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3D Bioprinting of immunocompetent skin equivalents for wound healing


   Department of Materials

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  Dr Marco Domingos, Prof Sarah Cartmell  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

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 Chronic wounds are a significant global problem, causing patient morbidity and a substantial financial burden on health services worldwide. The incidence of chronic wounds is currently rising because those populations most susceptible, the elderly and diabetic, are rapidly expanding. In 2018, the annual NHS spend on wound care was estimated at £8.3 billion, while in the U.S. an estimated US$25 billion is spent on their treatment.

Approximately 40-60% of chronic wounds do not heal within 3 months and require more advanced wound therapies such as collagen-based dressings to regulate excess inflammation. Currently, the development of such therapies is reliant on the use of 2D/3D organotypic models that fail to replicate the complex structural and functional organization of native skin, leading to poor research and clinical outcomes. Animal models, including porcine and mice, are often used as an alternative/complementary system to simplistic 2D/3D cell culture models, but present several drawbacks: 1) expensive; 2) limited chronic wound models (porcine); 3) limited physiological relevance to human conditions (mice).

Operating in a layer-by-layer fashion, 3D Bioprinting allows for the precise spatial deposition of cells and materials into 3D constructs, thus opening new opportunities for the development of biomimetic tissue equivalents. Here we aim to combine our expertise in advanced materials, biofabrication and bioreactors to develop a physiologically relevant 3D skin model. The successful candidate will build on existing models and establish new strategies for the generation of stratified, multicellular (e.g. fibroblasts, keratinocytes) and immunocompetent surrogates, to interrogate pathophysiological mechanisms underpinning skin repair.

Main questions to be answered:

  1. Is it possible to successfully include immune cell in a 3D wound model to create a fully physiological model? The student will investigate different strategies to include immune cells (e.g. neutrophils, monocytes, T cells, dendritic cells) into a 3D bioprinted skin model and compare the immunocompetent performance against in vivo models to validate its physiological relevance.
  2. How is the function of immune cells affected by the healing process? Differentiation of monocytes into macrophages during wound healing as well as their correct phenotype expression/maintenance will be investigated through different biological assays to ensure a correct transition from pro-inflammatory to pro-resolving stage.
  3. Are the cells working synergistically to achieve physiological healing? Utilising established in vitro and in silico tools the student will investigate the ability of the model to mimic the native skin tissue niche and support the cellular cross-talk. The performance of the proposed model will eventually be assessed against other commercial available systems from 3M and competitor collagen dressings.
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