Well-defined Thermoresponsive Polymers as Injectable Gels Dr Theoni K. Georgiou Department of Materials, ICL

Group Transfer Polymerisation + Living polymerisation technique  control of the polymer’s molecular weight, composition and architecture + Easy, Fast, Cost effective (RT and higher concentration) + Developed by DuPont to produce specialised polymers - Can only use methacrylate and acrylate monomers with R not being an acid or alcohol group Limitation: degree of polymerisation < 200 (depending on monomer) Webster, O. W. et al J. Am. Chem. Soc. 1983, 105, 5706-5708. Webster, O.W. Science 1991, 251, 887-893. Webster, O. W. Adv. Polym. Sci. 2004, 167, 1-34.

GTP: Choice of Monomers Hydrophobic Hydrophilic (some depending on the pH or the T) Make your own monomers! Methacryloyl chloride + R-OH 

Well-Defined Polymers Polymers of narrow size distribution with defined composition and architecture Vary the length Vary the composition Vary the architecture Structure/Activity Relationships Vary the polymer’s structure

Injectable Gels Thermoresponsive Gels for Tissue Engineering 37C at body temperature the polymer will form a gel room temperature: polymer + cells in culture medium the polymer/cell mixture will be injected into a wound

Sol-Gel Thermo-transition elastic modulus (G’) viscous modulus (G’’) complex viscosity Sol – Gel Transition G’, G’’, Viscosity Temperature

Thermoresponsive Triblock Copolymers Polymers of different molecular weights, architectures and compositions ABC triblock ABA triblock BAC triblock ACB triblock Random terpolymer

Synthesis of Triblock Copolymers THF TBABB (catalyst) MTS (initiator) PEGMA BuMA BuMA All polymers have a molecular weight distributions, dispersity Mw/Mn < 1.19. During polymerisation the dispersity decreased by increasing the MW as expected for a living polymerisation method. Aqueous properties, self-assembly, micelle size is affected by the molecular weight, the architecture as well as the composition of the polymer.

Effect of MW and Composition 20 wt% BuMA 30 wt% BuMA 40 wt% BMA Effect of MW and Composition 15000 g/mol 10000g/mol 50000g/mol solid, dotted, and dashed lines corresponds to elastic modulus G’, viscous modulus G’’ and viscous viscosity Ward, M. A.; Georgiou, T. K. Soft Matter 2012, 8, 2727-2745.

Effect of Architecture ABC ACB BAC cmc Non-ionic hydrophilic Non-ionic hydrophobic Hydrophilic, pH- and thermo-responsive multicompartment hydrogel ?

Effect of Architecture and Alkyl Side Group The ABC is the “best” architecture – best sol-gel transition Increasing the length of the side alkyl group lowers the gel point. The gel stability is decreased with increasing the length of the side alkyl group. solid, dotted, and dashed lines corresponds to elastic modulus G’, viscous modulus G’’ and viscous viscosity Ward, M. A.; Georgiou, T. K. Polym. Chem. 2013, 4(6), 1893-1902.

Does Asymmetry Matter? Gels point decreases when: The hydrophobic content increases The triblock copolymers is more symmetric i.e. when the hydrophobic block ratio approaches one. Ward, M. A.; Georgiou, T. K. J. Polym. Sci., Part A: Polym. Chem. 2013, 51(13), 2850–2859.

Summary of Main Results Aim: Fabrication of thermo-responsive triblock polymers and investigation of how the different characteristics of the polymer affect the thermoresponsive behaviour. T-response molecular weight 7000 g mol-1 30-35 wt% T-response ↑ length  ↓ gel point & stability T-response T-response composition wt% hydrophobic architecture length of hydrophobic side group Ward, M. A.; Georgiou, T. K. J. Polym. Sci.: Part A: Polym. Chem. 2010, 48, 775-783. Ward, M. A.; Georgiou, T. K. Soft Matter 2012, 8, 2727-2745. Ward, M. A.; Georgiou, T. K. Polym. Chem. 2013, 4(6), 1893-1902. Ward, M. A.; Georgiou, T. K. J. Polym. Sci., Part A: Polym. Chem. 2013, 51(13), 2850–2859.

Current Investigations Studying how the PEG side group can affect the thermoresponsive properties. Increase the side group  the gelation point. Studying how the number of blocks can affect the physical chemical properties and the thermoresponsive properties. Investigating if these gels can be used in 3-D printing (both pH and temperature can trigger the gel formation)

Acknowledgments Thank you Funding: University of Hull Engineering and Physical Science Research Council (EPSRC) Royal Society (RS) Department of Materials, Imperial College London Students: Mr Mark Ward Miss Anna Constantinou Thank you