Functional materials from cellulose: tissue scaffolds, formulation - - PowerPoint PPT Presentation

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Functional materials from cellulose: tissue scaffolds, formulation ingredients and printed materials

Janet L. Scott ChemSpec June 2016, Basel

… or how to turn into

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• 1. delicate cellulose hydrogel based scaffolds for

tissue engineering;

• 2. particu​late rheology modifiers and emulsion

stabilisers that are effective at low weight percent inclusion in aqueous (and other) formulations; and

• 3. robust, flame r​etardant composites in a range
• f formats from beads to sheets.

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Cellulose based scaffolds for tissue engineering

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Cellulose as a tissue scaffold material?

• Biocompatible
• Foreign body reaction is relatively mild1
• Oxidised cellulose is bioresorbable2
• Not animal derived
• No opportunity for contamination, e.g. with prions
• Doesn’t offend religious or personal sensibilities
• Can be formed into scaffolds
• Films (2D) / Hydrogels and sculpted shapes (3D)

1.

• T. Miyamoto, et al., J. Biomed. Mat. Res., 1989, 23, 125-133

2. US 6500777, Bioresorbable oxidized cellulose composite …, Ethicon, 2002

Challenge: cellulose is a hydrophilic material with low non-specific protein adsorption; mammalian cells do not readily attach to cellulose surfaces

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Cellulose is readily functionalised

Oxidation – negatively charged surface Substitution – positively charged surface

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Characterisation: conductometric titration and ss NMR

[ppm] 1H – 13C CP MAS @ 10 kHz with a contact time of 2000 µs (300 MHz solid –state NMR)

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Cell attachment

400 µm

Cells attached to cationic cellulose

Cell attachment (%) = No. of cells on scaffold Seeding density × 100

Solution: surface modification (cationic) promotes cell attachment without mediation by added proteins

10 20 30 40 50 60 70 80 90 100

Unmodified Cationic Anionic Cell attachment / %

Cellulose films Cellulose films + FBS Cellulose films + RGD

UK Patent Application No. 1607802.4; J.C. Courtenay, M.A. Johns, F. Galembeck, C. Deneke, E.M. Lanzoni, C.A. Costa, J.L. Scott, R.I. Sharma, Biomaterials, 2016, submitted

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Cell spreading on scaffolds

Cationic cellulose = 24h

Blue = cell nucleus Green = cell membrane

Cationic cellulose = 1h

Circularity = 4π (Area)/ (Perimeter)2

0.2 0.4 0.6 0.8 1 Control Unmodified 0.6 DS 4.7 DS 9.2 DS

MG63 cell circularity Scaffold 1h - Circularity 24 h - Circularity

Cell circularity factor = measure of spreading 1 = cell is circular, 0 = cell is spreading

Blue = cell nucleus Green = cell membrane

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Cells attach and spread on cationised cellulose without intervention of proteins or ligands

Cellulose scaffold bearing positive surface charge

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Bacterial cellulose films with modified surfaces

Surface topography inferred from tip amplitude measurements in electrostatic force microscopy (1 µm2 sample)

400 nm 400 nm 400 nm

UK Patent Application No. 1607802.4; J.C. Courtenay, M.A. Johns, F. Galembeck, C. Deneke, E.M. Lanzoni, C.A. Costa, J.L. Scott, R.I. Sharma, Biomaterials, 2016, submitted

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Capacitive coupling (dC/dz)

Unmodified Anionic Cationic

0.0 0.5 1.0 1.5 2.0 2.5 0.0 2.0 4.0 6.0 8.0 10.0 Distribution of dC/dz / AU Capacitive coupling, dC/dz / AU

Unmodified Anionic Cationic

UK Patent Application No. 1607802.4; J.C. Courtenay, M.A. Johns, F. Galembeck, C. Deneke, E.M. Lanzoni, C.A. Costa, J.L. Scott, R.I. Sharma, Biomaterials, 2016, submitted

