Costa et al. Journal of Experimental Orthopaedics (2022) 9:26 Journal of https://doi.org/10.1186/s40634-022-00461-3 Experimental Orthopaedics REVIEW PAPER Open Access Minimizing the risk of graft failure after anterior cruciate ligament reconstruction in athletes. A narrative review of the current evidence Giuseppe Gianluca Costa1,2* , Simone Perelli2,3, Alberto Grassi4, Arcangelo Russo1, Stefano Zaffagnini4 and Juan Carlos Monllau2,3 Abstract Anterior cruciate ligament (ACL) tear is one of the most common sport-related injuries and the request for ACL recon- structions is increasing nowadays. Unfortunately, ACL graft failures are reported in up to 34.2% in athletes, represent- ing a traumatic and career-threatening event. It can be convenient to understand the various risk factors for ACL failure, in order to properly inform the patients about the expected outcomes and to minimize the chance of poor results. In literature, a multitude of studies have been performed on the failure risks after ACL reconstruction, but the huge amount of data may generate much confusion. The aim of this review is to resume the data collected from literature on the risk of graft failure after ACL reconstruc- tion in athletes, focusing on the following three key points: individuate the predisposing factors to ACL reconstruction failure, analyze surgical aspects which may have significant impact on outcomes, highlight the current criteria regard- ing safe return to sport after ACL reconstruction. Keywords: Anterior cruciate ligament reconstruction, Failure, Prevention, Surgical technique, Return to sport, Athletes Introduction Despite the recent advances in arthroscopic equipment, Anterior cruciate ligament (ACL) tear is one of the most understanding knee biomechanics and surgical tech- common sport-related injuries, involving about 3% of niques, unfortunately ACL reconstruction is not always amateur athletes every year, and up to 15% of elite ath- successful, but a significant number of patients (10% to letes per year [87]. The international literature unani- 15%) [116] reports unsatisfactory outcomes. Previous mously agrees on the importance of performing surgical systematic reviews reported only 60% of amateur athletes reconstruction in active patients, in order to properly [5] and 83% of elite athletes [62] returned to their prein- restore the joint kinematics, preserve the intraarticular jury sport level after ACL reconstruction. Graft failure is knee structures and increase the likelihood to resume one of the main determinants of outcomes, representing preinjury sport activities [50, 58, 101]. a traumatic and career-threatening event in athletes. In a meta-analysis involving 1272 elite athletes, the pooled failure rate was estimated in 5.2% (range 2.8% - 19.3%) [62], but this rate has been shown to grow up to 34.2% *Correspondence: gianlucacosta@hotmail.it 1 Orthopaedic and Traumatologic Unit, Umberto I Hospital, Azienda when including high-risk cohorts like younger athletes Sanitaria Provinciale di Enna, C.da Ferrante, 94100 Enna, Italy [142]. The outcomes after revision ACL reconstructions Full list of author information is available at the end of the article © The Author(s) 2022. 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Journal of Experimental Orthopaedics (2022) 9:26 Page 2 of 14 are shown not as good as primary reconstructions, in joint laxity. This joint laxity could alter dynamics of lower terms of functional scores, rotatory stability, and risk of limbs motions and predispose to failure [59]. developing knee osteoarthritis [39, 89]. If the evidence for age can be defined as high, the same It can be convenient to understand the multiple risk cannot be stated for patient gender as significant fac- factors for ACL graft failure, in order to properly inform tor. Some registry studies demonstrated a higher risk for the patients about the expected outcomes and to mini- ACL revision in male patients [16, 130], whereas other mize the chance of poor results. In literature, a multi- registry data deny this finding, reporting a greater risk tude of studies have been performed on the risk factors in female patients [2]. In addition, several other similar of failure after ACL reconstruction, but the huge amount studies failed to demonstrate a statistically significant of data may generate conflicting evidence. A compre- relationship between patient gender and ACL revision hensive analysis of this information may support those [55, 73, 111]. A recent meta-analysis including 135 arti- who want to approach this issue with an evidence-based cles showed that graft failure rates did not differ signifi- methodology. cantly between sexes [132]. However, the inclusion of a The aim of the current review is to examine data col- such impressive number of studies is not immune from lected from literature about the risk of graft failure after plausible confounders, such as differences in activity level ACL reconstruction in athletes, focusing on the following or age distribution of the groups. The anthropometric three key points: (1) identify the predisposing factors to sex-based differences, as well as sex hormonal influence ACL reconstruction failure, (2) analyze surgical aspects deserve further investigation with higher methodological which may have significant impact on outcomes, and quality. (3) highlight the current criteria regarding safe return to sport after ACL reconstruction. Anatomical factors Several anatomical factors have been directly correlated Predisposing factors with increased rate of ACL injury but there is poor evi- Identifying predisposing factors for graft failures can rep- dence about the correlation of such anatomical patterns resent a successful approach for several reasons. First, and risk of graft failure after ACL reconstruction. This is patients can be better informed about the chances of especially true for the body mass index (BMI). Two reg- failure after an ACL reconstruction. Secondly, this infor- istry studies on 12,643 patients [108] and 21,304 patients mation can be used for developing strategies to modify [81], respectively, found a lower risk for ACL revision manipulable factors and, therefore, reduce the risk of fail- in patients with higher BMI. In contrast, a cohort study ure. For convenience, predisposing factors will be clas- on 30,747 patients from the Norwegian and the Swedish sified as demographic, anatomical and environmental National Knee Ligament Registries reported an increased factors. risk for ACL revision within 2 years both in male and female patients with higher BMI [125]. However, this Demographic factors risk was higher especially for those patients with BMI Age is universally recognized as independent factor between 25 and 30, whereas it significantly decreased affecting risk for ACL graft failure. In a recent systematic in patients with a BMI > 30. The different neuromuscu- review including 33 studies from 4 different national reg- lar control as well as the patients’ level of participation istries [111], young age was reported as independent risk in sport activity might affect the validity of this line of factor for revision ACL surgery in all registries. Patients research, but on the other hand, can represent a convinc- aged under 20 years were found to have a risk three ing explanation of such findings. times higher than patients over 20 years old, four times Another interesting chapter is the relationship between higher when compared to patients over 30 years old and bony knee anatomy and risk for graft failure. nearly eight times higher than patients aged 40 years or Several anatomical features have been invoked over older [111]. In another prospective analysis of 2488 pri- the years, including the lateral tibial slope, the intercon- mary ACL reconstructions, the authors found that the dylar notch, the lateral femoral condylar offset, the alpha likelihood of failure decreased by 9% for each increas- angle (that is the angle between the longitudinal axis of ing year of patients’ age [58]. One of the reasons may the femur and the Blumensaat line), the lateral femoral be the higher activity level in younger patients, which is notch sign depth, the tibial eminence size, the lateral tib- shown to significantly affect the risk of reinjury [55]. In ial plateau diameter, and many others [9]. All these bony addition, Nakanishi et al. [98] evaluated the anteroposte- morphologic features have been advocated as predispos- rior stability with arthrometric testing of two groups of ing factors for native ACL rupture, but their effect on the patients undergoing ACL reconstruction and found that risk of graft failure remains indefinite [42]. Among these, younger group had a greater tendency for residual knee the lateral tibial slope (Fig. 1) has gained more attention Costa et al. Journal of Experimental Orthopaedics (2022) 9:26 Page 3 of 14 rotation movements [36]. However, some recent studies on human cadaveric knees [53] and post-operative imag- ing analysis [42, 52, 144] demonstrated that, if the graft is correctly placed, impingement should not occur, and therefore the risk for failure is not increased. Environmental factors Environmental factors include both extrinsic aspects to athlete (such as type of resumed sport, playing surface, footwear etc.) and biomechanical aspects of playing actions which may predispose to graft retear. Since all those are modifiable factors, large research efforts have been made to create preventive programs focused on these issues [4]. Participation in pivoting and hard cutting sports is a well-known predictor of further graft tear after ACL reconstruction. It is estimated a four-times increased risk of knee reinjury among athletes of such sports activi- ties [44]. However, modifying activity level is not always suitable, because intent to return to high level sports is often the main reason why a patient with an ACL tear undergoes arthroscopic reconstruction. Therefore, spe- cific sessions including plyometric exercise, neuromus- cular reeducation, balance and strength training have been advocated to prevent knee reinjuries [44, 99]. For instance, dynamic valgus collapse during weightbearing activities (such as cutting, landing or changing direction movements) was found to be predictor of non-contact ACL injury [43]. This may be due to specific muscular Fig. 1 The lateral posterior tibial slope, that is the angle between the weakness (hip abductors, knee flexors) as well as some tangential line to the surface of the lateral tibial plateau (line AB) and predisposing anatomical features, such as increased fem- the perpendicular to the tibial axis (line AC) oral anteversion or external tibial torsion [120]. A proper balance between quadriceps and hamstring activation is critical to not overload the knee during the landing after among physicians in the last few years. A study on human a jump. Specifically, hamstring recruitment reduces ACL cadavers reported that an increased lateral tibial slope loads at landing [143] and may help to provide dynamic was significantly associated with anterior tibial accelera- knee stability by resisting anterior tibial translation and tion and ACL strain during simulated jump landing task rotations [67]. Based on this, several interventional stud- [11]. Several studies found a significantly higher value ies describing specific neuromuscular and plyometric of lateral tibial slope among patients with a failed ACL prevention programs demonstrated a significant reduc- reconstruction, when compared to patients who did not tion in the incidence of ACL injuries [4, 44, 99]. experience graft failure after reconstruction [19, 42, 45, 54, 115, 148]. Considering this background, some authors Surgical procedure advocated a combined closing-wedge anterior high tibial Graft failure after ACL reconstruction may result from osteotomy in cases of multiple ACL reconstruction fail- any combination of technical errors, biologic causes ures in the absence of technical errors and with a radio- and traumatic events. Historically, technical errors have graphic lateral tibial slope > 12° [72]. been considered the most important cause of graft fail- The evidence regarding the effect of the remaining ana- ure [139]. A recent systematic review [139] conducted tomical variables on the risk of ACL graft failure is poor. on 3567 failures identified technical errors as one of the This is also true for the intercondylar notch, discussed most common causes of failure, preceded only by trau- as early as 1980s [9]. Theoretically, a small intercondy- matic events. Similarly, Karmath et al. [56] reviewed the lar notch could create wear of the graft on the lateral literature regarding outcomes after ACL reconstruction femoral condyle during knee extension and internal and reported that technical errors (e.g., improper tunnel Costa et al. Journal of Experimental Orthopaedics (2022) 9:26 Page 4 of 14 placement, inadequate ACL graft, insufficient graft ten- Based on such evidence, international literature sup- sioning and failure to recognize concomitant laxity) ports such additional procedures in high-risk patients. accounted for 22% to 79% of failure cases. Therefore, it Indications include patients with high-grade pivot shift, should not be surprising that technical aspects of ACL concomitant Segond fractures, high-level athletes par- reconstruction have always been a major focus for scien- ticipating in pivoting sports and in ACL revision settings tific investigation. With the aim to provide an exhaustive [127]. synthesis of the huge amount of data published in the lit- Medial collateral ligament (MCL) injury is frequently erature, this section will focus on the proper management associated to ACL tears [38], as a result of the valgus of concomitant lesions, the outcomes related to different stress component of a typical ACL trauma. ACL and graft types and the evidence about surgical technique. MCL play a concomitant role in maintaining anterome- dial knee stability [141]. Several cadaveric studies dem- Concomitant lesions management onstrated that ACL strain is increased after sectioning When planning an ACL reconstruction, an assessment of MCL, when applying a valgus stress or an intra-rotation the other ligaments as well as intra-articular structures of movement of the tibia [8, 141]. In addition, combined the knee should not be omitted. Associated lesions can MCL and ACL sectioning increases anterior knee laxity compromise the graft function due to residual instabil- greater than isolated ACL sectioning [80]. Despite these ity. It is estimated that about 15% of ACL reconstruction findings, the treatment of combined ACL and MCL tears failures can be result of a missing diagnosis of associated is still controversial. Most authors support the conserva- ligament or meniscus lesion at time of surgery [34, 116]. tive management of the MCL injury, especially in acute One of the most discussed issues about this topic is settings and low-grade injuries [12, 38]. A “wait and see” the protective effect of the anterolateral ligament (ALL) approach is recommended by some authors also in high- on the ACL graft function. This interest is fueled by the grade MCL tears [38]. However, a recent study from the common finding of residual pivot-shift phenomenon Swedish National Knee Ligament Registry highlighted a after ACL reconstruction, which is estimated in up to higher risk of ACL revision in patients with ACL recon- 25% of cases regardless the chosen graft [127]. Further- struction and non-surgically treated MCL injuries com- more, persisting rotational instability has been shown pared to isolated ACL reconstructions [131]. When a to be a risk factor for recurrent injuries and ACL failure repair or reconstruction of concomitant MCL injuries [127]. Anterior translation, internal rotation, and pivot was performed, this risk was comparable to isolated shift was found to be better restored with combined ACL reconstructions [131]. These findings encourage the ACL/ALL reconstruction than with ACL reconstruction authors supporting early MCL repair or reconstruction alone in several biomechanical studies [60]. Lateral extra- [27] because ACL insufficiency might adversely affect the articular tenodesis (LET) procedures have also been MCL process healing [145]. On the other hand, delayed found effective in reducing tibial internal rotation and ACL reconstructions have been related to better func- intra-articular ACL graft force [122], although the risk tional outcomes with earlier motion recovery [90]. MCL of knee overconstraint has been reported [122]. This can surgical treatment should be considered in patients with be reduced if the graft is attached proximal to the lateral severe valgus alignment, entrapment over the pes anseri- epicondyle and courses deep to the fibular collateral liga- nus tendon (Stener-like lesion), large bony avulsions and ment [122]. persistent instability after ACL reconstruction [27, 90]. Such biomechanical findings also result in clinical The posterolateral corner (PLC) of the knee is another evidence of reduced risk of graft failure [93]. A recent important issue of academic interest, because of an evolv- meta-analysis of 20 randomized and nonrandomized ing appreciation for its biomechanical relationship with controlled trials found that the rate of graft failure was the ACL. PLC injuries are commonly associated to cru- two-to-four times lower in the ACL plus ALL recon- ciate ligaments tears, occurring in isolation in only 28% struction/LET group than in the isolated ACL recon- of cases [25]. Specifically, 7.4% - 13.9% of patients with struction group, regardless the adopted technique or the ACL injury have a concomitant PLC injury [64]. Biome- surgical timing [94]. In contrast to ALL reconstruction chanical data demonstrated a significant increase in force techniques, patients who underwent LET combined with on the ACL in PLC-deficient knee, when applying a varus ACL reconstruction were found to be more prone to suf- moment or a combined varus-internal rotation moment fer of knee stiffness and adverse events [95]. In another to the knee joint [63, 109], as well as during simulated meta-analysis including 7 randomized controlled trials, gait and squatting [57]. In addition, Plaweski et al. [109] graft failure rate was 3 times less likely in patients who found that an ACL reconstruction was not enough to underwent an ACL reconstruction with LET when com- prevent varus and external rotation displacement in the pared to patients with isolated ACL reconstruction [104]. setting of ACL-PLC deficient knee; a return to native Costa et al. Journal of Experimental Orthopaedics (2022) 9:26 Page 5 of 14 kinematics was achieved only after adding a reconstruc- subluxation of the lateral compartment in patients with tion of PLC static structures. Despite such promises, ACL injuries [153]. Similarly, medial MPRLs were found the role of PLC on the risk of ACL failure has not been to significantly increase ACL graft loads over the intact adequately investigated. In one registry study, a con- state, while root repair restored the function of the comitant PLC injury would appear to not affect the risk medial meniscus as a secondary stabilizer [117]. Finally, of ACL failure, whatever the treatment is [131]. However, a ramp lesion in an ACL-deficient knee has also been this analysis was impaired by the small size of the study shown to increase anterior tibial translation and external groups, which limits the relevance of such findings. rotational laxities [95, 129]. This aberrant laxity cannot be At last but not least, the biomechanical influence of completely restored after ACL reconstruction alone but the menisci on knee stability must not be overlooked. It with combined posterior menisco-capsular repair (Fig. 3) is well known that the medial and lateral menisci con- [96]. Nevertheless, there is poor clinical evidence regard- tribute to knee stability, acting as secondary restraints ing increased risk of graft failure following meniscal loss. for anterior and rotatory tibial displacement [41, 46, Only one study identified medial or lateral meniscus defi- 94]. Meniscus repair would seem to restore knee sta- ciency as significant factor for predicting graft failure bility comparable to ACL-reconstructed knees with [107], while several other studies did not detect signifi- intact menisci [46]. These findings also apply to menis- cant difference between isolated ACL reconstruction and cus posterior root lesions (MPRL) [117, 153]. Lateral ACL reconstruction combined with medial and/or lateral MPRLs (Fig. 2) were reported to increase anterior tibial meniscectomy [3, 111, 149]. However, meniscectomy has been clearly recognized as a risk factor for delayed return to sport [3] and career shortening in athletes [3, 13, 100]. As a result, meniscus repair should be considered even in athletes. Graft choice Graft choice has always been one of the most critical top- ics for discussion. The “ideal graft” used for surgical ACL reconstruction should recreate, as far as possible, the bio- mechanical properties of the native ligament, providing rapid biological integration and reducing recovery. Historically, autologous grafts have been considered as the first-choice graft [6], since allografts and syn- thetic grafts have been proved to be inferior in terms of failure rates, clinical scores, and knee stability [23, 32, 48, 49, 111], especially among younger patients [23, 48]. Actually, bone-patellar tendon-bone (BPTB) is the over- Fig. 2 Lateral posterior meniscus root lesion, which are reported whelming favorite over hamstring grafts in athletic pop- to significantly increase the anterior tibial subluxation of the lateral compartment in patients with ACL injuries ulation [40, 82], although quadriceps tendon (QT) has Fig. 3 The ramp lesion, defined as posteromedial meniscocapsular disjunction and visualized with trans-notch view (A). The meniscocapsular repair with all-inside technique helps to restore native knee kinematics in concomitant ACL tears (B) Costa et al. Journal of Experimental Orthopaedics (2022) 9:26 Page 6 of 14 renewed interest among physicians as a potential alterna- was overturned when a suspensory femoral fixation was tive [6]. used in hamstring group. This led to the suggestion that The available evidence in literature is mixed on which graft fixation is also an important aspect of surgical fail- graft type is associated with a higher risk of graft failure ure. Surprisingly, a recent registry study from the Dan- and revision ACL reconstruction. In a systematic review ish Knee Ligament Registry [75] reported a statistically conducted in 2017 and including all available meta-anal- significant higher risk of failure for QT graft (4.7%) in yses focused on comparison between BPTB and ham- comparison to both BPTB (1.5%) and hamstrings graft string grafts [119], the authors found that 10 out of 13 (2.3%) at 2-year follow up. However, the smaller samples meta-analyses failed to demonstrate statistically signifi- size, the lower patients’ age and the higher incidence of cance between the two groups regarding the graft fail- concomitant meniscus and cartilage injuries in the QT ure rate. More recently, a systematic review exclusively cohort represent a relevant bias. In addition to this, the involving athletic population [26] demonstrated similar same authors revealed the considerable influence of the failure rates between BPTB (2.2%) and hamstring auto- learning curve on the outcomes of ACL reconstruction grafts (2.5%), but a trend for higher return to sport rates with QT, since revision rates dropped to 0.8–2.0% when was found in athletes with BPTB autografts (81%) when low volume clinics with less than 100 procedures per compared with hamstring autografts (70.6%). The asso- years were excluded [74]. ciation between graft choice and the rate of revision has As it can be deduced from all these data, there is no also been investigated in several registry studies [111]. In evidence regarding superiority of one autograft over the a systematic review collecting data from 11 registry stud- others. Each graft presents both advantages and issues ies [111], a statistically significant lower revision risk in that need to be considered. For example, BPTB auto- favour of BPTB in comparison to hamstring grafts was grafts have some well-documented morbidities includ- reported in nine out of eleven studies. This reduced risk ing postoperative anterior knee pain, difficulty kneeling, seemed to be slightly more pronounced for younger and the risk of extension deficit [93, 113, 119]. On the patients and for athletes involved in pivoting activities, other hand, proponents of hamstring autografts reported such as soccer, team handball, and alpine activities [111]. less donor-site morbidity, but increased weakness in hip However, when interpreting such data, the influence of extension and terminal knee flexion, as well as variable some confounding bias needs to be considered, firstly the outcomes related to graft size and length [93]. If the ham- role of surgery volume. It has been previously demon- string graft size is equal or less than 8 mm, the risk of fail- strated that lower volume surgeons in lower volume hos- ure was found to increase by 6.8 times [22]. Despite some pital prefer hamstrings over BPTB autografts [51]. Lower fascinating biomechanical promises, QT graft remains volume sites have been associated with more patient- the least studied and least used autograft [88]. The lack reported subjective failures of ACL reconstruction [84] of long-term trials makes the QT a difficult choice for and subsequent revision surgeries [79]. Finally, a recent surgeons, who prefer grafts that have been shown to be meta-analysis [7] pointed out a higher incidence of deep safe and clinically efficient in the long term. As a result of infections after ACL reconstruction with hamstring auto- what has been said, it is reasonable to make an individual grafts compared with BPTB autografts. Although it is an graft choice, based on patient’s expectation, body charac- unusual complication, it should deserve particular con- teristics and kind of sport resumed. sideration because of the potentially deleterious effects on graft function, knee joint and athletes’ career, taking Surgical technique into account that professional athletes are defined as a Proper positioning of the ACL graft has been proven to risk category [128]. be of utmost importance to reduce risk of graft failure Outcomes of QT graft were evaluated in three recent [92, 139]. Non-anatomic graft positions create not physi- meta-analyses [93, 102, 113]. Riaz et al. [113] firstly ological intra-articular force vectors, which may affect demonstrates comparable survival rates and joint stabil- graft longevity. For instance, a graft that is placed too ity when BPTB and QT grafts are used, but with fewer posterior or too low in the femoral condyle edge is sub- adverse donor site symptoms using QT grafts. Later, such jected to higher tension during knee extension [83]. Con- findings were confirmed by Mouarbes et al. [93] in a sys- versely, a high and anterior position produces a longer tematic review of 2856 patients, reporting QT grafts have and more “vertical” graft, which results in increased ante- comparable graft survival rate to BPTB and hamstring, rior tibial translation [1] and increased rotational laxity with less harvest site pain than BPTB autograft and bet- [66, 150]. In addition to the above, graft positioning also ter functional outcome scores than hamstring autograft. influences the risk of graft impingement [105]. This may Nyland et al. [102] found that QT autografts had lower impact not only knee motion, but also risk of graft fail- failure rates than hamstring autografts, but difference ure [47]. According to the above, it is recommendable Costa et al. Journal of Experimental Orthopaedics (2022) 9:26 Page 7 of 14 to place femoral and tibial tunnels as close to the native [133]. This angle was demonstrated to significantly affect ACL footprints as possible, in order to reproduce more the graft signal and femoral tunnel diameter at 12 months closely the biomechanical properties of the native ACL [68], although the clinical relevance of such finding is [10, 92, 150]. unclear, because functional outcomes, arthrometric data The transtibial technique makes it more difficult to and subjective scores seem to not be related [68]. Finally, address accurately and reliably the femoral ACL foot- the learning curve of the more demanding “tibial tunnel- print [65]. As a result, several physicians support tibial independent” has been advocated as part of the explana- tunnel-independent methods for femoral tunnel place- tion of such findings [112], although the anteromedial ment, which have been proven to provide a more ana- portal method has been reported as the most used tech- tomic positioning of both the tibial and femoral tunnels nique for femoral tunnel drilling throughout the world (Fig. 4) [65, 114]. In accordance with such biomechani- [88]. With improved understanding of the anatomy cal evidence, international literature demonstrated that and biomechanics of the ACL, the transtibial approach tibial tunnel-independent techniques result in better has been modified to achieve a more anatomic femoral knee stability and functional outcomes [18, 78, 90, 114]. tunnel placement. The modified transtibial technique Accordingly, these techniques should better protect the showed superior outcomes than conventional transtibial knee from further joint injuries [30] and osteoarthritis approach and comparable with the anteromedial portal development [20]. This was confirmed by a recent meta- technique in terms of clinical scores, negative rates of analysis including a total of 1546 patients [20], but such the Lachman and the pivot-shift test, and return-to-sport findings are affected by the lack of a more in-depth analy- level [69]. Future studies are needed to determine the sis of concomitant meniscal injuries, thus representing long-term benefits with the modified transtibial in terms a relevant bias that may have influenced the observed of graft failure rates. rates of osteoarthritis development. Despite this, there In addition to the above, alternative techniques have is no evidence of lower subjective outcomes scores [18, been supported aiming to improve outcomes and graft 91] or increased graft failure rates [24, 78, 114] with the survival. Further developing the concept of anatomical transtibial technique. In addition to this, there are sev- ACL reconstruction, the double-bundle reconstruction eral registry studies showing higher graft revision rates has been proposed to replicate the anteromedial and with the anteromedial portal technique [111]. Some the posterolateral bundles. Several biomechanical stud- authors argued that an anatomic reconstructed ACL ies supported this technique, demonstrating improved graft is subjected to greater force than non-anatomic anteroposterior and rotational knee stability [103]. How- high placement of ACL graft [147]. Moreover, the tibial ever, this promising background resulted in a clinical tunnel-independent techniques have shown to produce a small difference in terms of joint stability [17, 28, 29, 70, higher graft bending angle than the transtibial technique 71, 86], but not in functional and subjective scores [17, Fig. 4 MRI axial (A) and sagittal (B) scans showing the case of a 24-year-old patient undergoing a previous non-anatomic ACL reconstruction with a transtibial technique (white arrow) and the new anatomic femoral tunnel placement (dotted line) using an anteromedial portal technique Costa et al. Journal of Experimental Orthopaedics (2022) 9:26 Page 8 of 14 28, 29, 71, 86, 103], as well as in terms of failure rate [17, that delaying RTS at 9 months after ACL reconstruction 28, 71, 86], since only one meta-analysis demonstrated may reduce reinjury risk by 84% [45]. Specifically, the a lower risk of graft failures with double bundle ACL reinjury rate was reduced by 51% for every month delay reconstruction [70]. for up to 9 months, beyond which no further risk reduc- More recently, there is an increasing interest in replac- tion was observed. Furthermore, some authors even sup- ing conventional round tunnels with tunnel shapes that ported delay of RTS until two years, calling into question resemble more closely the original ACL footprints. The biological and rehabilitative argumentations [97]. basic principle of these techniques comes from some However, it is obvious that time alone is not sufficient anatomic studies describing the ACL as a flat, “ribbon- for determining readiness for sports resumption [14, like” structure, with a thin, oval-shaped insertion on the 44]. Some authors proposed to focus instead on graft femur and a C-shaped tibial insertion [121, 123, 124]. maturation and functionality [33]. Histologic analysis The proposed advantages are both biomechanical with of biopsy graft specimens during second-look arthros- increased rotational stability [151], and biological due to copy is considered the gold standard to determine graft increased bone-tendon contact and decreased distance maturity [21]. Nevertheless, this method is invasive and, to the central part of the graft [152]. Despite preliminary therefore, not feasible for clinical follow-up. Magnetic promising data, clinical benefits over conventional ACL resonance imaging (MRI) may be useful for indirect reconstruction techniques have yet to be demonstrated monitoring of graft “ligamentization” process, as incom- with high-quality methodology studies. plete graft maturation is related to a hyper-intense graft In the last few years, a renewed interest in ACL repair signal on MRI [137]. However, no evident correlation was has arisen. This is not surprising because of the new par- found between signal intensity and knee stability out- adigm shift toward restoring native anatomic features come scores [137]. Therefore, a routine MRI assessment and the improved knowledge of orthobiologics. This can of graft maturity does not provide solid insights for RTS. be convenient in particular subsets of patients, such as Ideally, the information gained through MRI assessment skeletally immature patients with acute, proximal ACL should be combined with laxity measurements, to follow tears [136]. Biologically enhanced arthroscopic ACL the graft evolution and early detect potential abnormali- repair may help to improve anteroposterior knee stabil- ties (graft elongation, iterative rupture, contralateral rup- ity and patient-reported outcomes, although there is no ture, etc.). Both anteroposterior and rotatory stability is evidence of reduced rate of surgical failure [15]. However, required to safely RTS. Therefore, non-invasive devices historical reports showing unacceptable high failure rates for anteroposterior stability and pivot shift assessment at long-term follow-up [134] prevent in recommending have been developed in the last years, both to diagnose this procedure at present in patients with high functional ACL injury and to detect residual laxity after ACL recon- requests, such as athletes. struction [77, 110]. Such technologies could represent a potential aid in the follow-up evaluation of patients Return to sport undergoing ACL reconstruction and in the RTS deci- One of the greatest challenges for clinicians is to return sion algorithm. An anteroposterior side-to-side differ- the injured athlete back to sport as quickly as possible, ence < 5 mm is unanimously accepted as threshold for but at the same time not exposing the affected knee to defining a knee as sufficiently stable [33, 106]. On the excessively high reinjury risks. Unfortunately, the risk other hand, a standardized quantification of knee rota- of sustaining a second ACL injury is highest during the tory laxity is still lacking [77]. The variability of the pivot early period after return to sport (RTS), especially during shift outcome, for both displacements and accelerations, the first year after the index reconstruction [4, 118]. As a depends on how the tester is performing the maneuver result, definition of rigorous and well-coded RTS criteria itself, in terms of both the magnitudes of the applied has always been a main research focus. loads and the speed with which the limb is moved [77]. Time after ACL reconstruction is the most used cri- Furthermore, clinical studies reported knee laxity meas- terion to assess RTS readiness [14]. In a recent scoping urements at a specific time point after ACL reconstruc- review of 209 studies [118], time to RTS was reported as tion. Thus, little is known about the evolution of knee criterion in 85% of included studies and represented the laxity over the months. These conclusions are still diffi- sole criterion to give athlete the all-clear to RTS in 42% of cult to generalize, due to the diversity of such variables as studies. It goes without saying that time is a crucial varia- surgical techniques, graft types, fixations devices, associ- ble for proper graft integration and maturation [85]. His- ated injuries and measurement techniques. torically, six months for contact sports were considered Muscular strength recovery is another fundamental a good compromise [14]. Recently, this axiom has been requirement before RTS. Above all, isokinetic testing questioned. The Delaware-Oslo ACL cohort study found measures have been reported for proper evaluation of Costa et al. Journal of Experimental Orthopaedics (2022) 9:26 Page 9 of 14 quadriceps and hamstring strength [14, 138]. In addition whether PROMs may reliably predict risk of ACL rein- to this, functional and performance test have been sup- jury. Granan et al. [37] observed an increased risk of graft ported to enhance their predictive value [138]. Among failure in patients who had poor Quality of Life subscale these, hop tests have become the mainstay of perfor- of KOOS at 2 years after index ACL reconstruction. Simi- mance tests prior to returning the athlete to sport, with