Novel Mixing Device forPolyurethane Foam Scaffolds

Michael Scherer1, Dustin Dowell1, Andrew Solomon2, Scott Guelcher, Ph.D.,3

1Biomedical Engineering Department, 2Mechanical Engineering Department, 3Chemical Engineering Department Vanderbilt University School of Engineering, Nashville, Tennessee 37235

INTRODUCTIONINTRODUCTIONINTRODUCTIONINTRODUCTION

Polyisocyanates, when exposed to water, react to produce carbon dioxide. This reaction has recently been implemented in the synthesis of polyurethane (PUR) foams used for tissue scaffolding. Derived from an isocyanate and polyester triol combination, the resulting foam supports the attachment, proliferation, and differentiation of bone marrow stromal cells. Its porous structure allows these cells to propagate quickly through the scaffolding, accelerating the recovery process.

One current obstacle in the polymer's development is the creation of a novel mixing process for the polyol and isocyanate. Once mixed, the reaction begins immediately; the foam swells to more than 5 times its original volume within 10 minutes. As the window of operation for the foam is so small, it is essential that the new mixing system be simple and expedient while still producing a homogeneous product.

Our solution to this mixing issue requires the use of a small rotary driven turbine to evenly mix both elements in the operating room setting. Employing fluid mixing theory and mechanical design, we would develop a mixing device and test its feasibility in a laboratory setting.

Polyisocyanates, when exposed to water, react to produce carbon dioxide. This reaction has recently been implemented in the synthesis of polyurethane (PUR) foams used for tissue scaffolding. Derived from an isocyanate and polyester triol combination, the resulting foam supports the attachment, proliferation, and differentiation of bone marrow stromal cells. Its porous structure allows these cells to propagate quickly through the scaffolding, accelerating the recovery process.

One current obstacle in the polymer's development is the creation of a novel mixing process for the polyol and isocyanate. Once mixed, the reaction begins immediately; the foam swells to more than 5 times its original volume within 10 minutes. As the window of operation for the foam is so small, it is essential that the new mixing system be simple and expedient while still producing a homogeneous product.

Our solution to this mixing issue requires the use of a small rotary driven turbine to evenly mix both elements in the operating room setting. Employing fluid mixing theory and mechanical design, we would develop a mixing device and test its feasibility in a laboratory setting.

RESULTSRESULTSRESULTSRESULTS

MATERIALS AND METHODSMATERIALS AND METHODSMATERIALS AND METHODSMATERIALS AND METHODS

Components:

1. Hardener

a. Polyester (PCLG) triol

b. Water

c. TEGOAMIN 33 (catalyst)

d. Turkey red oil (stabilizer)

e. Calcium stearate (pore opener)

2. Isocyanate

a. DN3300A (HDI trimer)

Porous PUR scaffolds are synthesized

when the polyol and isocyanate react,

with CO2 acting as a blowing agent to

create pores.

Operating Room Procedure

1. Add hardener to isocyanate in sterile canister

2. Insert canister into fixture loading tray

3. Lower impeller into canister at preset mixing height

4. Mix for 40 seconds at level 2 mixing (11,000 RPM)

5. Turn off rotary device and withdraw the shaft from the canister

6. Remove canister from loading tray

7.Inject polyurethane

Components:

1. Hardener

a. Polyester (PCLG) triol

b. Water

c. TEGOAMIN 33 (catalyst)

d. Turkey red oil (stabilizer)

e. Calcium stearate (pore opener)

2. Isocyanate

a. DN3300A (HDI trimer)

Porous PUR scaffolds are synthesized

when the polyol and isocyanate react,

with CO2 acting as a blowing agent to

create pores.

Operating Room Procedure

1. Add hardener to isocyanate in sterile canister

2. Insert canister into fixture loading tray

3. Lower impeller into canister at preset mixing height

4. Mix for 40 seconds at level 2 mixing (11,000 RPM)

5. Turn off rotary device and withdraw the shaft from the canister

6. Remove canister from loading tray

7.Inject polyurethane

IMPELLER DESIGNIMPELLER DESIGNIMPELLER DESIGNIMPELLER DESIGN

Density and Porosity Characteristics

Young’s Modulus

Compressive Stress at 50% Deflection

Stress Relaxation

Density and Porosity Characteristics

Young’s Modulus

Compressive Stress at 50% Deflection

Stress Relaxation

PolyolComposition

Novel Mixing Device Results Accepted Values

Density (mg/cm3)

Porosity(vol %)

Density (mg/cm3)

Porosity(vol %)

1800/HDIt 134.34 88.90% 92.8 ±7.7 92.4 ±0.6

900/HDIt 97.53 91.97% 98.2 ±12.5 91.9 ±1.0

900+50PEG 84.00 93.10% 93.7 ±11.4 92.3 ±1.0

PolyolComposition

Novel Mixing Device Results Accepted Values

Young’s Modulus Young’s Modulus

1800/HDIt 42.62 ±13.6 25.5 ±1.5

900/HDIt 71.01 114.5 ±29.7

900+50PEG 6.61 14.6 ±2.7

0.00

50.00

100.00

150.00

200.00

250.00

300.00

350.00

0 5 10 15 20

Rel

axat

ion

Mo

du

lus

(KP

a)

Time (min)

900/HDIt (Novel Mixing)

900/HDIt (Coaxial Mixing)

Frequency Sweep

Frequency Sweep

RESULTS CONT’DRESULTS CONT’DRESULTS CONT’DRESULTS CONT’D

DISCUSSIONDISCUSSIONDISCUSSIONDISCUSSION

The primary goal of this project was to test a prototype axial mixer as a valid substitute for the current co-axial vortex method currently employed.

