Download Functional materials from cellulose: tissue scaffolds, formulation

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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
of 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)
Challenge: cellulose is a hydrophilic material with low
adsorption;
mammalian cells do not
1.non-specific
T. Miyamoto, et al.,protein
J. Biomed. Mat.
Res., 1989, 23, 125-133
2. US 6500777, Bioresorbable
oxidized cellulose
composite …,surfaces
Ethicon, 2002
readily attach
to cellulose
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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
100
Cell attachment / %
90
80
Cells attached to cationic cellulose
Cellulose films
Cellulose films + FBS
Cellulose films + RGD
70
60
50
40
30
20
10
400 µm
0
Unmodified
Cell attachment (%) =
Cationic
Anionic
No. of cells on scaffold
× 100
Seeding density
Solution: surface modification (cationic) promotes cell
attachment without mediation by added proteins
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
MG63 cell circularity
1
1h - Circularity
24 h - Circularity
Cationic cellulose = 1h
0.8
0.6
0.4
0.2
Cationic cellulose = 24h
0
Control
Unmodified
0.6 DS
4.7 DS
9.2 DS
Scaffold
Circularity = 4π (Area)/ (Perimeter)2
Cell circularity factor = measure of spreading
1 = cell is circular, 0 = cell is spreading
Blue = cell nucleus
Green = cell membrane
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
400 nm
400 nm
400 nm
Surface topography inferred from tip amplitude measurements in
electrostatic force microscopy (1 µm2 sample)
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)
Anionic
Unmodified
2.5
Cationic
Distribution of dC/dz /
AU
Unmodified
Anionic
Cationic
2.0
1.5
1.0
0.5
0.0
0.0
2.0
4.0
6.0
Capacitive coupling, dC/dz / AU
8.0
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
10.0
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Influence of degree of modification on dC/dz
Capacitive coupling, dC/dz
/ AU
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
0.0
2.0
4.0
6.0
8.0
10.0
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
oxidize &
disperse
formulate
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
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Partially C(6) oxidised cellulose
ca 20 % of 1°
alcohol oxidised
+
+ -+
+
+ - - + + -+
+- - -+
+
+- + - +
+- + +
+
- + --+ -+
+
+
+- -+
-+
+
+ - +
Surfactant
interactions?
thixotropic
gels
Not dissolved! Well-dispersed fibrils with surface charge;
bacterial cellulose X sodium carboxymethylcellulose (SCMC) hybrid
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Application in personal care products
Rheology modifier in
reduced surfactant
formulations
Creams /
lotions
oil in water
emulsions
Sprayable gels, including
alcohol containing gels
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
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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
Formation of sheetlike structures as
alcohol content
increases
Best fit models to Ethanol SAXS data
10% 20% 30% 40% 50% 60% 70% 80% 90%
Elliptical cylinder
X
X
X
X
X
P
P
P
P
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)
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Change in gel structure - methanol
Dispersed OC (0.8 g L-1),
40 mM SDS
Supercritical drying after
solvent exchange to methanol
Dispersed OC (0.8 g L-1)
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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?
Porcine skin
in vitro
Cumulative ibuprofen
released (mg/cm2)
5000
Cumulative ibuprofen
permeated (mg/cm2)
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A,
A oxcell, 1% active
Sainsbury's
Market
1, HEC,Gel
5% active
Ibuleve
Market
2, carbomer, 5% active
B
A,Formulation
oxcell, 1% active
C
B,Formulation
oxcell, 1% active
D
C, Formulation
oxcell, 1% active
Formulation E
D, oxcell, 1% active
600
400
200
0
0
2
4
6
8
Time (hr)
data points slightly displaced on the time axis
B,
B oxcell, 1% active
4000
800
Ibuleve 1, HEC, 5% active
Market
Market
2, carbomer, 5%
Sainsbury's
active
3000
2000
1000
0
2
4
6
Time (hr)
8
Silicone membrane
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
tetradecane / water plus dispersed oxidised cellulose
0 g/L
•
•
•
•
oxidised cellulose
Pickering emulsions
Consistent droplet size
Stable
Pleasant tactile properties
15 g/L
Emulsion stabiliser in
creams and lotions
J. L. Scott, C. Smith, G. Unali, PCT patent application WO2012171725, 2012.
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Creams – particle stabilised O/W emulsions
Pickering emulsions
freeze-dried hexane/water emulsion
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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
Upgraded device is
immediately returned
to the customer
Allowing rapid
exchange of
superannuated
hardware
To recycling or
material recovery
Skeleton: the support components
inside the device
Skin
Skin: the outer casing,
or the part that the
user interacts with
directly
Organs: the high-tech electronics that deliver the function
Complete disassembly required to allow
recovery of components and/or metals
Skeleton requirements
• Robust
• Rigid / flexible
• Non-conductive
• Non-flammable
• Smooth
• Printable
• Processible
• Degradable (triggered)
… CHEAP!
rejected
components
recover
valuable
metals
valuable
components
& elements
recover
valuable
parts
???
decompose,
skeleton
Cellulose processing
Surface treat
recover ionic liquid
Set and leach
Cast / form
Blend filler(s)
Dissolve in IL
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
117°
48 °
Cellulose film
Cellulose film
coated with hydrophobising agent
ethyl-2-cyanoacrylate
58 °
Cellulose film + 10 wt % nanoclay
97 °
Cellulose film + 10 wt % nanoclay
coated with hydrophobising agent
Conductive ink printing
cellulose films
no filler
untreated
surface treated
cellulose films
with 20 % filler
Transparent, fire retardant, printable,
biodegradable cellulose films
High filler content film
Low filler content film
particles too large – not transparent
transparent
surface suitable for conductive printing surface suitable for conductive printing
reasonable flame retardancy
good flame retardancy
degradation w cellulases
excellent degradation w cellulases
Details not yet cleared for publication
to be covered in lecture
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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
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
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)