Each year, approximately 200,000 anterior cruciate ligament (ACL) ruptures occur among patients in the United States. In general, two graft options—autograft and allograft—are available for ACL reconstruction, with much debate regarding the functional outcomes of each graft type.
Graft failure rates are a major concern, with higher failure rates reported for allograft tissue compared to autograft in younger and high-demand athletic patient populations. The Multicenter Orthopaedic Outcomes Network (MOON) consortium has shed some light on this topic by demonstrating that allograft failure rates decrease as patient age increases. This finding is significant because it suggests that using allograft tissue in patients older than 25 years of age may be an acceptable alternative to autograft, with similar outcomes and failure rates but without the morbidity related to graft harvesting.
Allograft tissue use comes with its own unique set of risks, which range from host rejection to infection and possible disease transmission. The allograft tissue must be free of infectious viruses or bacterium and must meet an appropriate level of sterility to be ready for implantation. To ensure that grafts are free of infectious viruses, such as HIV and hepatitis, extensive donor medical history and comprehensive nucleic acid testing are required. In addition, the graft must be obtained in a sterile fashion and maintained to a sterility assurance level (SAL) of 10-6 organisms to help prevent infection in the recipient.
Once obtained, the allograft tissue undergoes continued processing to further increase the level of sterility. One method involves exposing the allograft to gamma irradiation. The irradiation process uses high-frequency electromagnetic radiation to disrupt the DNA (nucleic acids) of organisms to sterilize the tissue. Both the level of gamma irradiation and the specific temperature at which the irradiation is performed are important considerations.
Broad levels of gamma irradiation have been reported as a successful method for reducing the bioburden present on graft tissue. Several studies have demonstrated that up to 2.5 mrad are required to reduce bacterial counts and fungal spores and up to 5.0 mrad are required to eradicate viruses. According to a study by Mark A. Moore, PhD, a minimal amount of 1.29 mrad of gamma irradiation was needed to reduce viral amounts by 2 to 5 log on the soft tissue and bone allograft tested, thus helping to approach an SAL of 10-6 organisms.
Stability and safety
The vital question yet to be answered by the orthopaedic community is this: What is the safest level of gamma irradiation that can decrease graft contamination while maintaining optimal biomechanical integrity to improve outcomes and minimize failure rates?
Studies have found that exposure to 2.18 mrad of gamma irradiation at dry ice temperature (-109.3° F) did not appear to have deleterious effects on the tensile strength or modulus of elasticity of allograft tissue. It has also been reported that, compared to autograft tissue, allografts exposed to 1.3 mrad of gamma irradiation did not appear to have a significant difference in laxity as measured by the KT-1000 knee flexion test.
Other investigations, however, reached different conclusions. Four prospective randomized trials performed by Sun et al indicated that allografts exposed to 2.5 mrad of gamma irradiation had the following characteristics:
- a significantly greater failure rate than both autografts and non-irradiated allografts (34 percent versus 6.4 percent and 8.8 percent, respectively)
- increased clinical laxity compared to both autografts and non-irradiated allografts
- no significant differences among the three groups with regard to range of motion or International Knee Documentation Committee (IKDC) outcome scores
Studies also suggest that irradiation of hamstring allograft tissue compromised its biomechanical properties, resulting in clinically increased anterior translation and rotational instability. Additional studies by Rihn et al found similar outcomes. In comparing autograft to irradiated allograft, a significant difference in objective laxity was demonstrated as measured by the KT-1000 test and a physical exam. However, the rate of return to sports and IKDC outcome scores did not differ significantly. Rappe et al reported a 33 percent failure rate in patients who underwent ACL reconstruction using an Achilles tendon allograft that had been irradiated with 2.5 mrad of gamma irradiation. Among ACL reconstruction patients with non-irradiated Achilles tendon allografts, the failure rate was just 2.4 percent.
Unfortunately, many of these studies do not report the temperature at which the allograft was irradiated, which may have a clinically relevant effect on the biomechanical properties. Compared to irradiation at room temperature, gamma irradiation at dry ice temperature has been reported to cause less damage to the graft tissue. This is attributed to the reduction and diffusion of free radicals that can cause structural damage to the grafts.
Based on these findings, it appears that allografts irradiated with less than 2.2 mrad of gamma irradiation will provide maximal benefits of sterility without significantly affecting the graft's biomechanical properties, failure rates, clinical laxity, and functional outcome scores. Orthopaedic surgeons should be cautious about using allografts for ACL reconstruction that have been treated with more than 2.5 mrad of gamma irradiation.
Jesse Dashe, MD, and Robert L. Parisien, MD, are orthopaedic surgery residents at Boston University Medical Center; Emily J. Curry, BA, is a research coordinator at Boston University Medical Center; Asheesh Bedi, MD, is chief of sports medicine and team physician at the University of Michigan in Ann Arbor, Mich.; Xinning Li, MD, is assistant professor at Boston University School of Medicine (sports medicine and shoulder surgery) and team physician at Boston University.
- Allograft failure rates in ACL reconstruction decrease with increasing patient age. The use of allograft tissue in patients older than 25 years of age may be an acceptable alternative to autograft.
- Allografts must be obtained in a sterile fashion and maintained to an SAL of 10-6 organisms to help prevent infection.
- Exposure to gamma irradiation can successfully reduce the bioburden present on graft tissue.
- The temperature at which the allograft is irradiated may have a clinically relevant effect on its biomechanical properties.
- Gamma irradiation (less than 2.2 mrad) at dry ice temperatures may provide maximal benefits of sterility without significantly affecting the graft's biomechanical properties, failure rates, clinical laxity, and functional outcome scores.
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