Using Polycaprolactone

for Tissue Regeneration

A Research Study by: Satish Bhat

UCONN - STORRS

Biomedical engineering and tissue regeneration are novel fields of research. Lives are lost everyday across the world because of the lack of donor organs. By producing these organs artificially, those people would be able to continue their lives. It was hypothesized that polycaprolactone would be a viable material to use in tissue engineering. This hypothesis was based on previous research that had been done. In this study, many specific analytical tests had to be done to find valid results. For example, a NMR (Nuclear Magnetic Resonance) test was done as well as thermal analysis. During the course of the study, several important results were gained. Thus far, polycaprolactone has been shown as a valid material to be used in tissue engineering. The results of the NMR test showed the presence of stable ions in the polymer as polylactic acid. Polylactic acid is a polymer that is currently being successfully used in tissue engineering. Also, thermal analysis tests showed that the polymer is a thermoplastic and has very similar characteristics to polylactic acid. Results obtained suggest that polycaprolactone is a strong contender for tissue scaffolding. NMR results show the magnetic pulse for polycaprolactone was radiated back out at the same frequency as polylactic acid. Polylactic acid is successfully being used, and because polycaprolactone has similar characteristics; it can possibly be used in scaffolding. Lives can be saved with this research, and polycaprolactone also is better for the environment because of its biodegradability characteristics.

Abstract

Motivation

• Polycaprolactone is a seven-membered polymer with the formula (CH2)5CO2

• Lives are lost because organs die due to old age and disease – donor organs save those people

• Donors are not always available, synthetic organs come into play

Example of Tissue Scaffold

Hypothesis

• It has been hypothesized that polycaprolactone will have similar characteristics to polylactic acid, and will be a viable material for scaffolding

• Prior research has shown that PCL scaffolds “possess mechanical properties within the lower range of…bone, suggesting that they may have the ability to withstand early functional loading.”

How to create grafts for human use

Research Question

• Can polycaprolactone be used in tissue engineering?

• Being investigated by comparing to already used polymer, polylactic acid

• IF similar characteristics, then strong contender for use in scaffolding.

How to create polycaprolactone

Materials

• 0.0620g of Schwartz catalyst (Cp2ZrClH) at room temperature

• 0.0161g of initiator (terepthaldehyde) at room temperature

• 3mL of solvent (toluene) at room temperature

• Argon gas to replace atmosphere• Access to a clock• Liquid nitrogen• 1.0300g of caprolactone at room temperature• NMR test • GPC test• DSC test• Thermal analysis • Mechanical analysis • Stress test• Lab notebook• Ring• Test tube• Hot plate that can spin test tubes• Thermometer• Two 5mL syringes• Analytical balance• DSC pans

Chemical Structure of Caprolactone

Procedure

Add catalyst and initiator Add solvent Replace atmosphere

with argon gas

Heat, spin and freeze test tubeInject caprolactone

Run NMR, GPC, DSC, thermal, and

mechanical analysis

Record Results and analyze

Calculations

Monomer Initiator Catalyst Solvent Temperature

Description Caprolactone terephthaldehyde Cp2ZrClH toluene RT

Ratio 75 1 2 - -

Molecular Weight 114.14 134.13 257.8 - -

Density(g/ml) 1.030 - - - -

Moles 9.024E-03 1.203E-04 2.406E-04 - -

Mass(g) 1.030 0.016 0.060 - -

Volume(ml) 1.000 - - 3.000ml -

This figure shows the calculations used to obtain the amount of each substance.

This figure is the results of the NMR (Nuclear Magnetic Resonance) Test

NMR Results

Structures of Materials

CH2 O C

O

CH2 CH2 CH2 CH2 CH2 OH

a3 b3 c3 d3 e3fh

n

HClCp2ZrO

Og

a1

e1

b1c1

d1

O

O

a

b

c d

e

Polycaprolactone

Caprolactone/Zr = 1/2

Caprolactone

Cp2ZrHCl (Schwartz Reagent)

0 5 10 15 20

Elution Time (Min)

GPC Results

Mechanical Testing Results

0

2,000

4,000

6,000

8,000

10,000

0 5 10 15 20 25Strain

Str

ess,

MP

a

0

1,000

2,000

3,000

0.15 0.16 0.17 0.18 0.19 0.2 0.21 0.22Strain

Stre

ss, M

Pa

modulus

PCL Mn = 218,000

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

0 100,000 200,000 300,000 400,000

0

2

4

6

8

50

75

100

125

150

175

200

Mo

du

lus

, MP

a

Mn

Modulus Elongation

Elo

ng

ati

on

, %

DSC ResultsH

ea

t F

low

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

Hea

t Flo

w (

W/g

)

-80 -60 -40 -20 0 20 40 60 80

Temperature (°C)Exo Down Universal V4.2E TA Instruments

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

Hea

t Flo

w (

W/g

)

-80 -60 -40 -20 0 20 40 60 80

Temperature (°C)Exo Down Universal V4.2E TA Instruments

PCL

P(DL)LA

PCL-b-P(DL)LA

PCL-co-P(DL)LA

PCL

P(DL)LA

PCL-b-P(DL)LA

PCL-co-P(DL)LA

Heating Scan Cooling Scan

Temperature (C) Temperature (C)

Conclusions

• NMR Results show that peaks (hydrogen bonds) are in the same location as polylactic acid

• Peaks at 6.8, 4.0, 1.8, 0.5, 0.6, and 0.0 (same locations as polylactic acid)

• Possibly strong contender for tissue scaffolding

Polycaprolactone

Error Analysis

• Further research includes finding more materials that can be used in tissue engineering

• Argon gas was not injected perfectly due to the ring on the test tube not being tight enough

• All measurements are never perfect

Front light mount from PCL

Acknowledgements

Research was assisted by Assistant Professor at UCONN –

Storrs Dr. Alexandru Asandei and Graduate Student Christopher

Simpson.

Research was conducted at the Institute of Material Sciences –

Polymer Building, 97 North Eagleville Road, Storrs, CT.

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