Nitrous acid pretreatment of tendon xenografts cross-linked with glutaraldehyde and sterilized with gamma irradiation

Collagenous xenografts made from kangaroo tail tendon cross-linked with glu taraldehyde have a potential application in the reconstruction of massive d igital tendon deficits. However, a limitation to the clinical use of these xenografts has been the optimization of collagen cross-linking, and subsequ ent bio-incorporation and retention of mechanical properties following impl antation. The purpose of this study was to evaluate the effect of nitrous a cid on modulating the biologic and mechanical properties of tendon xenograf ts cross-linked with glutaraldehyde. Tendon xenografts were pretreated with 0.1 or 0.01 M nitrous acid solution, prior to cross-linking in 2% glutaral dehyde and sterilization by gamma irradiation. Xenografts were implanted in tramuscularly in rabbits to examine biocompatability, and also used to repa ir ovine digital extensor tendon deficits to evaluate functional incorporat ion. Histologically, intramuscularly implanted nitrous acid pretreated xeno grafts in rabbits had a greater degree of diffuse cellular infiltration int o interstitial splits in the graft than controls after 12 weeks. Xenografts implanted in an ovine extensor tendon deficit were evaluated after 26 and 52 weeks. Rate of failure of tenorrhaphies between host tendon and xenograf ts overall (15/21) was significantly greater (P < 0.05) than for autografts (1/21), suggesting that the holding power of sutures in xenografts was inf erior to that obtained in autografts. Tensile failure stress of midsections of both nitrous acid pretreated and control xenografts was about 100 MPa p rior to implantation (time zero). After 26 and 52 weeks, failure stress of both types of xenografts was significantly less than at time zero (P < 0.05 ). At 52 weeks, failure stress of nitrous acid pretreated xenografts (47.4 +/- 3.1 MPa) was significantly less than control xenografts (63.7 +/- 5.4 M Pa); (P < 0.05). However, nitrous acid pretreated xenografts were similar t o control xenografts in failure load (357 +/- 29 and 354 +/- 26 N, respecti vely), but they tended to have larger cross-sectional areas (7.6 +/- 0.5 ve rsus 5.7 +/- 0.6 mm(2), respectively) which were responsible for the lower calculated value for failure stress. Histologically, autografts maintained their normal tissue architecture and evoked a more limited cellular respons e in surrounding tissues than xenografts (P < 0.05). Both types of xenograf t were surrounded by a thicker cuff of cellular response than autografts. H owever, compared to control xenografts, nitrous acid pretreated xenografts had more extensive fragmentation and splitting of collagen bundles, and mor e diffuse cellular and vascular infiltration into these interstitial splits , and these alterations were apparently contributing to the greater 'swelli ng' of these xenografts. It was concluded that pretreatment of tendon xenog rafts with nitrous acid modulated their biologic and material properties. F urther studies are needed to elucidate the mechanism of these effects, and to determine if the protocol for tendon xenograft preparation could be opti mized for improved clinical performance. (C) 1999 Elsevier Science Ltd. All rights reserved.