Design and manufacture of an antimicrobial multi-layered scaffold for skin regeneration

To apply for this programme, please visit www.advanced-biomedical-materials-cdt.manchester.ac.uk. Informal enquiries are welcome, to [Email Address Removed].

ABM CDT Full thickness skin injuries affect the quality of life of millions of people; they involve the loss of a big amount of tissue and they are normally associated with severe infections, burns or skin cancer surgery. The gold standard treatment is the use of a skin graft (a patch of skin that is normally removed from another area of the patient’s body and then attached to the affected area). Autologous skin grafts are not always available and the use of tissue engineered grafts is needed. Tissue engineering approaches are clinically useful but they also have limitations. Current constructs do not deliver cells under the physiological conditions under which skin cell populations normally exist in the living body; therefore, there is a need for delivering new biomaterial devices that reproduce closely the physical space in which cells exist in the native skin.

Here we propose to create a multifunctional hierarchical membrane by combining the precision of additive manufacturing techniques such as microstereolithography, the porosity offered by PolyHIPE materials and the clinical relevance and industrial scale up enabled by electrospinning. The student working on this project will explore the creation of a smart device which will mimic to a certain extent the structure of the native skin. The construct will combine 3 individual functional scaffolds containing (i) A porous layer with defined topography resembling the skin rete ridges at the dermal epithelial junction (which have shown to improve shear resistance, enhance nutrient diffusion and aid in keratinocyte differentiation); this layer will also incorporate antimicrobial agents (including cerium and Aloe Vera derivatives as well as small sugar molecules); (ii) an electrospun nanofibrous pseudo basement membrane to enhance keratinocyte attachment: (iii) a porous under layer equipped with artificial vasculature to ensure blood supply.

Main questions to be answered:

1. Can we use electrospinning and 3D-printing approaches to create a stable 3-layered construct avoiding delamination and incorporating topographical cues in Layer 1 and artificial channel-like structures in Layer 3? The combination of fibre technology and additive manufacturing using PolyHIPE materials (provided by Dr. Claeyssens) will be key to ensure the hierarchy and stability of the construct.
2. Can we incorporate antimicrobial agents within Layer 1 and test their effectivity on common pathogenic bacteria (e.g., Pseudomonas aeruginosa, Staphylococcus aureus, MRSA) in planktonic and biofilm forms, both in 2D models and in 3D tissue engineered models of skin wound infection?The expertise provided by Dr. Shepherd in this part of the project will be key to identify the right antibacterial agent or combination of agents to incorporate in the construct.
3. Can we induce the formation of rete ridges in an injured skin in vitro model via the incorporation of our multi-layered membranes? Dr. Ortega and her team have recently demonstrated (see ACS publication on list above) that the incorporation of topographical cues within a single-layered electrospun scaffold can aid in the formation of a native-like skin niche structure as well as in the stratification of the skin layers.
4. Can we incorporate a functional vasculature network in Layer 3 to ensure future supply of nutrients and oxygen?The team has expertise in the development of angiogenic materials (see publications above) as well as in the use of the In Ovo Chick Chorioallantoic Membrane (CAM) Assay.

University of Manchester, Department of Materials - 19 PhD Projects Available

University of Sheffield, Department of Materials Science and Engineering, 7 PhD Projects Available