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Influence of degree of modification on dC/dz

0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 0.0 2.0 4.0 6.0 8.0 10.0

Capacitive coupling, dC/dz / AU Degree of Substitution / %

Low degrees of modification promote cell attachment; scaffolds have the materials properties associated with cellulose, yet allow attachment without mediating proteins

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More sophisticated scaffolds Not yet cleared for publication to be covered in lecture

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Cellulose based Formulation Ingredients: rheology modifiers and Pickering emulsions

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Nanofibrillar oxidized cellulose as a key formulation ingredient in greener personal care products

ca 20 % of 1° alcohol oxidised

• R. J. Crawford, K. J. Edler, S. Lindhoud, J. L. Scott, G. Unali, Green Chem., 2012, 14, 300-303
• R. J. Crawford, J. L. Scott, G. Unali, PCT patent WO2010076292, 2010
• xidize &

disperse formulate

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Partially C(6) oxidised cellulose

• +

+ + + + + + + + + + + + + + + + + + + + + ++ + + + + +

Not dissolved! Well-dispersed fibrils with surface charge; bacterial cellulose X sodium carboxymethylcellulose (SCMC) hybrid Surfactant interactions? thixotropic gels

ca 20 % of 1° alcohol oxidised

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Application in personal care products

Sprayable gels, including alcohol containing gels Creams / lotions

• il in water

emulsions

• R. J. Crawford, K. J. Edler, S. Lindhoud, J. L. Scott, G. Unali, Green Chem., 2012, 14, 300-303
• R. J. Crawford, J. L. Scott, G. Unali, PCT patent WO2010076292, 2010
• J. L. Scott, C. Smith, G. Unali, PCT patent application WO2012171725, 2012

Rheology modifier in reduced surfactant formulations

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Sprayable gels - effect of alcohols on structure

Gravimetric “gel content”

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Sprayable gels – effect of ethanol on structure

Best fit models to Ethanol SAXS data 10% 20% 30% 40% 50% 60% 70% 80% 90% Elliptical cylinder P P P P X X X X X Minor radius / Å 18(1) 17(1) 18(1) 19(1) major/minor ratio 3(1) 3(1) 3(1) 2(1) Lamellar structure X X X X P P P P P bilayer thickness / Å 33(1) 35(1) 35(1)

Formation of sheet- like structures as alcohol content increases

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Change in gel structure - methanol

Dispersed OC (0.8 g L-1), 40 mM SDS Dispersed OC (0.8 g L-1) Supercritical drying after solvent exchange to methanol

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Rheology modifier for API formulations

• Stable and tolerant of alcohols
• Shear thinning (easy to apply or spray)
• Non-allergenic, non-irritant
• Non sticky with a pleasant “soft” skin feel
• Any advantages in API delivery through the skin?

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2 4 6 8 200 400 600 800

Time (hr)

Cumulative ibuprofen permeated (mg/cm2)

Sainsbury's Gel Ibuleve Formulation B Formulation C Formulation D Formulation E

Market 1, HEC, 5% active Market 2, carbomer, 5% active A, oxcell, 1% active B, oxcell, 1% active C, oxcell, 1% active D, oxcell, 1% active

data points slightly displaced on the time axis

2 4 6 8 1000 2000 3000 4000 5000 Time (hr) Cumulative ibuprofen released (mg/cm2)

B A Sainsbury's Ibuleve

A, oxcell, 1% active B, oxcell, 1% active Market 1, HEC, 5% active Market 2, carbomer, 5% active

Silicone membrane in vitro Porcine skin in vitro

• D. Celebi, R.H. Guy, K.J. Edler, J.L. Scott,

Int, J Pharmaceutics, 2016, submitted

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Creams – particle stabilised O/W emulsions

