Abstract
Purpose
The purpose of this study was to evaluate the efficacy of platelet-rich plasma (PRP) in reducing femoral and tibial tunnel enlargement in patients operated on for anterior cruciate ligament reconstruction with hamstrings.
Methods
Forty male patients, in which both femoral and tibial 9-mm tunnels were performed because of the graft size, were enrolled in this prospective study. They were randomly assigned to group A (20 patients, PRP group) and group B (20 patients, control group). All patients were followed up at a median of 14.7 months (range 10–16 months), with a physical examination, the Tegner, Lysholm and objective IKDC scoring scales, and with the KT-1000 arthrometer. Moreover, they underwent a CT evaluation in order to assess the amount of tunnel enlargement.
Results
Femoral tunnel diameter increased from 9.0 ± 0.1 mm to 9.8 ± 0.3 mm in group A (p = 0.032) and from 9.0 ± 0.1 mm to 9.4 ± 0.5 mm in group B (p = 0.043). Tibial tunnel diameter increased from 9.0 ± 0.2 mm to 10.9 ± 0.2 mm in group A (p = 0.029) and from 9.1 ± 0.1 mm to 10.1 ± 0.4 mm in group B (p = 0.028). Physical examination as well as the evaluation scales used showed no differences between the two groups.
Conclusions
The use of PRP does not seem to be effective in preventing tunnel enlargement.
Level of evidence
Therapeutic study, Level II.
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Introduction
Anterior cruciate ligament (ACL) reconstruction is a widespread surgical procedure for functional instability of the knee. Among the possible complications related to this type of surgery, tibial and femoral bone tunnel widening is one of the most frequently detected and does not seem to be strictly related to the surgical technique performed or the fixation devices used [5, 13, 18, 20, 24, 25, 36, 47].
Despite the fact that this phenomenon tends to occur in the vast majority of patients, it has been shown how it does not seem to affect the long-term clinical results of the operation [2, 4, 8, 11, 17, 19, 44, 47, 53, 54].
Lately, many growth factors [6, 22, 52], such as bone morphogenetic protein-2 (BMP-2) [39], mesenchymal stem cells [45] and platelet-rich plasma (PRP) [3, 12, 14, 15, 23, 41], have been studied with the aim of promoting and accelerating graft-to-bone integration. It is reasonable to assume that a better and faster integration of the graft should reduce bone tunnel phenomenon by exposing the graft for a shorter period of time to mechanical and biological factors.
The aim of this study was to assess the effect of PRP in accelerating the graft-to-bone process and thus in reducing bone tunnel enlargement.
The hypothesis of the study is that the use of PRP would reduce the amount of bone tunnel enlargement.
Materials and methods
Forty patients affected by ACL instability were randomly assigned to group A (20 patients, ACL reconstruction with hamstrings + PRP, study group) and group B (20 patients, ACL reconstruction, control group). All patients were men, with a median age of 34.5 years (range: 18–48 years).
The presence of a chronic instability (more than 30 days from the trauma) was set as inclusion criteria to enter the study. Moreover, in order to gather an homogeneous group of patients, we only included patients who had received 9 mm intra-operative tunnel diameters, which was determined by the size of the hamstrings; furthermore, we decided to include only male patients in order to avoid bias potentially arising from lower bone density that could have been presented in female patients [16, 35, 38]. Exclusion criteria were as follows: an age higher than 50 years old, patients with associated concomitant medial or lateral collateral ligament injuries, and patients with degenerative joint disease or chondral damage detected with pre-operative standard radiographs or magnetic resonance imaging (MRI) examinations.
The PRP we used was obtained from the Immunohaematology and Transfusion Department of our hospital with the PRP Fast Biotech kit (MyCells® PPT-Platelet Preparation Tube). It was obtained by isolation and centrifugation of 10 ml of whole blood (taken about 60 min prior to surgery) in order to isolate platelets, which were infiltrated in their liquid form; furthermore, by the addition of thrombin and 10 % Ca-gluconate a few minutes before its use, a thick, adhesive gel was achieved and used as scaffold.
