.Methods
This project was approved by the University of Ottawa
Animal Care Committee. Rat knee contractures of various
severities were produced by extra-articular fixation
of one knee of 250 adult male Sprague–Dawley rats,
each weighing 325 g, aiming for a final sample size of 40
each for six durations: 1, 2, 4, 8, 16 or 32 weeks [7].
Briefly, under general anesthesia and alternating right
and left legs, a Delrin® plate was surgically fixed with
screws to the proximal femur and distal tibia. This surgical
internal fixation spanned the knee joint, away from
all intra-articular knee structures while achieving rigid
fixation in 45° of flexion [7]. Preoperatively the rats received
slow-release buprenorphine and ketamine. Bupivacaine
hydrochloride was applied transdermally at closure.
Rats had access to food ad libitum and their activity was
unrestricted in cages. Leg pain beyond 4 days post-op was
treated with gabapentin s/c for 7 days. Nonsteroidal antiinflammatory
medications were avoided. Wound infections
were treated with amoxicillin trihydrate/clavulanate
potassium orally twice daily for 7 days; fluoroquinolones
were avoided. More animals were operated in experimental
groups of greater severity in anticipation of attrition