Design of A Microfluidics Integrated Skin-on-a-Chip Tissue Model

To design novel "Tissue-On-A-Chip" models of the skin. The research will focus on the development of novel in vitro skin model that can be used for fundamental biological studies as well as drug efficacy or toxicity testing. Such tissue models are important to replace animal models, but also make better prediction of safety and efficacy testing, based on human cells.

Cells cultured on 2D matrices poorly recapitulate the function and phenotype of cells in vivo. To address this issue, new 3D culture systems are being developed, but need interfacing with multiple compartment if the true complexity of tissues is to be captured and to control parameters such as flow and interstitial pressure, perfusion with nutrients, growth factors, cytokines or drugs and simple sampling of secreted factors or metabolites. Microfluidic systems are perfectly suited for this task and offer advantages for imaging of samples and standardisation of procedures. This project will explore the fabrication of microfluidic-based skin models and apply them to the understanding of skin sensitization mechanisms in response to specific chemicals.

This project will develop microfluidic chips loaded with biomimetic hydrogels encapsulating cells, recreating the structure of human skin (dermis and epidermis). Microfabrication of the chips and their characterisation (electron microscopy) will be carried out. The impact of the device architecture on cell behaviour and tissue formation, the dynamics of these processes, the impact of perfusion with growth factors and drugs, and the occurrence of sensitisation will be studied via (live) microscopy, immunostaining, western blotting and qPCR. This project will be integrated with other projects in the Gautrot lab, focusing on the development of biomaterials and biomimetic hydrogels as well as their microfabrication (http://biointerfaces.qmul.ac.uk/), in close collaboration with the Connelly lab, with expertise in skin biology and wound healing models (http://www.blizard.qmul.ac.uk/staff/44-centre-for-cell-biology-and-cutaneous-research/91-connelly-john.html).

The research group has a strong track-record in the field of materials science: their design and synthesis, application as smart materials and biomaterials, microfabrication and study of cell interactions (see Biomaterials 2010, 2012, Nature Materials 2012, Nature Cell Biology 2010 and Integrative Biology 2013, Nano Letters 2014, Acta Biomaterialia 2016).