Surgical technique
All operations were performed by the same expert surgeon, with hamstrings, through an Out-In technique [1, 10]: in particular, the graft was fixed with the Swing-Bridge device (Citieffe, Bologna, Italy) on the femoral side and with the Evolgate (Citieffe, Bologna, Italy) on the tibial side; diameter of the Evolgate screw was 9.5 mm. In group B, the surgery was performed in a “standard” way. In group A, before passing the graft through the femoral tunnel, we added 5 ml of PRP between the peripheral part of the graft and the tunnel wall; plus, we put another 5 mL of PRP in its semisolid pattern above the graft before it was pulled down into the femoral tunnel. Similarly, on the tibial side, we added 5 ml of liquid and semisolid PRP before fixing the graft with the metallic screw.
Post-operatively, all patients started weight-bearing with the use of crutches the day after the operation. Moreover, they immediately started performing isometric exercises for muscular strength with the knee locked in a full extension brace. Two weeks after the operation, the brace was removed in all cases, and patients started active range of motion (ROM). Within the first 6 weeks, patients started progressive isotonic and isokinetic exercises. Patients involved in sports activities were allowed to return to practise their sport 6 months after surgery, and patients involved in noncontact sports after 4 months.
Follow-up
Patients were followed up at a median of 14.7 months (range 10–16 months). They were blindly evaluated by an independent orthopaedic surgeon (A.V.): range of motion and Lachman and pivot-shift tests were assessed. Moreover, they were objectively evaluated with Lysholm, Tegner and objective IKDC scoring scales, and with the KT-1000 arthrometer (MEDmetric corp., San Diego, CA, USA).
Radiological evaluation
Tunnel diameters of the operated knee were assessed with a computed tomography (CT) [27] that was performed the day after surgery and at final follow-up: a 16-slice MSCT scanner Philips MX 8000 with post-process multislab reconstruction on sagittal and coronal planes was used for the evaluation. Scanning was performed from a level just above the femoral foramen to a level right below the outer hole of the tibial tunnel. Slice thickness was 1 mm with retrorecons of 0.75 mm.
Measurements were taken at eight different levels, four each for femoral and tibial tunnels, according to what was previously described by Iorio et al. and Vadalà et al. [20, 47]. In particular, image acquisitions were obtained through a volumetric mode: a volume was scanned, and the raw data sets were manipulated afterwards, thus allowing post-process reformation along all the axes (perpendicular, horizontal and oblique).
All diameters were calculated in millimetres. All the measurements were performed by the same expert radiologist in a blinded fashion.
Statistical analysis
The data obtained from the study were analysed using the chi-square test and the Fisher exact test. The power analysis evaluation showed a 90 % power capability to detect differences between the two groups.
Results
No intra- or post-operative complications were detected in any patient of either group.
Clinical Evaluation
In Group A (study group), median Tegner value decreased from 7.7 (range 5–10) before trauma to 6.5 (range 4–10) at follow-up; mean Lysholm score was 55.4 ± 9.4 pre-operatively and 95.6 ± 5.8 after surgical procedure; the mean value of the objective IKDC form at follow-up was 92.4 ± 8.1: specifically, 16 patients (80 %) entered level A and four patients (20 %) level B; Lachman test was negative in all patients (100 %); pivot-shift test was found to be negative (grade 0) in 16 patients (80 %) and positive (grade +1) in 4 patients (20 %); and the mean anterior laxity difference between the involved knee and the contralateral healthy knee dropped from 9.5 ± 2.4 mm to 2.9 ± 1.2 mm at maximum manual handling (Table 1).
In the control group (Group B), the average score of the Tegner scale decreased from a pre-operative value of 7.1 (range 5–9) to 6.9 (range 3–9) at follow-up; the mean value of the Lysholm scale raised from 57.9 ± 5.6 to 94.1 ± 3.3. The mean value of the objective IKDC form at follow-up was 93.9 ± 6.7: sixteen patients (80 %) entered level A and 4 patients (20 %) level B; Lachman test was negative in all patients (100 %); pivot-shift test was judged as negative (grade 0) in 18 patients (90 %) and as positive (grade +1) in two patients (10 %); and the mean anterior laxity difference dropped from 10.1 ± 2.6 mm to 2.8 ± 3.1 mm at maximum manual handling.
No significant differences were detected for any of the parameters assessed between the two groups (Table 1).
