With the known action of the matrix metalloproteinases and tissue inhibitors of metalloproteinase in extra-cellular matrix remodeling, these findings suggest that their roles in remodeling of rotator cuff tears should be further investigated.

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Injured ligaments heal with scar tissue, which has mechanical properties inferior to those of normal ligament, potentially resulting in re-injury, joint instability, and subsequent degenerative arthritis. In ligament scars, normal large-diameter collagen fibrils have been shown to be replaced by a homogenous population of small collagen fibrils. Because collagen is a major tensile load-bearing matrix element and because the proteoglycan decorin is known to inhibit collagen fibrillogenesis, we hypothesized that the restoration of larger collagen fibrils in a rabbit ligament scar, by down-regulating the proteoglycan decorin, would improve the mechanical properties of scar. In contrast to sense and injection-treated controls, in vivo treatment of injured ligament by antisense decorin oligodeoxynucleotides led to an increased development of larger collagen fibrils in early scar and a significant improvement in both scar failure strength (83-85% improvement at 6 weeks; p < 0.01) and scar creep elongation (33-48% less irrecoverable creep; p < 0.03) under loading. This is the first report that in vivo manipulation of collagen fibrillogenesis improves tissue function during repair processes with gene therapy. These findings not only suggest the potential use of this type of approach to improve the healing of various soft tissues (skin, ligament, tendon, and so on) but also support the use of such methods to better understand specific structure-function relationships in scars.

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The purpose of this study was to characterize the cellular organization of the ovine medial collateral ligament (MCL) and anterior cruciate ligament (ACL) and compare this organization with that found in ligaments undergoing healing. Indirect immunofluorescence microscopy, used in combination with antibodies to cytoskeletal proteins, was employed to visualize individual ligament cells. Normal ligaments contained fusiform cells arranged in rows, which were stacked at regular intervals across the body of the ligament forming a three-dimensional cellular lattice. Each cell exhibited prominent cytoplasmic processes that extended for long distances through the extracellular matrix to adjacent cells, and these processes contained gap junctions. Thus the cells in rows and between rows were interconnected. The cells of the MCL and ACL scars were also arranged in rows, but these rows were shorter, irregularly arranged and closely packed into bundles resulting in tissue with a higher cellular density. In addition, cells transiting the cell cycle were detected in the scar but not in normal ligament. While the rows of cells in the normal ligament extended along the long axis of the ligament, the bundles of rows of ligament scar cells had a random orientation with respect to one another and to the region outside the scar. Over time both the ACL and the MCL scars displayed discontinuities in their cellular rows. In contrast to the scars of the MCL, which contained discontinuities filled with cellular projections and gap junctions, ACL scars contained discontinuities that were devoid of cells and gap junctions. These discontinuities as well as the differences between normal and scar cytoarchitecture may represent features of an inadequate healing response and/or may provide the structural basis for the altered biomechanics of healing ligaments.

The objective of this study was to use an ovine stifle joint model to assess the impact of combined transection of the anterior cruciate and medial collateral ligaments on three-dimensional (3D) joint motion serially over 20 weeks after transection. In vivo 3D kinematics were measured in the right hind limb of eight sheep while walking on a treadmill (accuracy, 0.4 mm AE 0.4 mm, 0.48 AE 0.48). Five sheep received surgical ligament transection and three sheep received sham surgery without transection. At 2 weeks after transection, average joint flexion at hoof strike was significantly increased (8.98 AE 3.08), and the tibial position was significantly shifted in the anterior direction relative to the femur during midstance (4.9 mm AE 0.9 mm). By 20 weeks after transection, joint flexion had normalized, but the tibial position was significantly adducted (0.58 AE 0.78) and shifted in the medial (2.5 mm AE 1.2 mm), anterior (5.8 mm AE 1.9 mm), and superior directions (1.6 mm AE 0.4 mm). At 2 and 20 weeks after surgical intervention, the maximal anterior tibial position was significantly increased during mid-stance in the transected group (4.9 mm AE 0. 9 mm and 5.8 mm AE 1.9 mm) compared to the sham operated group (0.2 mm AE 0.2 mm and À0.1 AE 0.1 mm). Although the anterior tibial shift was observed in all transected sheep, a high degree of variability existed between sheep, in the intitial joint position, the magnitude of the early change, the change over time, and the change at 20 weeks. In this situation statistics must be interpreted carefully, and in future studies, individual changes should be assessed in the context of individual pathological changes in order to investigate potential clinical significance. ß

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