Silicone elastomers : from fast curing to biomedical applications Khai D. Q. Nguyen, Dexu Kong, William V. Megone, Lihui Peng, Julien Gautrot RIEG afternoon meeting 23 rd March 2018
Biomaterials designs Bioengineering Cell sensing behaviour
Cross-linking chemistry : thiol-ene, condensation, UV / visible light activation Biomaterial design and synthesis Chemistry Properties Applications Cure speed, cure depth Control of mechanical properties Interface mechanics 3D printing, Microfabrication Microfluidics Conductive silicone Coatings Cell culture
Where can we find Silicone?
Curing chemistries of Silicones Radical Free radical mechanism Temperature is necessary Catalyst: organic peroxides Addition Hydrosilylation reaction Catalyst: Pt, Pd, or Rh salts or their complexes. Condensation Condensation between hydroxy-pdms and multifunctional silane Moisture is necessary Catalyst: organometallic reagent and metal salts
Why a new novel curing chemistry necessary? Drawback of current curing chemistries: - High-temperature with a need for post-cure step (Radical) - Toxic metal-based catalysts and relatively slow curing process (Addition and Condensation) Absorption of proteins, bacteria, and other biomolecules - Device failure, infection Low surface tension : - Difficult to adhere to other materials (e.g. glass, hydrogels) - Requires surface activation (e.g. plasma treatment) or specific functionalisation strategies. Fast curing under mild conditions Controlling surface chemistry to perform post-functionalisation without structural damages
Thiol-ene chemistry for silicone Attractive features: - Efficient cure at ambient temperature - No need of metal catalyst - Less sensitive to oxygen inhibition - Good tolerance of wide range of functionalities Motor Hoyle, C. E., Bowman, C. N., Angew. Chem. Int. Ed, 2010, 49, 1540. Nguyen et al., Polymer chemistry, 2016, 7, 5281. TA Instrument Ltd.
In-situ photorheology Gelation point UV exposure t gel Nguyen et al., Polymer chemistry, 2016, 7, 5281.
Storage Modulus / Pa Control of mechanical properties of PDMS network 100,000 10,000 1,000 100 10 1:1 1:1.5 1:2 1:2.5 1:3 30 32 34 36 38 Time / s Rapid reaction (less than 2s) Mechanical properties of network controlled effectively by ene:thiol ratio Reaction rate increases with increasing thiol- content Nguyen et al., Polymer chemistry, 2016, 7, 5281.
The impact of viscosity Relatively comparable storage moduli of cross-linked networks. Great potential for 3D printing of soft-material-based devices. Diffusion controlled characteristic. Nguyen et al., Polymer chemistry, 2016, 7, 5281.
The impact of UV irradiance Significantly affect the gelation time Only slight variation of cross-linked network. Nguyen et al., Polymer chemistry, 2016, 7, 5281.
% live Cytocompatibility With Collagen Without Collagen Low stiffness (5 kpa) 100 80 60 40 20 10μm 0 Plastic High stiffness PDMS Low stiffness PDMS High stiffness (126 kpa) Good cell survival. Cell adhesion revealing the structured stress fibres. 10μm Nguyen et al., Polymer chemistry, 2016, 7, 5281.
Promoting the adhesion of silicone to glass surface A Master B Glass substrate Plasma treatment Surface functionalisation with acrylate/vinyl silane C Bonding via UV irradiation
In-situ SEM Deben 200N tensile rig Glass side PDMS side Nguyen et al., Polymer chemistry, 2016, 7, 5281.
Potential applications 3D matrices for organ-on-chip 3D printing Silicone layer to promote bonding & biofunctionlisation Biofunctionalisation of silicone substrates
Silicone in cell culture Pelham and Wang, PNAS, 94, 1997 Engler et al., Cell, 126, 2006 Kong, Nguyen et al. Faraday Discussions, 204, 2017 Trappmann, Gautrot et al. Nature Mater. 2012
Cell growth on a liquid/liquid interface Kong, Nguyen et al. Nano Letters, 18, 2018
Conclusion Fast and efficient cross-linking of PDMS under mild condition via thiol-ene chemistry with tailored mechanical properties of silicone network. Great potential for 3D printing and microfabrication applications. Non-destructive approach to fabricate microfluidic devices and embed hydrogels in the 3D matrices for organ-on-chip studies. Useful biomaterial system for the culture of cells on silicone substrates with controlled bulk mechanical properties. Cell response at the liquid/liquid interface could lead to exciting applications of silicone molecule designs for elmusion-based 3D bioreactor or cell nanosheet formation.
Acknowledgement The Gautrot Lab: Biointerface for Life Sciences (http://biointerfaces.qmul.ac.uk) FormFormForm Ltd (https://sugru.com) Dr. Dexu Kong Dr. Lewis Tunnicliffe Dr. Burcu Colak Dr. Olivier Picot Dr. Maria Crespo Ribadeneyra William V. Megone Lihui Peng & Others THANK YOU!!! Tom Dowden Steve Westall Mark Buckingham Vivian Christogianni & Others