Page 23 - ISAKOS 2019 Newsletter Volume 1
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Because of the expected poor healing capabilities of the native ligament, the gold standard of treatment in cases of symptomatic ACL insufficiency is reconstruction of the damaged ligament with use of autograft or allograft tissue. While repair of the injured ACL potentially can provide expected long-term benefits, including the restoration of native joint kinematics, any repair procedure needs to adequately address the currently expected deficiencies of primary repair. Therefore, it is necessary to clearly delineate which ACL injury patterns are appropriate for such repair procedures.
The Role of Biologics
Transforming growth factor-beta1(TGF-β1), fibroblast growth factor-2 (FGF-2), growth and differentiation factors, and basic-FGF (bFGF) have been reported to regulate and improve cellular activities and proliferation, extracellular matrix (ECM) deposition, and influence the differentiation of mesenchymal stem cells (MSCs) into fibroblasts in the repair process of torn ligaments. Platelet-rich plasma (PRP) is known to contain a combination of bioactive agents that are capable of mediating tissue-healing processes during both the inflammatory and remodeling phases following an injury. Platelets are involved in homeostasis and clot formation, which are critically important components of tissue healing. These processes are mediated by the release of such factors as platelet-derived growth factor (PDGF), TGF-β1, vascular endothelial growth factor (VEGF), bFGF, and epidermal growth factor (EGF) through the degranulation of alpha granules. Among these growth factors, PDGF and TGF-β1 are particularly important modulators that contribute to increased fibroblast proliferation and collagen production during the healing process.
Cell therapy has been widely studied in vitro and in preclinical studies. Multipotent cells in the form of mesenchymal stem cells (MSCs) have been isolated from a number of tissues for clinical use, including bone marrow aspirate concentrate (BMAC) and lipoaspirate. An updated theory on the origins of mesenchymal stem cells has identified pericytes as the specialized cell of interest1. Pericytes reside alongside blood cells as a component of the perivascular niche. These cells become activated in response to injury, subsequently releasing a complex assortment of bioactive molecules and creating a microenvironment for tissue repair by stimulating regenerative processes and retarding aggressive immune responses that may impair the healing process.
ACL Repair with Biologic Augmentation
Steadman et al. pioneered biologic treatment of ACL injury by using a healing response procedure (microfracture of the intercondylar notch) to treat these injuries and reported their initial findings in a study of skeletally immature athletes2. This work was then expanded to include the treatment of ACL injuries in an older patient cohort3.
More recently, Gobbi et al. described a treatment method involving primary suture repair of the ACL combined with biologic augmentation. In their first report on this method, 26 athletes with symptomatic ACL insufficiency underwent primary repair and marrow stimulation and were followed for a mean of 25 months4. All patients had been diagnosed with incomplete proximal tears of the ACL and underwent surgical treatment within 4 weeks after the injury. High rates of return to the pre-injury level of activity were achieved as demonstrated by the mean Tegner and Marx scores at the time of the latest follow-up.
The mean side-to-side difference in anterior tibial translation decreased significantly, from 3.5 mm preoperatively to 1.3 mm postoperatively. In a subsequent study, 50 patients who underwent this treatment were assessed after an intermediate-term follow-up of 5 years5. At the time of the latest follow-up, 78% of the patients had returned to the pre-injury activity level, with postoperative IKDC objective scores being categorized as normal for 39 patients, nearly normal for 10 and severely abnormalin 1 patient. Recurrent ACL insufficiency was identified in 5 patients. Importantly, the technique of primary ligament repair and marrow stimulation may be further augmented by the addition of activated PRP and / or BMAC to the repair site, providing an array of critical bioactive molecules and cellular elements to help coordinate repair processes and to limit inflammatory responses that may be associated with degeneration of injured ligamentous tissue. Most recently, long-term outcomes (mean, 10 years; maximum, 14 years) have been examined after primary ACL repair with biologic augmentation (Gobbi et al., data submitted for publication). Activity levels at the final follow- up were comparable with the pre-injury status according to Tegner scores, and good to excellent outcomes were achieved according to IKDC subjective, Lysholm, and KOOS scores. Successful outcomes were also comparable between all types of partial ACL tears treated.
Surgical Technique: Primary ACL Repair with Biologic Augmentation (Fig. 1)
An examination is performed with the patient under anesthesia to identify instability consistent with ACL insufficiency. Diagnostic arthroscopy is then used to confirm the ACL injury and to characterize the specific injury pattern. ACL repair is performed by passing No. 1 PDS suture through the proximal and distal ligament segments of the torn bundle with use of an arthroscopic suture-passing device of the surgeon’s choice. Two to 3 sutures are typically passed for each repair. The sutures are tied arthroscopically, reapproximating and tensioning the disrupted bundle fibers. With use of a microfracture awl, several perforations are created within the notch, about the anatomic footprint of the ACL. Bone marrow aspirate is obtained from the ipsilateral iliac crest, and BMAC is isolated with use of a commercially available system.

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