Is Anterior Cruciate Ligament Repair Feasible?

Many authors in animal and in vitro studies investigated ACL biology and its healing response to injury. Rapid degeneration of ACL has been observed following acute rupture, which is associated with a significant increase in collagenase activity and a decrease in total collagen of the injured ligament. The poor healing abilities of ACL, when compared with the medial collateral ligament (MCL), are well known. The outgrowth of cells from ACL explants in vitro was slower than from MCL explants, as shown by the size of the surrounding clusters of cells, suggesting a lower proliferation and migration potential of ACL cells in comparison with MCL cells. In a rabbit model, a higher level of procollagen mRNA was consistently detected in normal MCL than in normal ACL, suggesting higher collagen synthetic activity in the MCL and possible differences in their healing capacities.

Comparing the healing response of ACL with other ligaments, the process of platelet fibrin clot formation of injured ACL is deranged/deficient. Without this clot, the wound remains opened and interferes with tissue remodeling and cellular migration, ultimately leading to nonhealing of the ruptured ligament. Presence of circulating plasmin in the joint space, which prematurely breaks down the fibrin clot, has been postulated to be the reason for lack of clot formation. Moreover, synovial fluid is also proven to inhibit ACL fibroblast proliferation and migration and thereby retard healing of tissue. Identification of strategies that could either form or aid in the formation of a scaffold between the tendon ends to address this problem has become an area of active research and investigation.

Primary Anterior Cruciate Ligament Repair—Healing Stimulation

The primary suture repair of the torn portions of the ACL was popularized in the 1950s. Long-term follow-up studies showed that these techniques presented failure rates up to 90% and were therefore abandoned. Despite these reports, recent investigations showed the possibility of ACL healing after primary suture of the ligament augmented with the use of growth factors and bone marrow–derived mesenchymal stem cells (MSCs). The potential advantages over ACLR technique are the preservation of the anatomy and kinematics of the ACL and knee proprioception, while donor site morbidity and muscular weakness are significantly reduced.

Cellular Therapies—Mesenchymal Stem Cells

The concept of “biological solutions for biological problems” has led to the development of less invasive procedures and accelerated treatments that in general reduce morbidity while enhancing functional recovery. Cellular therapies offer an interesting option in the treatment of injured ACL by addressing the defect in healing at a molecular level and leading to a biological means of healing. Steadman’s “healing response therapy” was one of the earliest treatments described, which extolled the role of MSCs in aiding the healing of a ruptured ACL in humans. The results of this therapy were reported as encouraging and were based on the multipotent nature of MSCs.

MSCs were initially isolated from bone marrow and since then have been reported to be isolated from a number of other tissues such as fat, muscle, skin, connective bone, and so on. The easy availability, coupled with the self-renewal capacity and multilineage differentiation potential of MSCs, has drawn the attention of researchers for various reasons. The phenotypic plasticity of these cells has generated considerable enthusiasm to use them in repairing or regenerating connective tissue with ex vivo, tissue engineering, or in situ techniques. The similarity between ACL outgrowth cells and MSCs gives the possibility to modulate these cells to enhance the healing of a repaired ACL.

Platelet Rich Plasma and Growth Factors

Bioactive proteins and growth factors play an important role in tissue healing, as they can regulate key processes in tissue repair, including cell proliferation, chemotaxis, migration, cellular differentiation, and extracellular matrix synthesis. Platelet rich plasma (PRP) contains many important growth factors that have been proven to enhance cellular proliferation and migration, as well as increased collagen production in in vitro studies. The rationale for the use of PRP is to stimulate the natural healing cascade and tissue regeneration by a “supra-physiologic” release of platelet-derived factors directly at the site of treatment. Autologous PRP can be obtained from simple blood extraction with a commercially available kit. Once the blood is collected into a tube containing anticoagulant, it undergoes a centrifugation process to produce PRP. Among the contained growth factors, PDGF, FGF, BMP, and TGF-β have shown to enhance the healing of ligaments.

