Nicotine delays tendon-to-bone healing in a rat shoulder model.
BACKGROUND
Many studies have shown that nicotine negatively impacts fracture healing and bone fusion processes. However, very little is known about its effect on tendon and ligament healing. The goal of the present study was to evaluate the effect of nicotine on tendon-to-bone healing.


METHODS
Supraspinatus tendons in both shoulders of seventy-two rats were transected and repaired to the humeral head. Osmotic pumps were implanted subcutaneously, and nicotine or saline solution was delivered for ten, twenty-eight, or fifty-six days. Cell morphology was evaluated with use of histologic sections. Cells were counted, and proliferating cell nuclear antigen (PCNA) immunohistochemistry was performed to assess cellular proliferation. In situ hybridization was performed to measure type-I collagen mRNA expression. Biomechanical and geometric properties were assessed.


RESULTS
Inflammation persisted longer in the nicotine group than in the saline solution group. Cellular proliferation was higher in the saline solution group than in the nicotine group at the early time-points. Type-I collagen expression was higher in the saline solution group at twenty-eight days. Mechanical properties increased over time in both groups. Maximum stress was significantly lower in the nicotine group than in the saline solution group at ten days. Maximum force was significantly lower in the nicotine group than in the saline solution group at twenty-eight days. Maximum force was significantly higher in the nicotine group than in the saline solution group at fifty-six days. Stiffness was not different between the groups at any time-point.


CONCLUSIONS
Nicotine caused a delay in tendon-to-bone healing in a rat rotator cuff animal model. Mechanical properties increased over time in both groups, but the properties in the nicotine group lagged behind those in the saline solution group. Chronic inflammation and decreased cell proliferation may partly explain the inferior biomechanical properties in the nicotine group as compared with the saline solution group.


CONCLUSIONS
Failure of rotator cuff repair is a major clinical problem. The adverse effect of nicotine on rotator cuff healing noted in this clinically appropriate animal model may be an important clinical consideration.
Galatz
L M
LM
Department of Orthopaedic Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8233, St. Louis, MO 63110, USA. galatzl@wustl.edu
Silva
M J
MJ
Rothermich
S Y
SY
Zaegel
M A
MA
Havlioglu
N
N
Thomopoulos
S
S
D000818:Animals; D001696:Biomechanical Phenomena; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000070636:Rotator Cuff Injuries; D014945:Wound Healing / Q000187:drug effects*
D018722:Nicotinic Agonists; D018809:Proliferating Cell Nuclear Antigen; D009538:Nicotine