Topic status: We're looking for students to study this topic.
We have previously reported that novel vitronectin:growth factor (VN:GF) complexes significantly increase re-epithelialization in a partial-thickness wounded de-epidermised dermis (DED) 3D human skin equivalent model (HSE). In addition, we have demonstrated that the VN:GF complexes enhance breast epithelial cell migration via increased and sustained activation of the PI3-K/AKT signalling pathway through co-activation of the IGF cell surface receptor and v-integrins. However, these experiments were undertaken in 2-D culture systems. 2-D cell culture systems provide cells with extremely unnatural geometric, mechanical, and biochemical restrictions. This study therefore aims to investigate the underlying mechanisms behind the enhanced wound healing stimulated by VN:GF complexes using 3-D DED-HSE models.
- Aim 1: Investigate the effects of the VN-binding v-integrins, and the insulin-like growth factor receptors (IGF-1R) on keratinocyte stimulated by VN:GF using 3D DED-HSE wound models
- Aim 2: Identify the signal transduction pathways underlying the enhanced wound healing stimulated by VN:GF using the 3D DED-HSE wound models
Methods and techniques that will be developed in the course of this project:
- Isolation and tissue culture of human skin keratinocytes
- Construction of 3D DED-HSE wound model
- Western immunodetection of signalling