Effect of hemorrhage on medial collateral ligament healing in a mouse model

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 mi 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.