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Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 1
Giyoong TaeJulia A. Kornfield
Chemical Engineering, California Institute of Technology
Jeffrey A. HubbellBiomedical Engineering, Swiss Federal Institute of Technology
Jyotsana LalIPNS, Argonne National Laboratory
Diethelm JohansmannMPI-Polymerforschung
Phase Behavior, Rheology, Erosion Kinetics and Biomedical Applications of
Fluoroalkyl-Ended PEGs
Motivation: In-Situ Transforming Hydrogels
Proteins or Cells
1) Delivery Carrier: Immobilization of cells or controlled release of proteins
2) Soft Structural Support orBarrier for Adhesion Prevention
solubilization
to
t1
t2
Applications Erosion typeSurface vs. Bulk
desired
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 2
Associative polymers
● With att racting groups
● Physical junctions : electrostatic hydrogen bonding hydrophobic
● Model system : End-group modified polymer in good solvent
Topo logy of Associative Network for “ Single Phase” Systems
superloops
superbridges
infinite clusters
C > CMC
C > C*
Increasing concentration(Annable, ‘93)
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 3
Phase Behavior of End-Associating Polymers
sol weak physical gel
single phase solution
Conc.
(stickiness)-1
two phases
Phase behavior governed by• attraction due to exchange entropy:
increases with aggregation number of core Nagg• repulsion due to excluded volume interaction:independent of chain length N
(Semenov, ‘95; Russel and coworkers, ‘98-’99)
Structure-Property Relations & Materials Design
● Phase behavior ● Rheology ● Erosion behavior ● Triggered solidification
● Midblock type & length● Hydrophobe type & length
● Midblock: PEG - why? biocompatible- length ∅ mesh size of gel
● Hydrophobe: fluoroalkyl, Rf
- why? hydrophobic and biocompatible- length ∅ strength of aggregation
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 4
Materials and Phase Behavior
type of equilibrium composition equilibrium compositionSample behavior in water (wt %) in PBS (wt %)
Cgel.eq. Csol.eq. Cgel.eq. Csol.eq.
20KC8 1 phase 20KC10 1 phase
10KC8 2 phase 6.5±0.2 0.075±0.005 7.8±0.2 0.055±0.00210KC10 2 phase 6.8±0.7 0.019±0.008 8.1±0.7 0.011±0.003
6KC6 2 phase 9.5±0.5 0.066±0.006 10.5±0.6 0.038±0.0026KC8 2 phase 11.0±0.3 0.042±0.007 12.5±0.3 0.017±0.001
6KC10 insoluble
Csol.eq.
Cgel.eq.
at 25 oC
H-C-N H
N-C-
=O
=O
Fluoroalkyl (Rf) :-(CH2)2-CnF2n+1
PEGIPDU (linker):
Dynamic moduli of “ single phase” species (20KC10)
101
102
103
104
105
G*
(Pa)
0.1 1 10 100 1000ωaT (rad/s) To = 25
oC
G' G"17 wt %12 wt %
5 wt %
25 oC 17 oC 9 oC 1 oC
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 5
103
104
105
Go (
Pa)
0.1 1 10 100
C (wt %)
3.0
2.5
2.0
1.5
1.0
0.5
τ (s)
302010
C (wt %)
Concentration dependence of Go and τ for “ single phase” species (20KC10)
2.1
Dynamic moduli of the equilibrium gels of species that show sol-gel coexistence
100
101
102
103
104
G' (
Pa)
0.01 0.1 1 10 100
ω (rad/s)
6KC810KC810KC10
100
101
102
103
104
G"
(Pa)
0.01 0.1 1 10 100
ω (rad/s)
6KC810KC810KC10
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 6
Nearly single relaxation behavior at Cgel,eq. (10KC10)
101
102
103
104
G*
(Pa)
0.01 0.1 1 10 100
ω (rad/s)
G'G"
1.0
0.5
0.010
-4x
G"
(Pa)
1.00.5
10-4
x G' (Pa)
Exp. Datasingle relaxation(m=0.5)m=0.49 with Gî=(GíGo-Gí2)m
Literature on Rheologyof Alkyl-ended “ Single Phase” Systems
η
C
log(η)
.log(γ)
G’
G”
log(ω)
log(G*)
C*
Go
η (or τ)
log(1/T)
G”
G’
τ
CC*1/τ
PEG
CnH2n+1
H2O
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 7
End-Dissociation Time and Apparent “ Effective Fraction” of Chains in the Gel
0.01
0.1
1
10
τ e.d
. (s)
1 10 100
CM1/2
(wt.fractn.)(g/mol)1/2
6KC8 10KC8 10KC10 20KC10
2.5
2.0
1.5
1.0
0.5
0.0
Go /
nkT
30252015105
C (wt %)
6KC8 10KC8 10KC10 20KC10
two phasesystemsshow Go > nkT
similar to other single phasesystems
}
}
Formation o f a new plateau at C > Cgel,eq.(10KC8)
C ♠ Cgel.eq.
