Development of an microfluidic model to study the role of microenvironmental cells in oral cancer metastasis.

Metastasis occurs when cancer cells leave the primary tumour and travel to a secondary site to form a new lesion. The tumour microenvironment (TME) is recognised to greatly influence this process, with for instance the vascular system enabling the dissemination of the cells into other tissues. However, understanding the exact role of these microenvironmental cells during metastasis has proven challenging.

Vascularised cardiac spheroids-on-a-chip for testing the toxicity of therapeutics.

Microfabricated organ-on-a-chips are rapidly becoming the gold standard for the testing of safety and efficacy of therapeutics. A broad range of designs has emerged, but recreating microvascularised tissue models remains difficult in many cases. This is particularly relevant to mimic the systemic delivery of therapeutics, to capture the complex multi-step processes associated with trans-endothelial transport or diffusion, uptake by targeted tissues and associated metabolic response.

The impact of pericytes on the stability of microvascular networks in response to nanoparticles.

Recapitulating the normal physiology of the microvasculature is pivotal in the development of more complex in-vitro models and organ-on-chip designs. Pericytes are an important component of the vasculature, promoting vessel stability, inhibiting vascular permeability and maintaining the vascular hierarchical architecture. The use of such co-culture for the testing of therapeutics and nanoparticle safety is increasingly considered for the validation of therapeutic strategies.

Design of an Integrated Microvascularized Human Skin-on-a-Chip Tissue Equivalent Model.

Tissue-engineered skin constructs have been under development since the 1980s as a replacement for human skin tissues and animal models for therapeutics and cosmetic testing. These have evolved from simple single-cell assays to increasingly complex models with integrated dermal equivalents and multiple cell types including a dermis, epidermis, and vasculature. The development of micro-engineered platforms and biomaterials has enabled scientists to better recreate and capture the tissue microenvironment , including the vascularization of tissue models and their integration into microfluidic chips.

Multi-Scale Analysis of the Composition, Structure, and Function of Decellularized Extracellular Matrix for Human Skin and Wound Healing Models.

The extracellular matrix (ECM) is a complex mixture of structural proteins, proteoglycans, and signaling molecules that are essential for tissue integrity and homeostasis. While a number of recent studies have explored the use of decellularized ECM (dECM) as a biomaterial for tissue engineering, the complete composition, structure, and mechanics of these materials remain incompletely understood. In this study, we performed an in-depth characterization of skin-derived dECM biomaterials for human skin equivalent (HSE) models.

Photoconfigurable, Cell-Remodelable Disulfide Cross-linked Hyaluronic Acid Hydrogels.

Dynamic photoresponsive synthetic hydrogels offer important advantages for biomaterials design, from the ability to cure hydrogels and encapsulate cells to the light-mediated control of cell-spreading and tissue formation. We report the facile and effective photocuring and photoremodeling of disulfide-cross-linked hyaluronic acid hydrogels, based on photo-oxidation of corresponding thiol residues and their radical-mediated photodegradation. We find that the mechanical properties of disulfide hydrogels and the extent of their photoremodeling can be tuned by controlling the photo-oxidation and photodegradation reactions, respectively.

Contractile myosin rings and cofilin-mediated actin disassembly orchestrate ECM nanotopography sensing.

The nanotopography and nanoscale geometry of the extra-cellular matrix (ECM) are important regulators of cell adhesion, motility and fate decision. However, unlike the sensing of matrix mechanics and ECM density, the molecular processes regulating the direct sensing of the ECM nanotopography and nanoscale geometry are not well understood. Here, we use nanotopographical patterns generated via electrospun nanofibre lithography (ENL) to investigate the mechanisms of nanotopography sensing by cells.

Stem Cell Expansion and Fate Decision on Liquid Substrates Are Regulated by Self-Assembled Nanosheets.

The culture of adherent cells is overwhelmingly relying on the use of solid substrates to support cell adhesion. Indeed, it is typically thought that relatively strong bulk mechanical properties (bulk moduli in the range of kPa to GPa) are essential to promote cell adhesion and, in turn, regulate cell expansion and fate decision. In this report, we show that adherent stem cells such as mesenchymal stem cells and primary keratinocytes can be cultured at the surface of liquid substrates and that this phenomenon is mediated by the assembly of polymer nanosheets at the liquid-liquid interface.

Surface-Initiated Poly(oligo(2-alkyl-2-oxazoline)methacrylate) Brushes.

Polymer brushes are particularly performant antifouling coatings, owing to their high grafting density that prevents unwanted biomacromolecules to diffuse through the coating and adhere to the underlying substrate. In addition to this structural feature, polymer brushes require a relatively high level of hydrophilicity and a globally neutral structure to display ultrahigh protein resistance. Poly(2-alkyl-2-oxaolines) are attractive building blocks for such coatings as they can display relatively high hydrophilicity, owing to their amide repeat units, but can also be side-chain and end-chain functionalized relatively readily.

Protein Nanosheet Mechanics Controls Cell Adhesion and Expansion on Low-Viscosity Liquids.

Adherent cell culture typically requires cell spreading at the surface of solid substrates to sustain the formation of stable focal adhesions and assembly of a contractile cytoskeleton. However, a few reports have demonstrated that cell culture is possible on liquid substrates such as silicone and fluorinated oils, even displaying very low viscosities (0.77 cSt).

Biofunctionalized Patterned Polymer Brushes via Thiol-Ene Coupling for the Control of Cell Adhesion and the Formation of Cell Arrays.

Thiol-ene radical coupling is increasingly used for the biofunctionalization of biomaterials. Thiol-ene chemistry presents interesting features that are particularly attractive for platforms requiring specific reactions with peptides or proteins and the patterning of cells, such as reactivity in physiological conditions and photoactivation. In this work, we synthesized alkene-functionalized (allyl and norbornene residues) antifouling polymer brushes (based on poly(oligoethylene glycol methacrylate)) and studied thiol-ene coupling with a series of thiols including cell adhesive peptides RGD and REDV.

Differential integrin expression regulates cell sensing of the matrix nanoscale geometry.

Unlabelled: The nanoscale geometry and topography of the extra-cellular matrix (ECM) is an important parameter controlling cell adhesion and phenotype. Similarly, integrin expression and the geometrical maturation of adhesions they regulate have been correlated with important changes in cell spreading and phenotype. However, how integrin expression controls the nanoscale sensing of the ECM geometry is not clearly understood.

Cell sensing of physical properties at the nanoscale: Mechanisms and control of cell adhesion and phenotype.

Unlabelled: The chemistry, geometry, topography and mechanical properties of biomaterials modulate biochemical signals (in particular ligand-receptor binding events) that control cells-matrix interactions. In turn, the regulation of cell adhesion by the biochemical and physical properties of the matrix controls cell phenotypes such as proliferation, motility and differentiation. In particular, nanoscale geometrical, topographical and mechanical properties of biomaterials are essential to achieve control of the cell-biomaterials interface.