Emulsion stabiliser in creams and lotions

• J. L. Scott, C. Smith, G. Unali, PCT patent application WO2012171725, 2012.
• Pickering emulsions
• Consistent droplet size
• Stable
• Pleasant tactile properties

tetradecane / water plus dispersed oxidised cellulose 0 g/L

• xidised cellulose

15 g/L

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Creams – particle stabilised O/W emulsions

freeze-dried hexane/water emulsion Pickering emulsions

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Oxidised cellulose – a versatile ingredient

• Simplified formulation “chassis” and reduced number of ingredients
• Good tactile properties – remarkable “skin feel” with no stickiness
• Versatile ingredient - sprayable lotions to spreadable creams
• Excellent emulsion stabilisation
• Maintains suspensions - no particulate settling
• Potential for use in mild skin treatment formulations

Limitations

• Tolerant of lower alcohols, but not glycerol
• Incompatible with cationic surfactants (cationic particles?)

… opportunity to use the same the principles to produce a cationic version

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Materials to Enable Electronics Recovery and Recycling

Closed Loop Emotionally Valuable E-waste Recovery

If the consumer is attached to the device’ appearance or feel They might be inclined to return it to the manufacturer for upgrade Allowing rapid exchange of superannuated hardware Upgraded device is immediately returned to the customer To recycling or material recovery

Skeleton: the support components inside the device Organs: the high-tech electronics that deliver the function Skin: the outer casing,

• r the part that the

user interacts with directly Skin

Complete disassembly required to allow recovery of components and/or metals

rejected components decompose, skeleton recover valuable parts recover valuable metals

valuable components & elements

???

Skeleton requirements

• Robust
• Rigid / flexible
• Non-conductive
• Non-flammable
• Smooth
• Printable
• Processible
• Degradable (triggered)

… CHEAP!

Cellulose processing

Dissolve in IL

Blend filler(s) Cast / form Set and leach Surface treat recover ionic liquid

Cellulose films – inorganic fillers

Cellulose film from 15 wt % solution in ionic liquid (cross section) Cellulose film with 15 % filler from 15 wt % solution in ionic liquid (cross section)

Cellulose films - fire retardant fillers

Cellulose film 50 wt% fire retardant filler Cellulose film with increasing quantities of nanoclay filler

5 wt % 10 wt % 20 wt %

Cellulose films – surface coated

Cellulose film Cellulose film + 10 wt % nanoclay Cellulose film coated with hydrophobising agent Cellulose film + 10 wt % nanoclay coated with hydrophobising agent

58 ° 97 ° 117° 48 °

ethyl-2-cyanoacrylate

Conductive ink printing

surface treated untreated

cellulose films no filler cellulose films with 20 % filler

Transparent, fire retardant, printable, biodegradable cellulose films

Details not yet cleared for publication to be covered in lecture

High filler content film particles too large – not transparent surface suitable for conductive printing reasonable flame retardancy degradation w cellulases Low filler content film transparent surface suitable for conductive printing good flame retardancy excellent degradation w cellulases

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Acknowledgements

University of Bath: Professor Karen Edler Dr Saskia Lindhoud Dr Duygu Celebi, Yun Jin Professor Richard Guy Dr Ram Sharma Jamie Courtenay, Marcus Johns Reggie Wirawan CLEVER: Dr Debra Lilley, Alan Manley and Dr Grace Smalley, Loughborough University Dr Ben Bridgens and Dr Keertika Balasundaram, Newcastle University Dr Kersty Hobson, Cardiff University Dr Nicholas Lynch, University of Oxford Dr Janet L. Scott, Dr Saravanan Chandrasekaran, Dr Alvaro Cruz-Izquierdo, University of Bath Industrial: Unilever, Croda, Rockwood Additives (FR&SH, oxcell) University of Campinas, Brazil: Professor Fernando Galembeck LNNano, Brazil: Dr Christoph Deneke Dr Evandro M. Lanzoni and Dr Carlos A. Costa University of East Anglia Professor Yaroslav Kimyak Dr Susana Campos E Menezes Jorge Ramalhete