The Novel Scavenging of Free Radicals in UHMWPE with TEMPO, a Nitroxide Antioxidant
1
Chumakov, M C; 2Silverman, J; +2Al-Sheikhly, M.
Fischell Department of Engineering, University of Maryland, College Park MD
+2 Department of Materials Science and Engineering, University of Maryland, College Park MD
[email protected]
1
Introduction: Ultra-high molecular weight polyethylene
(UHMWPE) has been the standard lining material used in total joint
arthroplasty for several decades. Yet, oxidative degradation can lead to
premature aging and wear of the material and implant, causing a painful
inflammation called peri-prosthetic osteolysis. The novel use of a
nitroxide antioxidant can prevent oxidation that causes wear of the
implant. Standard sterilization and crosslinking methods of gamma
radiation or high-energy electron beam produce alkyl free radicals in the
polymer chain. Alkyl radicals can react to form bimolecular crosslinks
at high dose rates, form long-lived allyl radicals, or react with oxygen at
low dose rates to form peroxyl radicals. These peroxyl radicals can
further interact with the polymer chain producing hydroperoxides and
more carbon-centered free radicals, leading to oxidative degradation. As
an alternative to post-irradiation annealing, which allows radical
recombination but reduces fatigue strength, antioxidants can be infused
into the UHMWPE to act as radical scavengers. Nitroxides are stable
organic compounds that have a strong paramagnetic signal and are very
efficient in preventing lipid peroxidation and providing radioprotection
in biological tissues[1, 2]. Nitroxides are also efficient carbon-centered
free radical scavengers[3]. Through the electron transfer mechanism,
radiolytically-produced carbon-centered free radicals in UHMWPE will
combine with the nitroxide radical.
Materials and Methods: The nitroxide used was 2,2,6,6–
Tetramethylpiperidine–1–oxyl (TEMPO). Ultra high molecular weight
polyethylene (UHMWPE) cylindrical disks were drilled into pellets of
1/8 in. diameter and 15 mm length (Biomet, Inc.,Warsaw, IN.) Some of
these pellets were then doped with TEMPO, and some were left as virgin
UHMWPE samples. Half the pellets were then packaged in Argon and
the rest irradiated in air. Two 60Co γ-ray sources and the 7 MeV electron
linear accelerator (LINAC), at the University of Maryland radiation
facilities, were used to irradiate and crosslink the UHMWPE polymer.
The dose rates used were 2.4 kGy h-1, 25 kGy h-1, and 650 kGy h-1.
Total irradiation doses consisted of 0 kGy, 30 kGy, and 100 kGy. After
irradiation, samples were transferred to quartz EPR tubes in an Argonfilled glove bag. A Bruker ESP 300 Electron Paramagnetic Resonance
(EPR) Spectrosmeter was used to detect the production of radiolyticallyproduced free radicals in UHMWPE, measure the consumption of the
TEMPO radical, and observe the interaction of nitroxide and UHMWPE
free radicals. EPR parameters were set to 2 mW power, 1 G modulation
amplitude, 163.84 ms time constant, and 100 kHz modulation frequency.
Results: TEMPO-doped UHMWPE exhibits a strong triplet structure
in the EPR. The TEMPO signature triplet was quantified using a
measure of the peak-to-peak heights. Naturally, the Argon packaged
samples exhibited lower free radical concentrations. The virgin
UHMWPE pellets demonstrated the characteristic allyl radical septet.
The alkyl radical is not visible due to the fast conversion to allyl during
the transfer time in the glove bag. As the TEMPO-doped UHMWPE
pellets were irradiated using 60Co γ-rays and electrons, the concentration
of TEMPO free radicals began to decrease.
Eventually, there is a nearly complete reduction in the TEMPO triplet
structure. Simultaneously, there in an increase in the allyl radical septet.
EPR Peak Heights with Irradiation Dose: TEMPO Triplet Central Peak in Doped UHMWPE and
Central Allyl Radical Peak.
Discussion: The TEMPO radical can oxidize to an oxoammonium
cation and reduce to a hydroxylamine. Yet, the TEMPO radical is the
only paramagnetic form and can thus be clearly distinguished from the
other species, as well as easily quantified. The reduction in free radical
concentration with irradiation dose, in the presence of TEMPO, while
the allyl radical concentration increases in virgin UHMWPE pellets,
indicates that the carbon-centered free radicals radiolytically produced in
UHMWPE are scavenged by the TEMPO radical. The reduction in
TEMPO radical concentration serves as an indicator that reaction (1) is
occurring. The TEMPO radical is indicated as >NO·, and >NOR is a
compound formed between the nitroxide and carbon-centered radical. It
can be postulated that reaction (2) will also occur in the presence of
oxygen. This may be molecular oxygen present in the amorphous
regions of UHMWPE or in the irradiation atmosphere.
R· + >NO· → >NOR
RO2· + >NO· ↔ intermediate → >N+=O + RO2-
(1)
(2)
This study did not take into account the effect of radical scavenging
on the crosslink density of the polymer. A complete reduction in alkyl
radicals would prevent crosslinking. Yet the use of the higher dose rate,
with the electron beam should provide immediate crosslinking, with
residual free radicals to react with TEMPO instead of oxygen. More
doses will also be used to fully investigate the kinetics of the above
reactions, with the use of EPR spectra.
References: [1] B. P. Soule, The chemistry and biology of nitroxide
compounds. Free Radical Biology & Medicine 42, 1632-1650 (2007).
[2] A. Samuni, S. Goldstein, A. Russo, J. B. Mitchell, M. C. Krishna and
P. Neta, Kinetics and Mechanism of Hydroxyl Radical and OH-Adduct
Radical Reactions with Nitroxides and with Their Hydroxylamines.
Journal of the American Chemical Society 124, 8719-8724 (2002).
[3] A. L. J. Beckwith, V. W. Bowry and K. U. Ingold, Kinetics of
nitroxide radical trapping. 1. Solvent effect. Journal of the American
Chemical Society 114, 4983-4992 (1992).
Acknowledgements: The authors are grateful for the kind donation
of UHMWPE extruded bar stock by Dr. David Schroeder (Biomet, Inc.,
Warsaw, IN.)
EPR Spectra of TEMPO-Doped UHMWPE Irradiated to 0 kGy, 30 kGy, and 100 kGy showing
consumption of nitroxide.
Poster No. 453 • 55th Annual Meeting of the Orthopaedic Research Society