Work performed:
1. I have produced scaffolds with two types of pore orientations: isotropic and anisotropic.
2. I have studied the scaffold pore architecture using scanning electron microscopy (SEM).
3. I have produced 3D images of the scaffolds using high resolution X-ray computed tomography (micro-CT) . In collaboration with other researchers at Cambridge University, a code has been developed to characterise the complex 3D pore structure of the scaffolds (pore diameter, porosity, pore orientation, specific surface area).
4. I have measured the scaffold specific permeability (resistance to fluid flow) using a constant pressure gradient method.
5. I have assessed cell performance in two tissue engineering models: scaffold pre-vascularisation (microvessel-like formation within the scaffolds) and bone formation, investigating the following parameters:
• The migration and distribution of human umbilical cord endothelial cells (HUVECs) within the scaffolds.
• Self-assembly of HUVECs, in a mono-and a co-culture with human osteoblasts (HObs), into microvessel-like structures as a function of scaffold pore architecture.
• HOb viability, metabolic activity, proliferation and osteogenic differentiation as a function of scaffold pore architecture.
Results overview:
I have characterised the scaffold pore architecture using a customised code developed in collaboration with other colleagues at Cambridge University. I have shown that cells were able to go at higher depths and were more uniformly distributed within aligned (anisotropic) scaffolds as compared to isotropic scaffolds. Aligned scaffolds were a better platform for blood vessel cells to self-organise into vascular-like structures, especially when grown in co-culture with supporting cells. These structures, comprised of multiple blood vessel cells attached to one another, were aligned around the pores, and had features resembling native small blood vessels. Additionally, I have found that in the bone model cell activity was higher in the anisotropic scaffolds. Moreover, the premature bone cells seeded on the anisotropic scaffolds showed earlier and stronger differentiation (became more bone-like) as compared to the isotropic ones and produced mineral matrix similarly to the cells in the native bone. Overall, I was able to show that scaffolds pore structure affects the formation of bone and vessel-like structures, and thus needs to be taken into consideration when designing engineered tissues.
Results exploitation and dissemination:
A manuscript on ‘’Collagen scaffolds with tailored pore geometry for building 3-dimnsional vascular networks’’ has recently been accepted in the Materials Letters journal.
A second manuscript on scaffold characterisation (pore architecture, Young’s modulus and specific permeability) and bone formation is under preparation.
The results have been presented in 7 international conferences (e.g. Biologic Scaffolds for Regenerative Medicine International Symposium, Tissue Engineering and Regenerative Medicine International Society World Congress, International Conference on Tissue Engineering and Regenerative Medicine where I was a keynote speaker, and others), arousing great interest in the scientific community.
