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

Abstract

Medial collateral ligament injuries heal by a scar response. Increased hemorrhage at the site of medial collateral ligament injury improves healing. Controlled laboratory study. 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. 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. This study suggests there is an increased healing response with bleeding at the ligament injury site. Identification of the factors involved with increased healing may allow manipulation of the healing response in the clinical setting.