2.6.1 Recent clinical attempts
Surgeons have pursued new interventions that could increase healing ACL tissue formation and improve knee stability [95, 234-236]. One such treatment is biological augmentation of the injured ACL by creating small holes in the bone (microfractures) near the femoral insertion of the ACL to introduce bone marrow and blood to the injury site. This allows formation of a blood clots in order to elicit a healing response more similar to the healing of extra-articular ligaments. These procedures have proved to be mostly successful to treat ACL tears near the femoral insertion site. Over 95% of patients over 40 years of age had restoration of knee function with little pain in the short-term [235]. Positive results were also obtained for younger, skeletally immature patients. However, 23% of these patients were had reinjuries that required additional intervention [94, 234]. Nevertheless, the clinical evidence for the potential of ACL healing is indeed encouraging, and suggests that additional laboratory studies should be done to improve on these early results.
2.6.2 Basic science studies
Laboratory research has also shown that ACL cells can be stimulated through the use of scaffolds and growth factors [127, 144, 163, 165-168, 214, 279]. These positive findings have motivated in-vivo treatment of partial ACL injuries in animal models with a variety of different approaches, including the application of bFGF, hyaluronic acid, and cell therapy using bone marrow-derived mesenchymal stem cells [10, 127, 252]. Based on histomorphological
assessments in the short-term, these approaches generally revealed more tissue growth, vascularity at the injury site, and better matrix organization compared to the non-treated injury. However, all treated ACLs remained considerably abnormal in terms of their morphology and biomechanical properties when compared to the normal ACL.
More recently, Murray and coworkers have developed the use of a platelet-rich plasma (PRP) hydrogel to treat ACL injuries, which is intended to simulate a healing clot. Interestingly, a completely transected ACL with PRP treatment in combination with suture repair only minimally improved over suture repair alone even at 14 weeks post surgery [165]. The authors have suggested the need for additional scaffolding and have developed a collagen-platelet rich plasma (C-PRP) scaffold to treat a partial ACL tear in a canine model [168] as well as a complete ACL transection in a porcine model following suture repair [118, 162, 165, 167]. In the canine partial ACL tear model, histological evidence of more healing tissue filling the injury site as well as improved biomechanical properties were found compared to non-treatment at 6 weeks [168]. The C-PRP hydrogel was then extended to a full ACL transection model in pigs, which revealed that ACL healing took place at 4 weeks but with hypertrophic neo-tissue formation as measured by MRI [167]. Tensile testing of the healing femur-ACL-tibia complexes (FATCs) also showed significant improvements in its tensile stiffness and ultimate load. By 3 months, treatment with a collagen-platelet composite (CPC) and suture repair led to a 3 fold increase in the stiffness of the healing FATCs compared to suture repair alone. Thus, these findings on ACL healing are extremely encouraging.
However, it should also be noted that the biomechanical properties of the healing ACL were still well below those of a normal ACL. In addition, excessive hypertrophy of the healing
healing tissue and its level of contribution to joint function, which was not tested. Thus, there is still a need for novel FTE solutions to induce appropriate tissue growth while limiting its hypertrophy to bring about a much improved healing ACL and joint stability.
2.6.3 Suture techniques in combination with FTE
In order to achieve the needed joint stability during the early healing process, these new biological approaches are often coupled with suture repair and/or augmentation of the torn ends of the ACL [61, 120, 167, 184, 218, 248]. As previously mentioned, the goals of suture repair are to reapproximate the torn ends of the ACL to permit healing as well as to restore initial joint stability. Most techniques involve suturing of each tissue stump and passing these sutures through bone tunnels created in the tibia and femur and fixed to the outer bony cortex.
A recent study by Fleming and coworkers has shown that suture repair of the ACL tissue alone is insufficient to restore anterior-posterior knee [73]. The authors hypothesize that this is likely due to sliding of the sutures relative to the soft tissue as well as the difficulty in applying tension to the sutures. Alternatively, augmentation of the injured ACL, by passing sutures directly from bone to bone, has been suggested in combination with suture repair to better restore knee stability while also reapproximating the ACL tissue stumps. In this approach, the augmentation sutures would provide bone to bone fixation, and thus, would greatly reduce the possibility of sliding and allow proper tensioning. In fact, Fleming and coworkers found that this technique could better restore anterior-posterior knee stability compared to suture repair [73].
However, there are a number of limitations in this study, including 1) only 1 degree-of- freedom motion [111], 2) assessment of knee stability at only one flexion angle (60 degrees), 3)
the outcome of these suture techniques after healing. All of these concerns can be addressed by combining in-vivo animal studies with a robotic testing system to assess joint function.