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.
"There has been a recent upsurge in interest in using extracellular matrix-based materials to enhance repair of tissues within the knee joint. Specifically for the Anterior Cruciate Ligament (ACL), these materials have been used as platelet stabilization scaffolds in a central defect model [1, 2], as well as in a complete ACL transection model [3, 4] and also to enhance healing of an ACL reconstruction . In those studies, these materials appear promising with regards to improving the biomechanical strength of the repairs. "
[Show abstract][Hide abstract] ABSTRACT: Collagen is an important biomaterial in intra-articular tissue engineering, but there are unanswered questions about its safety. We hypothesize that the addition of type-I-collagen for primary repair of the Anterior Cruciate Ligament (ACL) might result in a local and systemic reaction in a porcine model after 15 weeks as demonstrated by joint effusion, synovial thickening, elevated intraarticular and systemic leukocyte counts. Further, this reaction might be aggravated by the addition of a platelet concentrate. Eighteen porcine ACLs were transected and repaired with either sutures (n=6), a collagen sponge (n=6), or a collagen-platelet-composite (CPC; n=6). Twelve intact contralateral knees served as controls (n=12). No significant synovial thickening or joint effusion was seen in the collagen-treated knees. Synovial fluid leukocyte counts showed no significant differences between surgically treated and intact knees, and no differences were seen in leukocyte counts of the peripheral blood. The addition of a platelet concentrate to the knee joint resulted in lower serum levels of IL-1β, but serum levels of TNF-α were not significantly different between groups. In conclusion, the presence of collagen, with or without added platelets, did not increase the local or systemic inflammatory reactions following surgery, suggesting that Type I collagen is safe to use in the knee joint.
The Open Orthopaedics Journal 06/2012; 6:231-8. DOI:10.2174/1874325001206010231
"The ligament tissue maturation index (LTMI) of Murray et al.  was used to evaluate the maturation of tendon grafts according to the following 3 criteria:  cellular aspects including cell density, nuclear shape, and orientation;  extracellular matrix characteristics, such as crimp; and  vascular features including blood vessel density and maturity (total score, 28 points). "
[Show abstract][Hide abstract] ABSTRACT: We developed a novel technique to improve tendon-bone attachment by hybridizing calcium phosphate (CaP) with a tendon graft using an alternate soaking process. However, the long-term result with regard to the interface between the tendon graft and the bone is unclear.
We analyzed bone tunnel enlargement by computed tomography and histological observation of the interface and the tendon graft with and without the CaP hybridization 2 years after anterior cruciate ligament (ACL) reconstruction in goats using EndoButton and the postscrew technique (CaP, n = 4; control, n = 4).
The tibial bone tunnel enlargement rates in the CaP group were lower than those in the control group (p < 0.05). In the CaP group, in the femoral and tibial bone tunnels at the anterior and posterior of the joint aperture site, direct insertion-like formation that contained a cartilage layer without tidemarks was more observed at the tendon-bone interface than in the control group (p < 0.05). Moreover, the gap area between the tendon graft and the bone was more observed at the femoral bone tunnel of the joint aperture site in the control group than in the CaP group (p < 0.05). The maturation of the tendon grafts determined using the ligament tissue maturation index was similar in both groups.
The CaP-hybridized tendon graft enhanced the tendon-bone healing 2 years after ACL reconstruction in goats. The use of CaP-hybridized tendon grafts can reduce the bone tunnel enlargement and gap area associated with the direct insertion-like formation in the interface near the joint.
Sports Medicine Arthroscopy Rehabilitation Therapy & Technology 12/2011; 3(1):31. DOI:10.1186/1758-2555-3-31
"Preliminary studies utilizing adalimumab (a tumor necrosis factor-alpha blocker), anakinra (an interleukin-1 antagonist)  or apronitin (a MMP-inhibitor)  or tropisetron (a 5-HT3 receptor antagonist with anti-inflammatory properties) have produced encouraging results . Local NO delivery, by means of glycerol trinitrate patches, has been proven to be beneficial by some authors, with reduction of pain and increases in strength in subjects with tennis elbow, Achilles TP and supraspinatus tendinosis , but other studies have failed to support its efficacy in Achilles TP [149,150]. A variety of materials have also been used in the formation of scaffolds, including natural components, such as collagen , as well as copolymers . "
[Show abstract][Hide abstract] ABSTRACT: The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies.
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