3DSTAR · Highly porous collagen scaffolds for building 3D vascular networks: structure and property relationships
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-11-14 → 2018-11-13
- EU contribution
- €195,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Highly porous collagen scaffolds for building 3D vascular networks: structure and property relationships
In many diseases and traumas, organ function is severely compromised, and the only solution is organ transplantation. There are two major problems associated with this strategy: a shortage of organs for transplantation and an immunological mismatch between the donor and the recipient, leading to organ rejection. If we could restore organ function by growing it in the lab from patient’s own cells, we’d be able to avoid both afore-mentioned problems. To do so, cells must be grown under tissue-specific conditions in order to reproduce the right numbers and activity. In my project, I have addressed the question of finding the right spatial conditions to grow bone and microvasculature. I have produced scaffolds suitable for growing cells in a 3-dimentional (3D) microenvironment. These scaffolds are made of a biocompatible, bioactive material and have high porosity. This allows cells to get deep within the scaffolds, attach and start producing the tissue of interest. The overall objectives were to characterise the complex 3D pore structure of these scaffolds (size, shape and interconnectivity), to establish how pore architecture affects cell performance and identify the right cell culture conditions (cell density, co-culture with other cells, etc) to encourage cells to form vascular-like structures and bone. I have investigated two types of pore configurations: randomly aligned (isotropic) or unidirectionally aligned (anisotropic) and have assessed how this pore alignment affects the way cells attach and grow, and how they start producing the engineered tissue. To conclude, I have identified the optimal conditions to grow both bone and micro-vessel tissues by investigating two main parameters: what cell types to include and which pore geometry is best. I have shown that anisotropic scaffolds are preferable for the formation of bone and micro-vessels, and that growing blood vessel cells together with growth supporting cells promote better scaffold vascularisation. Addressing these questions gives a better understanding of the optimum conditions to grow these two tissues, and thus will help to grow the whole bone and other vascularised organs in the future. This will eliminate the need for donor organs and will prevent organ rejection, thereby saving lives and improving the quality of life of many people.
Data: CORDIS, © European Union
Project objective
This proposal concerns with the development of functional 3D hierarchical vasculature within engineered freeze-dried collagen scaffolds. The main objective is to investigate the contribution of scaffold’s pore architecture (size, shape and interconnectivity) and culture conditions, such as cell ratios in co-culture, perfusion vs. static culture and hypoxia, on the self-organisation of endothelial cells into vascular-like structures. A comprehensive 2-year, highly inter-disciplinary programme is planned encompassing processing, scaffold structure characterisation, structure-property investigation and systematic in vitro experimentation. The in vitro work will be carried out in collaboration with the REPAIR-lab in Mainz, Germany - a founding member of the European Commission Network of Excellence EXPERTISSUES. Freeze-drying process parameters will be varied to produce isotropic and anisotropic scaffolds, with pore sizes mimicking native small blood vessels. The pore architecture, in both dry and hydrated states, will be quantified via X-ray tomography and 2-photon confocal microscopy, respectively, using original methodologies. The Young’s modulus and resistance to fluid flow (permeability) of scaffolds will be measured as a function of pore architecture characteristics. A customised set-up allowing low strain measurements of Young’s modulus will be used to establish whether conventional mechanical testing is suitable. Fluid permeability will be measured by applying a constant pressure gradient. Rather surprisingly in view of permeability’s significance in nutrient diffusion and waste removal, there is only a single study on permeability. Vascular organization, maturation and functionality of optimised scaffolds will be studied as a function of pore architecture, using state-of-the-art microscopy, real-time imaging, perfusion tests, histology and a variety of biochemical assays.
Original text from CORDIS.
Participants
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGECoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union
