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Effect of hemorrhage on medial collateral ligament healing in a mouse model
Rick W Wright1, Manish Parikh, Tracy Allen
1Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, St Louis, Missouri 63110, USA.
Background:
Medial collateral ligament injuries heal by a scar response.
Hypothesis:
Increased hemorrhage at the site of medial collateral ligament injury improves healing.
Study Design:
Controlled laboratory study.
Methods:
Ninety-six mice were divided into two groups. Group 1 mice underwent knee medial collateral ligament transection with the opposite knee as a sham-operated control and group 2 animals additionally had 0.25 ml of tail cut blood pipetted to the medial collateral ligament transection site and sham-operated opposite knee. Ligament specimens were harvested at 3, 7, 21, and 28 days.
Results:
Immunohistochemical analysis demonstrated peak macrophage counts at day 7 in all transected specimens. Macrophage counts were higher in group 2 than in group 1 at all time points, with a statistically significant increase of macrophages noted at day 7. In situ hybridization demonstrated increased collagen gene expression, with peaks at 7 and 28 days after transection. Group 2 animals showed increased gene expression at all time points as compared with group 1, with a statistically significant increase noted at 7 and 28 days. Biomechanical testing demonstrated progressive healing at each time point. At 28 days, the load to failure was 67% that of the sham-operated knee.
Conclusions:
This study suggests there is an increased healing response with bleeding at the ligament injury site.
Clinical Relevance:
Identification of the factors involved with increased healing may allow manipulation of the healing response in the clinical setting.