Kobayashi et al. noted improved healing and vascularity following instillation of FGF in the canine ACL. Aspenberg and Forslund reported the use of GDF 5 in the Achilles tendon and showed improved healing. These growth factors can be used along with synthetic scaffolds to enhance the process of ACL repair. Chen reported the use of BMP 2 along with hydrogel and periosteum to stimulate tendon-bone healing in an ACLR model and showed that PPC-BMP-hydrogel composite is an effective inducer of healing and can act as a matrix for encapsulation of cell and growth factors. Murray et al. contested the role of PRP in ACL healing, following their results in skeletally immature animals in which they performed ACL repair with or without PRP injection. The addition of PRP to the suture repairs did not improve AP knee laxity maximum tensile load or linear stiffness of the ACL repairs after 14 weeks in vivo. The use of collagen-platelet composites has been shown to have beneficial effects as well.

Surgical Technique

The patients are placed supine under spinal anesthesia. After routine standard sterile preparation and draping, a complete examination of the knee stability is performed. A routine arthroscopic evaluation of the knee by standard anteromedial and anterolateral portals is performed, and partial tear of the ACL is confirmed. Associated pathologies of other intra-articular structures are addressed prior to ACL repair. ACL repair is performed by passing #1 polydioxanone sutures (Ethicon, Piscataway, New Jersey) using a Clever Hook or Express suture passer (DePuy Mitek, Raynham, Massachusetts) to suture together the torn portions of ACL and tied using a Duncan loop ( Fig. 96.1A ). Using a 45-degrees microfracture awl, several holes (1.5 mm in diameter, 3–4 mm apart, and 3 mm deep) are made around the anatomic femoral insertion of the ACL (see Fig. 96.1B ). PRP glue preparation is done using a commercially available system (Arthrex Angel System, Naples, Florida). Approximately 3 mL of PRP is isolated and activated with batroxobin enzyme (Plateltex act-S.R.O., Bratislava, Slovakia) to produce a sticky PRP gel, which is injected at the repaired site to biologically augment the healing process (see Fig. 96.1C ).

A, Primary repair of a partial anterior cruciate ligament (ACL) tear using a #1 polydioxanone suture. Asterisks on the left show partially torn ACL, asterisk on the right shows posterior cruciate ligament. B, ACL femoral footprint microfracture using a 45-degree microfracture awl. C, Growth factors injection at the femoral attachment of the repaired ACL.

Rehabilitation Protocol

All patients followed the same rehabilitation protocol. The knee was kept in a brace locked in extension for 3 weeks, and patients were allowed partial weight bearing with crutches, followed by weight bearing as tolerated. The postoperative brace is locked in full extension in order to avoid loss of extension; however, hyperextension should be avoided as well as active full extension against resistance (i.e., leg extensor machine). A continuous passive motion machine was used for 4–6 hours a day in a range between 20 and 60 degrees, starting the day after surgery. The range of motion (ROM) was increased up to 90 degrees by the end of 2 weeks and then gradually increased up to 120 degrees of flexion. Full active ROM was achieved between 6 and 12 weeks postoperation. Running was allowed at 3 months. No high-contact sports were allowed before 5 months.

Results

All patients were available at final follow-up. No infections or major postoperative complications were seen in this case series. Four patients (8%) had a retear during sporting activity and underwent ACLR within 2 years from primary repair surgery; their last evaluation scores were included in final results.

The difference in anterior translation of the knee compared with the unaffected side was reduced from 4.1 mm preoperatively to 1.4 mm at 5-years follow-up ( P < .05). A significant improvement in Tegner, SANE, Marx, Noyes, and Lysholm scores was observed at 5-years follow-up ( P < .05). The final International Knee Documentation Committee (IKDC) objective score was rated as normal in 39 patients (78%), nearly normal in 10 patients, and abnormal in 1 patient. The 11 patients with a nearly normal or abnormal IKDC scores had associated pathologies (meniscal or chondral lesions). Thirty-nine patients (78%) fully resumed sport activity. Return to previous sport activities was reached at a mean of 6 months after surgery. Eleven patients (22%) did not return to sport at preinjury level; in four of them, this was a personal choice.

Second-look arthroscopy was performed in six patients (12%) and revealed a healed ACL which was stable on probing and had minimal fibrous tissue ( Fig. 96.2A–D ).

Second-look arthroscopy of various patients at 4 weeks (A) , asterisks on the left show the healing of anterior cruciate ligament; asterisk on the right shows posterior cruciate ligament, 2 months (B) , 5 months (C) , and 8 months (D) ; follow-up: ligament continuity and stability as showed by probing.