical properties of the resultant hydrogel can be easily and effectively manipulated without disruption to the nanofibrillar structure of the assembly.
View Article and Find Full Text PDFMicrofluidic systems enable rapid diagnosis, screening and monitoring of diseases and health conditions using small amounts of biological samples and reagents. Despite these remarkable features, conventional microfluidic systems rely on bulky expensive external equipment, which hinders their utility as powerful analysis tools outside of research laboratories. 'Self-contained' microfluidic systems, which contain all necessary components to facilitate a complete assay, have been developed to address this limitation.
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