Stabilization of irradiated allografts via crosslinking and free radical scavenging

Currently, the risk of disease transmission from allografts has been reduced through a system of screening methods organized by tissue banks. Terminal sterilization is possible with the use of ionizing irradiation, which has shown high efficiency for neutralizing pathogens. Unfortunately, irradiation is known to cause chain scission and crosslink degradation in collagen, leading to weakened mechanical properties and increased susceptibility to enzymatic digestion. Two methods of stabilizing allografts against the effects of irradiation were studied in this research. These methods included crosslinking via EDC or glucose, and free radical scavenging using mannitol, ascorbate, or riboflavin. The overall objective of this study was to assess the protective ability of each treatment in the presence of increasing irradiation dose based on mechanical properties and enzyme digestion. These studies also investigated the influence of tendon water content, and combination of crosslink and scavenging methods after exposure to irradiation. Our hypothesis was that crosslinking and free radical scavenging would aid in maintaining mechanical integrity and enzymatic resistance after gamma or ebeam irradiation. In general, crosslinking and free radical scavenging improved the mechanical properties and collagenase resistance of irradiated tendons. Glucose crosslinked tendons irradiated at 25 kGy were comparable in terms of strength to native tendon. Similarly, at 50 kGy EDC crosslinked tendons were comparable to untreated tendons irradiated at 25 kGy. Ascorbate and riboflavin were successful at protecting mechanical properties especially at 25 kGy. Most noteworthy were the combined treatments irradiated at 50 kGy, which matched native tendons mechanically and were highly resistive to collagenase. These treatments were unable to completely maintain properties at 50 kGy, which is closer to a clinically useful dose. The majority of treatments displayed improvements at 25 kGy. If allografts could be successfully stabilized from damage, ionizing irradiation could ensure not only disease free tissues, but also faster availability.M.S.Includes bibliographical references (p. 80-85)