Design, production and evaluation of an auxetic straining device for application in lung tissue engineering scaffolds

One of the main challenges in lung tissue engineering is the replication of the complex structure and mechanics of the native environment. This thesis addresses two main objectives: firstly, the development of biomimetic scaffolds, based on collagen type I, that replicate the porous architecture of the lung parenchyma, and, secondly, the design of a bioreactor system that can apply physiologically relevant mechanical cues to these scaffolds. First, a predictive relationship between the lyophilisation conditions and the resulting pore size of ice-templated collagen scaffolds was established. Systematic variations in the freeze-drying conditions resulted in scaffolds with average pore sizes ranging from 46 μm to 251 μm, closely matching the average lung alveoli size of 79 μm. The concept of heat flux density (HFD) at equilibrium was introduced to quantify latent heat extraction efficiency during freezing and to predict scaffold pore size. A power law relationship was established (with an HFD exponent of – 0.44), and the method provided a non-destructive and non-intrusive approach to pore architecture control. Next, a substrate-straining device was designed to apply controlled mechanical cues to the porous collagen scaffolds. By capitalising on the negative Poisson’s ratio exhibited by auxetic materials, it was possible to translate uniaxial loading into biaxial expansion. Poly-L-lactide and polypropylene re-entrant honeycomb auxetic meshes were 3D-printed and incorporated into collagen scaffolds. Computational simulations were undertaken, and it was predicted that a 0.03 uniaxial tensile strain would induce a 6% increase in the pore volume of the attached scaffold. The experimental data obtained confirmed the simulations. The biaxial straining device was then tested using human dermal fibroblasts seeded in collagen gels. It was found that, after 22 h of straining, the cells exhibited a significant increase in aspect ratio from 1.7 to 2.7 while maintaining a random orientation, indicating the biaxial nature of the applied mechanical cues. It was concluded that the auxetic biaxial straining device offers the potential to apply mechanical cues to a wide range of cell-seeded substrates.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Wei, Gengyao

Advisors dc:contributor.advisor

• Best, Serena
• Cameron, Ruth

• auxetic mesh
• biaxial straining device
• collagen scaffolds
• heat flux density
• lung tissue engineering
• lyophilisation

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/f6ed6a69-fe88-4bf6-ad84-6e45f5741032/download
• https://creativecommons.org/licenses/by/4.0/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.112283

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/374079