functional materials from cellulose: tissue scaffolds ... · transparent, fire retardant,...

Centre for Sustainable Chemical Technologies

Functional materials from cellulose: tissue scaffolds, formulation ingredients and printed materialsJanet L. ScottChemSpec June 2016, Basel

… or how to turn

into


1. delicate cellulose hydrogel based scaffolds for tissue engineering;

2. particulate rheology modifiers and emulsion stabilisers that are effective at low weight percent inclusion in aqueous (and other) formulations; and

3. robust, flame retardant composites in a range of formats from beads to sheets.


Cellulose based scaffolds for tissue engineering


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, 125-1332. 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


Cellulose is readily functionalised

Oxidation – negatively charged surface

Substitution – positively charged surface


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)


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

0

10

20

30

40

50

60

70

80

90

100

Unmodified Cationic Anionic

Cel

l atta

chm

ent

/ %

Cellulose filmsCellulose films + FBSCellulose 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


Cell spreading on scaffolds

Cationic cellulose = 24h

Blue = cell nucleusGreen = cell membrane

Cationic cellulose = 1h

Circularity = 4π (Area)/ (Perimeter)2

0

0.2

0.4

0.6

0.8

1

Control Unmodified 0.6 DS 4.7 DS 9.2 DS

MG

63 c

ell c

ircul

arity

Scaffold

1h - Circularity 24 h - Circularity

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

Blue = cell nucleusGreen = cell membrane


Cells attach and spread on cationisedcellulose without intervention of proteins or ligands

Cellulose scaffold bearing positive surface charge


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



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

Dis

tribu

tion

of d

C/d

z/

AU

Capacitive coupling, dC/dz / AU

UnmodifiedAnionicCationic



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 10.0Cap

aciti

ve c

oupl

ing,

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


More sophisticated scaffolds

Not yet cleared for publication to be covered in lecture


Cellulose based Formulation Ingredients: rheology modifiers

and Pickering emulsions


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, 300-303R. J. Crawford, J. L. Scott, G. Unali, PCT patent WO2010076292, 2010

oxidize &disperse

formulate

http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&docid=7Zrje6H_18J53M&tbnid=Hp0XxRfQRrNZOM:&ved=0CAUQjRw&url=http://eaststuff.co.uk/collection-shampoo-30ml/&ei=wW1dU539GoWsOMTZgNAD&bvm=bv.65397613,d.ZWU&psig=AFQjCNFHF8Tx5FAymao7iTrNzbRc5KUbVQ&ust=1398718266833970

http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&docid=7Zrje6H_18J53M&tbnid=Hp0XxRfQRrNZOM:&ved=0CAUQjRw&url=http://eaststuff.co.uk/collection-shampoo-30ml/&ei=wW1dU539GoWsOMTZgNAD&bvm=bv.65397613,d.ZWU&psig=AFQjCNFHF8Tx5FAymao7iTrNzbRc5KUbVQ&ust=1398718266833970


Partially C(6) oxidised cellulose

---

-- --

-- -

-- -

-

-

--

--

-

-

-

-

-

-

-

--

-

-

-

++

+

+

++

++

+

+

+++

+

++

++

++++

++

+++

++

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

Surfactantinteractions?

thixotropicgels

ca 20 % of 1°alcohol oxidised


Application in personal care products

Sprayable gels, including alcohol containing gels

Creams / lotions

oil in water emulsions

R. J. Crawford, K. J. Edler, S. Lindhoud, J. L. Scott, G. Unali, Green Chem., 2012, 14, 300-303R. 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


Sprayable gels - effect of alcohols on structure

Gravimetric “gel content”


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


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


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?