} C > Cgel.eq.; new plateauat low freq.
1/τe.d.
end-group dissociation
Go: high freq. plateau
100
101
102
103
104
G*
(Pa)
0.1 1 10 100
ω (rad/s)
G' G"8 wt %
12 wt % 17 wt %
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 8
SANS (10KC8 at 25 oC)Aggregation number
Ordering Transition in the Gel Phase
0.01
0.1
1
I/φ (
cm-1
)
0.012 3 4 5 6 7 8 9
0.12
q (A-1
)
8 wt %12 wt %17 wt %
Species (wt %) Nagg
6KC8 (15) 32±4
10KC8 ( 8) 32±410KC8 (12) 32±4 10KC8 (17) 34±4
10KC10 (12) 50±6
20KC10 (12) 51±9
5KmC8 (0.5) 28 ±4
5KmC10 (0.5) 48 ±5
Implications for Theory
● Rheology of single-phase systems: » Annable’s could be improved by
better description of bridge:loop and inclusion of micelle-micelle repulsion
● Phase behavior:» Aggregation number is not the
primary determinant of the phase behavior as Semenov and Russelassume; deeper understanding of the effect of chain length on micelle-micelle repulsion is needed.
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 9
Polymer matrix erosion
Surface(heterogenous) vs. Bulk(homogeneous) erosion
desired for the controlled release
to
t1
t2
solubilization
Dissolution characteristics of polymer matrix by SPR in a flow system
Light
GlassMetalPolymerMatrix
Prism
water
θ
Reflected intensity
θθc θo
With increasing D or n
τ1 τ2 τ3
64
62
60
58Res
onan
ce A
ngle
(°)
403020100
Time (hr)
-dry-high n
-swollen-low n
-constant n∴ cons. c
10KC8 film (.55 µm, dried state)
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 10
Erosion Rates Correlate with Phase Behavior
phase composition dissolution rateSample behavior (wt %) (mg/cm2/hr)
5K-M-C10 lyotropic gel 12.8 0.201 20KC10 single phase 10.0 0.168
6KC8 sol-gel coex. 11.0 3.33 x 10-4
10KC8 sol-gel coex. 6.5 1.67 x 10-3
10KC10 sol-gel coex. 6.8 too slow to measureby SPR
Summary of Gel Properties in the Sol-Gel Coexistence Regime
● Mechanical properties (modulus, viscosity) can be controlled by the manipulation of hydrophilic and hydrophobic parts.
● Erosion of the matrix is achieved from the surface (heterogeneous type).
● Dissolution rates are much slower (~10-3 times) than systems with no phase separation.
● Dissolution is an activated process governed by end group length (10KC10 vs. 10KC8).
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 11
Sol-Gel Transition with Water-Miscible, Bio-Tolerable Organic Solvent
(N-methyl pyrrolidone (NMP))
Conc. solution in NMP (Injectible)
Gel
NMP diffusion-out& water absorption
Viscosity change at 37 oCafter exposing 50 % 10KC8 in NMPto water reservoir.
For initial thickness d ~ 1.5 mmtransition occurs within 10 min.
time (min)
1
10
100
1000
1 10 100 1000 10000
Initial Value
η *(ω
∅0)
(Pa
sec)
Human growth hormone (hGH)
● A single-chain polypeptide of 191 AAs with 2 disulfide bonds. M.W. ~ 22 KD
● Synthesized and secreted into storage granules as dimerwith 2 Zn2+ ions and then released from the anterior pituitary.
