title: Exogenous collagen cross-linking recovers tendon functional integrity in an experimental model of partial tear.
abstract: We investigated the hypothesis that exogenous collagen cross-linking can augment intact regions of tendon to mitigate mechanical propagation of partial tears. We first screened the low toxicity collagen cross-linkers genipin, methylglyoxal and ultra-violet (UV) light for their ability to augment tendon stiffness and failure load in rat tail tendon fascicles (RTTF). We then investigated cross-linking effects in load bearing equine superficial digital flexor tendons (SDFT). Data indicated that all three cross-linking agents augmented RTTF mechanical properties but reduced native viscoelasticity. In contrast to effects observed in fascicles, methylglyoxal treatment of SDFT detrimentally affected tendon mechanical integrity, and in the case of UV did not alter tendon mechanics. As in the RTTF experiments, genipin cross-linking of SDFT resulted in increased stiffness, higher failure loads and reduced viscoelasticity. Based on this result we assessed the efficacy of genipin in arresting tendon tear propagation in cyclic loading to failure. Genipin cross-linking secondary to a mid-substance biopsy-punch significantly reduced tissue strains, increased elastic modulus and increased resistance to fatigue failure. We conclude that genipin cross-linking of injured tendons holds potential for arresting tendon tear progression, and that implications of the treatment on matrix remodeling in living tendons should now be investigated.
authors.affiliation: Department of Orthopedics, University Hospital Zurich, Balgrist, Forchstrasse 340, 8008 Zurich, Switzerland.
authors.forename: Gion
authors.initials: G
authors.lastname: Fessel
authors.forename: Jeremy
authors.initials: J
authors.lastname: Wernli
authors.forename: Yufei
authors.initials: Y
authors.lastname: Li
authors.forename: Christian
authors.initials: C
authors.lastname: Gerber
authors.forename: Jess G
authors.initials: JG
authors.lastname: Snedeker
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004548:Elasticity / Q000187:drug effects / Q000528:radiation effects; D006736:Horses; D039823:Iridoids / Q000378:metabolism / Q000494:pharmacology*; D022125:Lacerations / Q000378:metabolism / Q000628:therapy; D011765:Pyruvaldehyde / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D020127:Recovery of Function; D013708:Tendon Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013710:Tendons / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D014467:Ultraviolet Therapy; D014945:Wound Healing / Q000502:physiology
chemical_list: D003432:Cross-Linking Reagents; D039823:Iridoids; D011765:Pyruvaldehyde; D003094:Collagen; C007834:genipin