0 2 4 6 80

200

400

600

800

Time (hr)C

um

ula

tive

ib

up

rofe

n

perm

eate

d (

mg

/cm

2) Sainsbury's Gel

IbuleveFormulation BFormulation CFormulation DFormulation 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 80

1000

2000

3000

4000

5000

Time (hr)

Cu

mu

lati

ve ib

up

rofe

n

rele

as

ed

(m

g/c

m2)

B

A

Sainsbury's

Ibuleve

A, oxcell, 1% active

B, oxcell, 1% active

Market 1, HEC, 5% active

Market 2, carbomer, 5% active

Silicone membranein vitro

Porcine skinin vitro

D. Celebi, R.H. Guy, K.J. Edler, J.L. Scott, Int, J Pharmaceutics, 2016, submitted


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 oxidised cellulose 15 g/L


Creams – particle stabilised O/W emulsions

freeze-dried hexane/water emulsion

Pickering emulsions


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


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

http://4.bp.blogspot.com/-hgFNVZlem_c/UY0vPdiAwTI/AAAAAAAABGM/rBO1zW-t7EI/s1600/componentes.jpg

http://4.bp.blogspot.com/-hgFNVZlem_c/UY0vPdiAwTI/AAAAAAAABGM/rBO1zW-t7EI/s1600/componentes.jpg

http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&docid=-reYjdN9yFl4HM&tbnid=6SFPsVJzTFi5uM:&ved=0CAUQjRw&url=http://infographicworld.com/exploded-cellphone-wired/&ei=A2N2U8KtGYiW0AXA6oHICg&v6u=https://s-v6exp1-ds.metric.gstatic.com/gen_204?ip%3D138.38.192.218%26ts%3D1400267323503687%26auth%3D3dxgppiuzlhr2lpmpmifs4hidwlee3ut%26rndm%3D0.025872132203278386&v6s=2&v6t=14382&bvm=bv.66699033,d.ZWU&psig=AFQjCNFR_f061XgWq2nulWXX2eEQSYzLOg&ust=1400353723584350

http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&docid=-reYjdN9yFl4HM&tbnid=6SFPsVJzTFi5uM:&ved=0CAUQjRw&url=http://infographicworld.com/exploded-cellphone-wired/&ei=A2N2U8KtGYiW0AXA6oHICg&v6u=https://s-v6exp1-ds.metric.gstatic.com/gen_204?ip%3D138.38.192.218%26ts%3D1400267323503687%26auth%3D3dxgppiuzlhr2lpmpmifs4hidwlee3ut%26rndm%3D0.025872132203278386&v6s=2&v6t=14382&bvm=bv.66699033,d.ZWU&psig=AFQjCNFR_f061XgWq2nulWXX2eEQSYzLOg&ust=1400353723584350

Skeleton: the support components inside the device

Organs: the high-tech electronics that deliver the function

Skin: the outer casing, or the part that the user interacts with directlySkin

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 % solutionin ionic liquid (cross section)

Cellulose film with 15 % filler from 15 wt % solution in ionic

liquid (cross section)

Cellulose films - fire retardant fillersCellulose 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 % nanoclaycoated with hydrophobising agent

58 ° 97 °

117°48 °

ethyl-2-cyanoacrylate

Conductive ink printing

surface treateduntreated

cellulose filmsno filler

cellulose filmswith 20 % filler

Transparent, fire retardant, printable, biodegradable cellulose films

Details not yet cleared for publication to be covered in lecture

High filler content filmparticles too large – not transparent

surface suitable for conductive printingreasonable flame retardancy

degradation w cellulases

Low filler content filmtransparent

surface suitable for conductive printinggood flame retardancy

excellent degradation w cellulases


AcknowledgementsUniversity of Bath:Professor Karen EdlerDr Saskia LindhoudDr Duygu Celebi, Yun JinProfessor Richard GuyDr Ram SharmaJamie Courtenay, Marcus JohnsReggie WirawanCLEVER:Dr Debra Lilley, Alan Manley and Dr Grace Smalley, Loughborough UniversityDr Ben Bridgens and Dr Keertika Balasundaram, Newcastle UniversityDr Kersty Hobson, Cardiff UniversityDr Nicholas Lynch, University of OxfordDr Janet L. Scott, Dr Saravanan Chandrasekaran, Dr Alvaro Cruz-Izquierdo, University of BathIndustrial: Unilever, Croda, Rockwood Additives (FR&SH, oxcell)

University of Campinas, Brazil:Professor Fernando GalembeckLNNano, Brazil:Dr Christoph DenekeDr Evandro M. Lanzoni and Dr Carlos A. CostaUniversity of East AngliaProfessor Yaroslav KimyakDr Susana Campos E Menezes Jorge Ramalhete

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