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

Centre for Sustainable Chemical Technologies Functional materials from cellulose: tissue scaffolds, formulation ingredients and printed materials Janet L. Scott ChemSpec June 2016, Basel

… or how to turn into

Centre for Sustainable Chemical Technologies 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.

Centre for Sustainable Chemical Technologies Cellulose based scaffolds for tissue engineering

Centre for Sustainable Chemical Technologies Cellulose as a tissue scaffold material? • Biocompatible • Foreign body reaction is relatively mild 1 • Oxidised cellulose is bioresorbable 2 • 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 non-specific protein adsorption; mammalian cells do not 1. T. Miyamoto, et al ., J. Biomed. Mat. Res., 1989, 23, 125-133 US 6500777, Bioresorbable oxidized cellulose composite …, Ethicon, 2002 readily attach to cellulose surfaces 2.

Centre for Sustainable Chemical Technologies Cellulose is readily functionalised Oxidation – negatively charged surface Substitution – positively charged surface

Centre for Sustainable Chemical Technologies Characterisation: conductometric titration and ss NMR [ppm] 1 H – 13 C CP MAS @ 10 kHz with a contact time of 2000 µs (300 MHz solid – state NMR)

Centre for Sustainable Chemical Technologies Cell attachment Cells attached to cationic cellulose 100 Cellulose films 90 Cellulose films + FBS Cell attachment / % Cellulose films + RGD 80 70 60 50 40 30 20 10 400 µm 0 Unmodified Cationic Anionic Cell attachment (%) = 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

Centre for Sustainable Chemical Technologies Cell spreading on scaffolds 1 Cationic cellulose = 1h 1h - Circularity 24 h - Circularity MG63 cell circularity 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 Blue = cell nucleus 1 = cell is circular,  0 = cell is spreading Green = cell membrane Blue = cell nucleus Green = cell membrane

Centre for Sustainable Chemical Technologies Cells attach and spread on cationised cellulose without intervention of proteins or ligands Cellulose scaffold bearing positive surface charge

Centre for Sustainable Chemical Technologies Bacterial cellulose films with modified surfaces 400 nm 400 nm 400 nm Surface topography inferred from tip amplitude measurements in electrostatic force microscopy (1 µm 2 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

Centre for Sustainable Chemical Technologies Capacitive coupling ( dC/dz ) Anionic Cationic Unmodified 2.5 Unmodified Distribution of dC/dz / Anionic 2.0 Cationic 1.5 AU 1.0 0.5 0.0 0.0 2.0 4.0 6.0 8.0 10.0 Capacitive coupling, dC/dz / AU 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

Centre for Sustainable Chemical Technologies Influence of degree of modification on dC/dz 7.0 Capacitive coupling, dC/dz 6.0 5.0 4.0 / AU 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

Centre for Sustainable Chemical Technologies More sophisticated scaffolds Not yet cleared for publication to be covered in lecture

Centre for Sustainable Chemical Technologies Cellulose based Formulation Ingredients: rheology modifiers and Pickering emulsions

Centre for Sustainable Chemical Technologies Nanofibrillar oxidized cellulose as a key formulation ingredient in greener personal care products ca 20 % of 1° alcohol oxidised oxidize & formulate disperse 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

Centre for Sustainable Chemical Technologies 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

Centre for Sustainable Chemical Technologies 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

Centre for Sustainable Chemical Technologies Sprayable gels - effect of alcohols on structure Gravimetric “gel content”

Centre for Sustainable Chemical Technologies Sprayable gels – effect of ethanol on structure Formation of sheet- like structures as alcohol content increases Best fit models to Ethanol SAXS data 10% 20% 30% 40% 50% 60% 70% 80% 90% P P P P Elliptical cylinder 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) P P P P P Lamellar structure X X X X bilayer thickness / Å 33(1) 35(1) 35(1)

Centre for Sustainable Chemical Technologies Change in gel structure - methanol Dispersed OC (0.8 g L -1 ), Supercritical drying after 40 m M SDS solvent exchange to methanol Dispersed OC (0.8 g L -1 )

Centre for Sustainable Chemical Technologies 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?

Centre for Sustainable Chemical Technologies 800 Porcine skin Market 1, HEC, 5% active Sainsbury's Gel Cumulative ibuprofen permeated ( m g/cm 2 ) Ibuleve Market 2, carbomer, 5% active in vitro Formulation B A, oxcell, 1% active 600 Formulation C B, oxcell, 1% active Formulation D C, oxcell, 1% active 400 Formulation E D, oxcell, 1% active 200 0 0 2 4 6 8 5000 A, oxcell, 1% active A Time (hr) B, oxcell, 1% active Cumulative ibuprofen B data points slightly displaced on the time axis 4000 released ( m g/cm 2 ) Market 1, HEC, 5% active Ibuleve Market 2, carbomer, 5% Sainsbury's 3000 active 2000 Silicone membrane 1000 in vitro 0 2 4 6 8 D. Celebi, R.H. Guy, K.J. Edler, J.L. Scott, Time (hr) Int, J Pharmaceutics , 2016, submitted

Centre for Sustainable Chemical Technologies Creams – particle stabilised O/W emulsions tetradecane / water plus dispersed oxidised cellulose 0 g/L oxidised cellulose 15 g/L • Pickering emulsions • Consistent droplet size • Stable Emulsion stabiliser in • Pleasant tactile properties creams and lotions J. L. Scott, C. Smith, G. Unali, PCT patent application WO2012171725, 2012.

Centre for Sustainable Chemical Technologies Creams – particle stabilised O/W emulsions Pickering emulsions freeze-dried hexane/water emulsion

Centre for Sustainable Chemical Technologies 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

Centre for Sustainable Chemical Technologies 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 To recycling or Allowing rapid material recovery exchange of superannuated hardware