● Deficiency prevents normal growth, so the recombinant form (rhGH) is used to treat hGH deficient children.
● Current clinical administration : daily injections for several years => need for sustained release systems.
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 12
Release of hGH from In-Situ Forming Hydrogels of PEG with Fluorocarbon Ends
Protein precipitate
● The equilibrium gel phase of PEG modified with fluorocarbon ends shows slow, surface erosion.
● Injectible state by dissolving in NMP.
● Gelation after injection by diffusion of NMP out and water in.
● Sustained release of protein through the hydrogel.
Release experiment protocol for NMP formulation
• Dissolve PEG-Rf in NMP.
• Add protein powder (protein:PEG-Rf :NMP = 1:10:10).
• Inject the suspension into PBS
• Collect the supernatant at intervals and refill.
• Measure total protein concentration. Protein precipitate
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 13
hGH-Zn release from injectible NMP formulation 6KC8 at 37 oC to PBS buffer, thickness of gel at eq. ~ 0.25 cm
initial gel state of 1 :10:10 (weight) of hGH:Polymer:NMP
exchange of NMP for water
hGH standard
gel prepared by:1.0
0.8
0.6
0.4
0.2
0.0
Am
ount
Rel
ased
(%
)
3020100
t1/2 (hr1/2)
100x10-3
50
0
Abs
. at 2
20 n
m (
arb.
)
1614
t (min)
day2 : 6 : 9 :
Blood response to foreign materials
FOREIGN SURFACEFlowing blood
PROTEIN ADSORPTIONHigher flow rate; arterial
Lower flow rate; venous
PLATELET AGGREGATION(WHITE THROMBOSIS)
FIBRIN FORMATION+
PLATELET AGGREGATION+
TRAPPED RED CELLS(RED THROMBOSIS)
Ref.; Hoffman, A.S., Polymeric Materials and Artificial Organs, 1984, p.27
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 14
Rf-PEGs as surface-modifying materials for PTFE
• Rf-PEGs with long enough Rf showed slow (6KC8, 10KC8, 10KC10) or no (6KC10) erosion. → Adsorbed Rf-PEGs on PTFE can give a long-lasting surface-modifying coating.
• Suggests easy route to PEG surface layer on teflon:• 1.Immerse PTFE part in a solution of Rf-PEG in ethanol (1 wt %). • 2. Remove to leave a viscous liquid film on the surface, and • 3. immerse in water to induce association of the Rf groups with each
other and the PTFE surface.
• Observe that PTFE surface is hydrophilic after adsorption.
Capillarity of small PTFE tube
(a) Before Coating (Bare PTFE); Capillary Depression (Non-Wetting)
(b) After Coating; Capillary Rise (Wetting)
Direction of Tube Movementh
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 15
Change of capillary rise of modified PTFE tube with time under flow
(I.D =1.35 mm,varying shear rate (sec-1))
10KC10 6KC10
1 10 1000
4
8
12
16
20
Ca
pill
ary
ris
e (
mm
)
time (hr)
τw (Pa) 0.03 0.6 1.2
1 10 1000
4
8
12
16
20
Ca
pill
ary
ris
e (
mm
)
time (hr)
τw (Pa) 0.03 1.2 2.0
Results for PTFE modification
• Surface adsorption of Rf-PEGs onto PTFE effectively modifies the surface from being hydrophobic to hydrophilic.
• Capillary rise method is a sensitive tool to monitor the change in the surface properties of a narrow tube.
• Stability of this physisorption under flow correlates with the phase behavior and erosion rate of the bulk state of Rf-PEGs. In particular, an Rf-PEG that is insoluble in water provides the most stable modification.
Flow and Fracture of Transient Networks (ITP Complex Fluids Program 4/04/02)
Dr. Julia Kornfield, Caltech 16
Acknowledgment
● Thio E. Hogen-Esch (Synthesis) Chemistry, USC
● Diethelm Johannsmann (SPR characterization) MPI for Polymer Research, Germany
● Jyotsana Lal (SANS)Argonne National Lab, USA
● Ministry of Education, Korea Government