larly, Logerstedt et al. [76] reported that patients who the numerous variations which have been added over scored poorly on the IKDC were over four times more the years [14, 138]. Limb symmetry index (LSI) has been likely to fail the RTS tests. On the other hand, nearly widely adopted as a reliable measurement outcome. A 50% of the athletes with good scores overestimated their LSI ≥ 90% is supported before RTS [14], although some recovery [76]. authors recommended an LSI ≥ 100% for higher impact From the foregoing, it is clear that the decision to allow sports athletes [135]. However, there are some concerns RTS after ACL reconstruction solely based on one sin- regarding the use of the uninvolved limb as a reference gle criterion (time, strength recovery, functional test, for the involved limb. LSI may overestimate knee func- PROMs) cannot be adequate. An all-around evaluation tion since the resulting reduction in sports participation including biological, kinematic and psychological aspects following ACL injury leads to bilateral muscle strength is strongly recommended. Therefore, battery of tests deficits [31]. Therefore, LSI could not be specific enough including multiple measurements should be performed, to indicate the athlete has reached the preinjury level. instead of one single assessment at the hypothetical end For this purpose, some authors proposed to consider the of rehabilitative process. A stepwise evaluation process estimated pre-injury capacity (EPIC), that is obtained by during the entire rehabilitation process is thus indicated. comparing the involved-limb measures to uninvolved limb measures before ACL reconstruction [140]. Well- Conclusion sandt et al. [140] demonstrated that 90% EPIC levels This review collected and summarized a large body of were more sensitive than 90% LSI levels at assessing the research addressing the risk of ACL failure. The cur- risk of ACL re-injuries. On the other hand, the preinjury rent evidence available in literature shows that surgi- level may be not sufficient for safe sports participation cal technique represents a key factor, but this aspect and performance. Furthermore, the outcome measure alone is insufficient to ensure long-term graft survivor- of hop tests and isokinetic tests is strictly quantitative in ship. Instead, a careful preoperative evaluation is nec- nature, while outcomes related to the quality of move- essary, in order to detect any predisposing factor which ment are not captured [146]. In order to solve those may increase risk of graft failure, and therefore address issues, Padua et al. [106] proposed a clinical assessment it where possible. Similarly, the post-operative rehabilita- tool for qualitative analysis of aberrant movements dur- tion phase needs a global stepwise evaluation and should ing a standardized jump-landing test. Gokeler et al. [35] be managed by a specialized sport-traumatology team. applied this score in a cohort of 28 patients who under- Final RTS clearance decisions should positively balance went ACL reconstruction. By doing so, the authors were the athlete’s desire to savor the playing field with the risk able to detect 30% of patients with aberrant movements of graft reinjury. which may predispose to increased risk of ACL reinjury [35]. Moreover, the quality of movement is significantly Abbreviations affected by fatigue [35, 106]. Thus, repetitive testing is ACL: Anterior cruciate ligament; BMI: Body mass index; ALL: Anterolateral encouraged for proper evaluation of ACL-reconstructed ligament; LET: Lateral extra-articular tenodesis; MCL: Medial collateral liga- knee kinematics. The evolving research has made avail- ment; PLC: Posterolateral corner; LMPR: Lateral meniscus posterior root; BPTB: Bone-patellar tendon-bone; QT: Quadriceps tendon; RTS: Return to sport; MRI: able new technologies for more refined kinematics Magnetic resonance imaging; LSI: Limb symmetry index; EPIC: Estimated pre- analysis, including gait analysis, force-plates, electro- injury capacity; PROMs: Patient-reported outcome measures. myography and virtual immersive analysis [61]. How- Authors’ contributions ever preliminary findings need to be confirmed with high All authors read and approved the final manuscript. methodological quality studies. Psychological aspect is another matter that should be Funding No external funding was received for the initiation or completion of this study. considered before clear the athlete back to sport. The injury and time spent out of match can impair athletes’ Declarations motivation, that has been shown to play a key role for returning to pre-injury sport level [126]. Patient’s per- Ethics approval and consent to participate ception of symptoms, function and activity can be reli- All procedures performed in the present study were in accordance with the ethical standards of the institutional research committee and with the ably estimated with various patient-reported outcome 1964 Helsinki declaration and its later amendments or comparable ethical measures (PROMs). However, it is debated in literature standards. Costa et al. Journal of Experimental Orthopaedics (2022) 9:26 Page 10 of 14 Competing interests increases linearly as posterior tibial slope increases. Am J Sports Med One or more of the authors has declared the following potential conflict of 47(2):296–302 interest or source of funding, outside the submitted work: 12. 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