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Nicotine delays tendon-to-bone healing in a rat shoulder model
L M Galatz1, M J Silva, S Y Rothermich
1Department of Orthopaedic Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8233, St. Louis, MO 63110, USA. galatzl@wustl.edu
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.
Clinical Relevance:
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.
Insights
Nicotine delays tendon-to-bone healing in rats by increasing inflammation and reducing cell proliferation. While mechanical properties eventually improve, they lag behind controls, highlighting a clinical concern for rotator cuff repair.
Area of Science:
- Orthopedic research
- Regenerative medicine
- Biomaterials science
Background:
- Nicotine's detrimental effects on bone healing are established.
- Its impact on tendon and ligament healing remains largely uninvestigated.
- This study addresses nicotine's effect on tendon-to-bone healing.
Purpose of the Study:
- To evaluate the impact of nicotine exposure on tendon-to-bone healing.
- To assess histological, cellular, and biomechanical changes following rotator cuff repair in a rat model.
- To determine the duration of nicotine's adverse effects.
Main Methods:
- Rotator cuff tendons in rats were transected and repaired.
- Nicotine or saline was administered via osmotic pumps for 10, 28, or 56 days.
- Histology, cell counting, PCNA immunohistochemistry, collagen type-I mRNA expression, and biomechanical testing were performed.
Main Results:
- Nicotine group exhibited prolonged inflammation and reduced cellular proliferation at early time points.
- Type-I collagen expression was lower in the nicotine group at 28 days.
- While mechanical properties improved over time, maximum stress and force were lower in the nicotine group at 10 and 28 days, respectively.
Conclusions:
- Nicotine significantly delays tendon-to-bone healing in a rat rotator cuff model.
- Chronic inflammation and decreased cell proliferation contribute to impaired healing.
- These findings suggest nicotine use is a critical clinical consideration for rotator cuff repair outcomes.
