The anterior cruciate ligament (ACL) of the knee is an intra-articular ligament that fails to heal after primary repair. The medial collateral ligament (MCL) of the knee is an extra-articular ligament that heals uneventfully in the majority of cases. Why these two ligaments have such different responses to injury remains unclear. In this article, we address two hypotheses: first, that the histologic response to injury is different in intra-articular and extra-articular ligaments, and second, that the response of the intra-articular ligaments can be altered by placing a collagen-platelet-rich plasma (collagen-PRP) hydrogel in the wound site. Wounds were created in extra-articular ligaments (MCL and/or patellar ligament) and an intra-articular ligament (ACL) in canine knees, and the histologic response to injury evaluated at 3 days (n = 3), 7 days (n = 4), 3 weeks (n = 5), and 6 weeks (n = 5). In the 3-week (n = 5) and 6-week (n = 5) animals, bilateral central wounds were made in the ACLs and the wounds in one knee of each animal treated with a collagen-PRP hydrogel while the contralateral side was untreated. Extra-articular ligament wounds had greater filling of the wound site and increased presence in the wound site of fibrinogen, fibronectin, PDGF-A, TGF-beta1, FGF-2, and von Willebrand's factor when compared to intra-articular ligament wounds. Treatment of the intra-articular wound with a collagen-PRP hydrogel resulted in increased filling of the wound site with repair tissue that had similar profiles of growth factor and protein expression to the extra-articular ligament wounds. The use of a collagen-PRP scaffold can ameliorate histologic differences noted between healing extra-articular ligamentous wounds and nonhealing intra-articular ligamentous wounds. This study supports the hypothesis that premature scaffold failure may play a key role in the normally expected failure of the ACL to heal after injury.

The anterior cruciate ligament (ACL) of the knee fails to heal after primary repair. Here we hypothesize that a beneficial biologic repair response can be induced by placing a collagen-platelet rich plasma (collagen-PRP) material into a central ACL defect. A collagen-PRP scaffold was used to treat a central ACL defect in vivo. In the first experiment, the histologic response in treated and untreated defects was evaluated at 3 (n ¼ 5) and 6 weeks (n ¼ 5). In the second experiment, biomechanical testing of the treated ligaments (n ¼ 8) was performed at 6 weeks and compared with the results of biomechanical testing of untreated defects at the same time-point (n ¼ 6). The percentage filling of the defects in the treated ACLs was significantly higher at both the 3-and 6-week time-points when compared with the untreated contralateral control defects (50 AE 21% vs. 2 AE 2% at 3 weeks, and 43 AE 11% vs. 23 AE 11 at 6 weeks; all values mean AE SEM. Biomechanically, the treated ACL defects had a 40% increase in strength at 6 weeks, which was significantly higher than the 14% increase in strength previously reported for untreated defects ( p < 0.02). Placement of a collagen-PRP bridging scaffold in a central ACL defect can stimulate healing of the ACL histologically and biomechanically. ß