Bradley, Mark

Mackay, Logan

Conde González, Antonio David

European Research Council

2020-05-01T14:40:03Z

2020-05-01T14:40:03Z

2020-06-25

The field of functional biomaterials has seen huge progression with enormous efforts made to discover 3D scaffolds that support and promote tissue formation. Polymerbased 3D scaffolds are used extensively as a consequence of their remarkable tunability and biocompatibility. However, the scope of possible scaffolds, with respect to their physical and chemical properties, is vast encompassing chemical composition, wettability, 3D structure and mechanical properties to name but a few. In addition, the combined effects of these properties on cellular fate, in association with scaffold/protein binding, leads to highly complex systems with numerous processes occurring simultaneously at multiple levels, which hinders a full understanding of the cell–material interface. Therefore, despite huge efforts to understand how the physical and chemical cues of these 3D scaffolds trigger and control cellular behaviour, the effect of these properties on cells remains vague, yet continues to be a key element of tissue engineering. 2D polymer microarrays have been shown to be an efficient high-throughput technology to discover new functional polymers. However, these polymer features lack the necessary 3D structure and morphologies present within tissues. In this thesis, I present the development of a new strategy to fabricate arrays of 3D polymer scaffolds exploiting photo-polymerisation within a crystallisable solvent (dimethyl sulfoxide, DMSO), which serves as a template for the generation of pores. Initial studies involved the identification of suitable polyacrylates that were capable of binding and maintaining human bone osteosarcoma cells (SAOS-2 and MG-63). These were then used to optimise a polymerisation process that maximised the formation of pores in addition to analysing the effect of the solvent on the 3D structure of the scaffolds and their mechanical properties. An array of 24 different 3D polymer features was fabricated and screened with SAOS-2 cells as a proof of concept of the applicability of the array, showing that cell attachment, proliferation and morphology could be controlled by the composition of the scaffolds along with their 3D microstructures. A second project (a collaborative effort with the University of Southampton) used the developed screening platform to identify novel 3D scaffolds that promoted the formation of vascularised bone tissue with 45 different 3D polymer scaffolds (15 different polyacrylates with 3 levels of porosity) and foetal bone marrow stroma cells (FBMSCs). A highly biocompatible scaffold was discovered that promoted osteoblastic phenotype expression and vascularisation - the first time for such phenomena had been observed in polyacrylate scaffolds without externally supplied factors. This was validated ex vivo, with a chick chorioallantoic membrane (CAM), and in vivo, with a subcutaneous mouse model, confirming biocompatibility and the formation of new tissue/vasculature.

https://hdl.handle.net/1842/37033

http://dx.doi.org/10.7488/era/334

en

The University of Edinburgh

A. Conde-González, D. Dutta, R. Wallace, A. Callanan and M. Bradley. Rapid Fabrication and Screening of Tailored Functional 3D Biomaterials. Materials Science and Engineering: C, 2020, 108, 110489

A. Conde-González, M. Glinka, D. Dutta, R. Wallace, D. Norman, A. Callanan, R. O. C. Oreffo and M. Bradley (2019). 3D Porous Growth-factor free Scaffolds Supporting Enhanced Vascularization for Tissue Repair.

L. H. Tucker, A. Conde-González, D. Cobice, G. R. Hamm, R. J. A. Goodwin, C. J. Campbell, D. J. Clarke, C. L. Mackay. MALDI Matrix Application Utilizing a Modified 3D Printer for Accessible High Resolution Mass Spectrometry Imaging. Analytical Chemistry, 2018, 90, 15, 8742-8749

K. Neumann, A. Conde-González, M. Owens, A. Venturato, Y. Zhang, J. Geng, M. Bradley. An Approach to the HighThroughput Fabrication of Glycopolymer Microarrays through Thiol-Ene Chemistry. Macromolecules, 2017, 50, 16, 166026-6031

E. López-Ruiz, S. Venkateswaran, M. Perán, G. Jiménez, S. Pernagallo, J. J. Díaz-Mochón, O. Tura-Ceide, J. Melchor, J. Soto, G. Rus, P. J. Real, M. DiazRicart, A. Conde-González, M. Bradley and J. A. Marchal. Poly(ethylmethacrylate-codiethylaminoethyl acrylate) coating improves endothelial repopulation, bio-mechanical and anti-thrombogenic properties of decellularized carotid arteries for blood vessel replacement. Scientific Reports, 2017, 7, 1, 407-420.

functional polymeric biomaterials

biofunctional polymers

3D scaffolds

porous scaffold

vascularisation promotion

Arrays of 3D polymer scaffolds for biomedical applications

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy