Session 1 - Polyethylene - VALENCIA A, Sun 9:30 AM - 11:00 AM 0002 46th Annual Meeting, Orthopaedic Research Society, March 12-15, 2000, Orlando, Florida EFFECT OF STERILIZATION METHOD ON LONG-TERM STABILITY OF SHELF-STORED AND CLINICALLY- RETRIEVED UHMWPE +*Daniels, A U (A-*); *Charlebois, S J (A-*); **Johnson, R A (E-**); ***Haggard, W G (E-***); *Jahan, M S (A-****); *Buncick, M C (A-****) +*Univesity of Tennessee Campbell Clinic Department of Orthopaedic Surgery, Memphis, TN. 956 Court Ave Rm A302, Memphis, TN 38163, (901) 448-5880, Fax: (901) 448-6062, ddaniels@utmem.edu Introduction: There is evidence that slow chemical and microstructural changes in ultra-high molecular weight polyethylene (PE) over a period of years result in changes in mechanical properties--especially a loss of ductility [1] . In implanted PE joint replacement components, these changes may contribute to increased wear, and may increase the possibility of component fracture under cyclic loads. Previous reports suggest that the rate of change in PE with time is far more pronounced for PE sterilized by γ irradiation than for PE sterilized by ethylene oxide (EtO). In other words, γ sterilized PE has markedly less physico-chemical stability than EtO sterilized PE. This difference is generally attributed to reactive free radicals created by γ sterilization. The question addressed by this study was whether this difference in physico- chemical stability persists after years of shelf storage and/or implantation of PE joint replacement components. However, direct measurement of stability of a given specimen requires a novel analytical tool. Ordinary analytical methods deter- mine specimen chemistry or structure, but stability can only be inferred. For example, one can only guess whether a specimen with low free radical concentration and a high percentage of oxidized bonds is in a stable physico- chemical state or is continuing to change. IMC (isothermal microcalorimetry) is a rapid, sensitive, quantitative means to directly measure the overall physico-chemical stability of a material. For a given material and environment, the net rate of heat flow between a specimen and its surroundings at constant temperature is directly proportional to the net rate of all exothermic and endothermic processes taking place. IMC can measure the rates of small changes taking place slowly (e.g. ~1%/year) in a small specimen--e.g., ~1 g of polymer. For similar specimens and conditions, a higher heat flow rate indicates lower stability. IMC has been used to detemine stability of solid drug formulations [2], but not implant materials, prior to work begun by the authors [3,4]. Materials & Methods: Materials - PE specimens studied were total knee tibial plateau inserts (TPIs) provided by two implant manufacturers. The specimens had been either γ sterilized in air or EtO sterilized under industry-standard conditions and had been either archivally stored in air or retrieved from clinical patients in connection with revision surgery. Control specimens (simulated TPIs) were disks 1 cm thick x 7.6 cm diameter of a PE reference material (r.m. = HSS 4150 GUR). Number and types of specimens were as follows: Controls - 1 URM (unsterilized r.m., air-stored ~48 months) and 1 GRM (r.m. newly γ-sterilized in air). Actual TPIs - 3 ESS (EtO-sterilized, shelf-stored) , 5 GSS (γ-sterilized shelf-stored), and 5 GCR (γ-sterilized clinically-retrieved). Age of shelf-stored specimens ranged from 110-115 months for EtO-sterilized and 113-114 months for γ-sterilized. Clinically- retrieved γ-sterilized specimens had a wide variety of storage times (T1) before implantation and subsequent implantation times (T2). The T1+T2 combinations were 30+60, 69+30, 42+45, 75+17, 86+7 months plus, in all cases, ~12 months post-retrieval storage time. Therefore, the total time from sterilization to IMC evaluation was similar to that of shelf-stored specimens. For IMC evaluation, 3 mm diameter cylinders weighing 0.5g were obtained from each TPI or control, using a specially-designed punch. Methods - IMC determinations of stability were performed under simulated implant conditions as follows. Immediately after punching a PE specimen, it was sealed in a 20 ml glass ampoule with 10 ml of phosphate-buffered saline (7.4 pH). The ampoule was then inserted in one of the test wells of the IMC instrument (Model 4400, Calorimetry Science Corp.) previously stabilized at 37C. PE physico-chemical stability was defined as the mean heat flow rate (μ Watts) over the period from 15 to 20 hours after ampoule insertion into the test well. Results: Fig. 1 presents quantified results for all specimens. The findings were striking and unequivocal. EtO-sterilized PE, shelf-stored for 9+ years, showed the same stability as unsterilized PE shelf-stored for 4+ years. In contrast, stability of γ-sterilized PE was significantly less (p<0.01), both immediately after sterilization and for PE subject to 9+ years of either shelf storage alone or combined shelf- storage and implantation. Differences in heat flow rates suggest that γ-sterilized PE is 5 to 9X less stable than EtO sterilized PE. There was also no discernable differ- ence in stability between PE that was recently γ-sterilized (GRM) and PE that had been subjected to either 9+ of shelf-storage (all GSS specimens) or 9+ years of combined shelf storage and implantation (all GCR specimens). 0 2 4 6 8 10 12 14 16 18 20 GSS1 GSS2 GSS3 GSS4 GSS5 ESS1 ESS2 ESS3 URM GRM GCR1 GCR2 GCR3 GCR4 GCR5 UHMWPE samples Average heat flow rate 15-20 hrs ( μ W) mean ± s.d. Figure 1. IMC mean heat flow between 15 and 20 hours (± s.d.) for PE specimens in PBS at 37° C (n=3). Discussion: The TPIs and controls evaluated for stability using IMC were also evaluated by collaborating investigators for free radical concentration by ESR (electron spin resonance) and oxidation index by FTIR (Fourier transform infra- red) spectroscopy. Those results are being reported separately in detail. However, the ESR and FTIR data suggest reasons for the IMC results. As expected, no free radicals were detected in any of the EtO sterilized specimens, and this explains their higher stability. For γ-sterilized specimens, free radical concentrations were lower in most clinically-retrieved specimens than in shelf-stored. (This decrease may be attributable to increased free radical reaction rates at body vs. room temper- ature and under cyclic mechanical stress.) However, the γ-sterilized specimens with lower free radical concentrations did not exhibit improved stability (lower IMC heat flow rate). In seeking an explanation, it is worth noting that FTIR showed the clinically-retrieved specimens were substantially oxidized. It may be that the continued instability is due to a combination of free radical reactions and some type of hydrolytic degradation of the oxidized portions of the PE structure. In conclusion, the main findings of this IMC study of PE stability were that γ- sterilization of PE creates a much less stable structure than EtO sterilization, and that the difference in stability persists after many years of either shelf storage or clinical implantation, even when free radical concentration declines. To be more complete, the study should have included EtO-sterilized clinically-retrieved PE specimens (ECRs), but none were available. One ECR (T2 = 5 years) has now been obtained for study. References: [1] Trieu, et al., Orthop. Assoc. E.S.W. Abstracts 10:353 (1998). [2] Koenigbauer, et al., Pharma. Res. 9:939-944 (1992). [3] Daniels, et al., Trans. O.R.S. 23(1):101 (1998). [4] Daniels, et al., Trans. Soc. Biomaterials 21:348 (1998). Acknowledgements: Funding - NSF Industry-University Center for Biosurfaces, Wilhelm Endowment (U. Tenn., Memphis TN), Campbell Clinic, Inc., Memphis TN. PE specimens - Smith & Nephew Orthopaedics, Inc., Wright Medical Technology, Inc. **Smith & Nephew Orthopaedics, Inc, Memphis, TN. ***Wright Medical Technology, Inc, Arlington, TN. ****Department of Physics, Unversity of Memphis, Memphis, TN. View publication stats View publication stats