title: Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF-beta2) in the healing rabbit MCL.
abstract: We investigated biomechanical and collagen expression in a healing bilateral rabbit medial collateral ligament (MCL) model to human recombinant transforming growth factor beta (rhTGF-beta2) at three and six weeks. Each rabbit had rhTGF-beta2 in a bioabsorbable pellet administered in one side, with the contralateral side serving as control (no rhTGF-beta2). All MCL healed with rhTGF-beta2 producing a profoundly increased scar mass at three weeks which decreased in size toward control at six weeks. In-situ hybridization demonstrated collagen expression (type I and III) no different than control at three weeks, but by six weeks elevated expression of type I was seen. Biomechanical analysis at three weeks showed no effect of rhTGF-beta2 on structural properties. However, at six weeks rhTGF-beta2 significantly inhibited both the maximum load (p < 0.05) and energy absorbed (p < 0.05) with no change in stiffness. Despite increased type I collagen expression and profound increase in early scar mass, rhTGF-beta2 did not improve the structural properties. Whether the dose or mode of delivery is responsible for decline in structural properties cannot be determined in this design. We hypothesize investigations of healing ligaments to cytokines should have biologic and biomechanical properties correlated in the same study at a minimum of two time points.
authors.affiliation: Deportment of Orthopaedics and Rehabilitation, Vanderbilt Sports Medicine Center, Nashville, TN 37212, USA. kurt.spindler@mcmail.vanderbilt.edu
authors.forename: K P
authors.initials: KP
authors.lastname: Spindler
authors.forename: J M
authors.initials: JM
authors.lastname: Dawson
authors.forename: G C
authors.initials: GC
authors.lastname: Stahlman
authors.forename: J M
authors.initials: JM
authors.lastname: Davidson
authors.forename: L B
authors.initials: LB
authors.lastname: Nanney
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D004548:Elasticity / Q000187:drug effects; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D017403:In Situ Hybridization; D007718:Knee Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017888:Medial Collateral Ligament, Knee / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D016059:Range of Motion, Articular / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D053781:Transforming Growth Factor beta2; D016474:Weight-Bearing; D014945:Wound Healing / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; D011994:Recombinant Proteins; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2