Radiological results
Femoral tunnel diameter increased from 9.0 ± 0.1 mm to 9.8 ± 0.3 mm in group A (p = 0.032) and from 9.0 ± 0.1 mm to 9.4 ± 0.5 mm in group B (p = 0.043) (Fig. 1). Tibial tunnel diameter increased from 9.0 ± 0.2 mm to 10.9 ± 0.2 mm in group A (p = 0.029) and from 9.0 ± 0.1 mm to 10.1 ± 0.4 mm in group B (n.s.) (Fig. 2). Even though a statistical difference was always found comparing pre- and post-operative bone tunnel diameters for femoral and tibial tunnels in all patients of both groups, comparison of final values between the two groups never showed statistically significant differences (Table 2).
Discussion
The most important finding of the present study was the inefficacy of the PRP in accelerating the graft-to-bone integration process and consequently in decreasing the tunnel enlargement phenomenon.
It has been widely shown how the ligament autograft maturation process goes through various stages [29, 50, 51] and how growth factors are present in each of these stages [32, 50, 51]. Orrego et al. [36] have shown good results from the use of PRP in accelerating and improving bone-tendon integration. However, the vast majority of such types of studies so far published were conducted in vitro or in animals [28, 30, 31, 33, 37, 49, 52]. The use of growth factors in humans has still not been adequately investigated, and results shown by authors in the last years are discordant [23, 34, 42, 46]. De Vos et al. [7] obtained the same results in pain and activity improvement compared with a saline injection in the treatment of Achilles tendinopathy, while Kon et al. [19], in treating patellar disorders, showed marked improvement in knee function and quality of life, stating also that PRP has to be associated with physiotherapy in order to obtain better outcomes.
ACL reconstruction is obviously one of the orthopaedic surgical fields in which the use of any type of growth factors would be useful, since the integration process of the reconstructed ACL is one of the keys for a successful long-term follow-up outcome. In this paper, we aimed to assess whether the use of PRP would have accelerated the bone-tendon integration process by evaluating the bone tunnel enlargement that is strictly related to the integration process itself. Indeed, both mechanical and biological factors [2, 8, 17, 19, 43, 44, 47, 53, 54], which are thought to work in sync in determining the widening phenomenon, play a role in the mismatch between the peripheral part of the tendon and the tunnel wall. Indeed, both the bungee [21] and the windshield wiper phenomena [9] (among mechanical factors) and the synovial bathing effect [48] (among biological factors) take place until this area fills up with Sharpey’s fibres and the ACL is fully incorporated within the bone tunnels.
As a consequence, a faster and better integration process should lead to a lower amount of femoral and tibial enlargement, because of the minor time in which these factors might have their effects. We hypothesized that a faster integration process due to the use of PRP would have significantly reduced the bungee and windshield wiper effects, thus avoiding a significant tunnel enlargement phenomenon.
Previous studies [5, 20, 24, 40] have already reported how different fixation devices might influence the amount of tunnel enlargement, probably because of the different capabilities of such constructs to minimize mechanical and biological factors. Similarly, Vadalà et al. [48] showed how different rehabilitation protocols significantly influence the tunnel widening process.
As a matter of fact, results of our study do not support the use of PRP in reducing bone tunnel enlargement: indeed, comparison of radiological data of the two groups shows similar values of tunnel widening both on the femoral (9.8 mm in group A vs. 9.4 mm in group B; n.s.) and on the tibial side (10.9 mm in group A vs. 10.1 mm in group B; n.s.). Similarly, the clinical examination and the scoring scales used showed no differences either.
Limitations of this study are certainly the small size of the groups and the lack of a histological analysis. Regarding the small size of the groups, we tried to gather the most homogeneous types of patients possible, in order to avoid bias due to associated pathologies. In the same way, a histological analysis would have provided more scientific data of how PRP really would act in the mismatch between the graft and bone tunnel [26]. Moreover, another important limitation of this study is the limited power of the study due to the small size of the groups considered.
As a matter of fact, the use of PRP did not provide any effect in reducing the amount of tunnel enlargement. The initial hypothesis that PRP would have avoided this phenomenon was not confirmed.
Conclusion
The use of PRP does not seem to be effective in preventing, or even reducing, femoral and tibial tunnel enlargement in patients operated on for ACL reconstruction with hamstrings.
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Vadalà, A., Iorio, R., De Carli, A. et al. Platelet-rich plasma: does it help reduce tunnel widening after ACL reconstruction?. Knee Surg Sports Traumatol Arthrosc 21, 824–829 (2013). https://doi.org/10.1007/s00167-012-1980-z
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DOI: https://doi.org/10.1007/s00167-012-1980-z