Our results indicate that:The rushton-turbine driven axial mixing is an effective, convenient, and cost-effective way to homogeneously mix PUR foams. The Young's Modulus for these foams are within an acceptable error range compared to accepted values. Both the 1800/HDIt and 900+50PEG are similar in stiffness, with the 900DHIt within an acceptable percentage deviation. The compressive stresses of the foams were very close to their accepted values, with no deviation greater than 17 Kpa.Novel mixing produced foams with nearly identical Storage and Loss Modulus.•Foams prepared with the stirred tank agitation method behave similarly over different compressive stress conditions.

 

The primary goal of this project was to test a prototype axial mixer as a valid substitute for the current co-axial vortex method currently employed.

Our results indicate that:The rushton-turbine driven axial mixing is an effective, convenient, and cost-effective way to homogeneously mix PUR foams. The Young's Modulus for these foams are within an acceptable error range compared to accepted values. Both the 1800/HDIt and 900+50PEG are similar in stiffness, with the 900DHIt within an acceptable percentage deviation. The compressive stresses of the foams were very close to their accepted values, with no deviation greater than 17 Kpa.Novel mixing produced foams with nearly identical Storage and Loss Modulus.•Foams prepared with the stirred tank agitation method behave similarly over different compressive stress conditions.

 

CONCLUSIONCONCLUSIONCONCLUSIONCONCLUSION

REFERENCESREFERENCESREFERENCESREFERENCES

The stirred tank agitation technique utilizing a Rushton turbine impeller provided adequate mixing as compared to the co-axial vortex method.  Radial mixing proved to be effective, producing foams with comparable densities and reflexive characteristics vital to the materials performance in practice. Moreover, the new process delivered comparable mixing in a more compact device with decreased cost.  Pending further evaluation, stirred tank agitation is a promising method for mixing PUR scaffolds in the operating room setting. 

The stirred tank agitation technique utilizing a Rushton turbine impeller provided adequate mixing as compared to the co-axial vortex method.  Radial mixing proved to be effective, producing foams with comparable densities and reflexive characteristics vital to the materials performance in practice. Moreover, the new process delivered comparable mixing in a more compact device with decreased cost.  Pending further evaluation, stirred tank agitation is a promising method for mixing PUR scaffolds in the operating room setting. 

Rushton Turbine designed to create an radial flow pattern

Outer Diameter: D0=.75”, Height: H=.25”

Container Diameter: Dc=1”

Radial Clearance Ratio: D0/D

c= .75

Minimal container bottom separation

Rushton Turbine designed to create an radial flow pattern

Outer Diameter: D0=.75”, Height: H=.25”

Container Diameter: Dc=1”

Radial Clearance Ratio: D0/D

c= .75

Minimal container bottom separation

Guelcher, Scott A., Abiraman Srinivasan, and Jerald E. Dumas. "Synthesis, Mechanical Properties, Biocompatibility, and Biodegradation of Polyurethane Networks From Lysine Polyisocyanates." Biomaterials 29 (2008): 1762-1775.

Guelcher, Scott A. "Biodegradable Polyurethanes: Synthesis and Applications in Regenerative Medicine." Tissue Engineering: Part B 14 (2008): 3-17. Guelcher, Scott, Abiraman Srinivasan, and Andrea Hafeman. "Synthesis, in Vitro Degradation, and

Mechanical Properties of Two-Component Poly(Ester-Urethane)Urea Scaffolds: Effects of Water and Polyol Composition." Tissue Engineering 13 (2007): 2321-2333. King, Paul H., and Richard C. Fries. Design of Biomedical Devices and Systems. New York: Marcel

Dekker, 2003. Oldshue, James Y. Fluid Mixing Technology. New York: McGraw Hill, 1983. Perry, R H., and D W. Green. Perry's Chemical Engineers' Handbook. 8th ed. New York: McGraw Hill, 2007. Tatterson, Gary B. Fluid Mixing and Gas Dispersion in Agitated Tanks. New York: McGraw Hill, 1991.

Polyol Composition

Novel Mixing Device Results Accepted Values

Compressive Stress (KPa) at 50% Deflection

Compressive Stress (KPa) at 50% Deflection

1800/HDIt 21.46 5.2 ±0.4

900/HDIt 14.06 10.5 ±1.0

900+50PEG17.66

6.7 ±0.6