A Review of Rehabilitation Protocols Following ACL Reconstruction

An anterior cruciate ligament (ACL) injury is a major injury for any individual (13). The ACL is one of the four ligaments that provide stability to the knee. This ligament is located in the center of the knee and helps control forward and rotational movement of the tibia (2). The ACL is the most commonly injured ligament in the body, for which surgery is frequently performed. It is estimated that 175,000 ACLRs were performed in the year 2000 in the United States at a cost of more than $2 billion. This number continues to increase. Incidence rates for tears are difficult to assess because some injuries remain undiagnosed. The majority of ACL tears (67% in men and almost 90% in women) occurred without physical contact (2). The mechanism of injury for an ACL injury is an acceleration or deceleration twisting injury to the knee and the individual typically hears a pop (2, 48, 13). A Lachman’s test is a reliable test that is generally used to conclude whether the individual has torn their ACL (48).

An athlete who sustains an ACL rupture has few options for treatment. If they wish to continue to compete at the pre-injury level, then the only viable option is to undergo an ACLR. Otherwise, the athlete is at a substantial risk of sustaining subsequent degenerative changes in the knee at a young age (40). Rehabilitation programs are designed to rebuild muscle strength, reestablish joint mobility and neuromuscular control, and to enable patients to return to pre-injury activity levels (3). These objectives are based on the knowledge of patients undergoing ACLR (3, 24, 52). Interventions could therefore include stem cell therapy, closed and opened chain exercises, glucosamine and creatine supplementation, cryotherapy, rehabilitative bracing, traditional versus accelerated rehabilitation, and DIS. There are various surgical techniques employed in the ACLR repair through the patellar defect, arthroscopically assisted techniques, and the mini-arthrotomy technique. A major emphasis is now placed on the preoperative and postoperative rehabilitation with an ACLR. An accelerated and aggressive program which relies on early return and maintenance of full hyperextension equal to the contralateral knee, early weight bearing, and closed chain exercises is recommended (40).

Although there have been attempts to examine the effect of these interventions following ACLR, the systematic reviews have been out dated and do not examine modern rehabilitation techniques. For example, two systematic reviews regarding ACLR rehabilitation (3, 36) reviewed studies published prior to 1990. Studies published prior to 1990 contained quality issues that were not yet recognized. This systematic review chose most of the reviewed studies from those published after 2000. This review also investigated modern rehabilitation procedures such as DIS and stem cell therapy, which other related systematic reviews failed to mention (3, 36).

Of particular interest to this study was to investigate the most effective rehabilitation method for returning the injured individual back to physical activity as quickly and efficiently as possible. The goal of this systematic review was to collect the available randomized controlled trials (RCTs) in ACL rehabilitation to assist in the development of rehabilitation methods. Therefore, the primary question of this review was What is the ideal rehabilitation program for postoperative ACLR? i.e., what combination of treatment is the most effective for returning an individual recovering from ACLR back to pre-injured activity?

Methodology

Selection of Trials

To determine whether a trial should be included, trials were reviewed using predetermined criteria. The trial had to be a randomized controlled trial and the patient needed to have ACLR surgery. The study was also required to involve rehabilitation methods and protocols following ACLR surgery. Exclusion criteria included studies not pertaining to ACLR rehabilitation, studies involving predisposing conditions, or preventative measures for ACL injuries.

The methodological quality of the studies was assessed based on the method of randomization, power analysis, assessor and participant binding, number of subjects, length of follow-up and sufficiency of the follow-up, and a thorough description of the rehabilitation interventions. Some studies failed to establish an effect because the exercises are ineffective, the time, duration, specificity, or intensity of the exercises/program is not sufficient for provoking a response. The patients may have also not been compliant with the rehabilitation treatment. Furthermore, RCTs from the literature reviewed covered the following areas of ACL rehabilitation: stem cell therapy, closed and opened chain exercises, glucosamine and creatine supplementation, cryotherapy, rehabilitative bracing, traditional versus accelerated rehabilitation, and DIS.

Database and Search Strategy

Papers were identified from the following sources: MEDLINE (2000 to 2015), PubMed (1990to 2015), and Google-scholar (2000 to 2015). Searches from each database included the search terms “anterior cruciate ligament,” “rehabilitation,” and “randomized controlled trial.” These searches revealed 299 studies. Of these 299 papers, 273 were excluded because they failed to meet the inclusion criteria for assessment. This left 26 studies to be included from PubMed, MEDLINE, and Google-scholar in this systematic review (see Table 1).

Results

Stem Cell Therapy

Stem cell therapy has been shown to have promising prospects and draws increasing attention (19). Despite the significant amount of discussion that has occurred regarding the quality and effectiveness of stem cell therapy following ACLR surgery, few studies have been published that have investigated this issue (19, 43). Hirzinger et al. (2014) evaluated the biological factors that influence the healing process. The factors discussed included local intraligamentous cytokines and mainly cell repair mechanisms that are controlled by stem cells or progenitor cells. This studied concluded that there is an unclear deduction whether trophic factors deriving from stem cells improve the regeneration or if the cells themselves form new tissue. Silva et al. (2012) carried out a study focusing on the graft-to-bone healing in ACLR. Patients received intra-operative infiltration of their graft with non-cultivated adult bone marrow-derived stem cells. MRI evaluation showed no difference between the treatment and the control group (43). Hao et al. (2016) investigated bone marrow-derived mesenchymal stem cells to emerging ACL-derived CD34+ stem cells. This study suggests that these stem cell types have been proven to be effective in accelerating tendon-bone healing (19).

In spite of the high hopes pinned on cell therapy approaches not only in ACL repair but in musculoskeletal regeneration in general, the use of stem cells is still far from reaching everyday clinical practice (23). Besides regulatory obstacles, there needs to be a concise conclusion on which cell type is most beneficial for regenerating ligament tissue.

Closed and Open Chain Exercises

Resistance training using open kinetic chain (OKC) exercises for patients recovering from ACLR surgery has lost favor mainly because of research indicating that OKC exercises cause greater ACL strain than closed kinetic chain exercises (CKC) (10). Bynum et al. (1995) evaluated rehabilitation following bone-tendon-bone auto graft ACLR using open versus closed chain exercises. Twenty-one patients in the closed chain group felt they returned to normal activities of daily living sooner than expected versus 10 patients in the open chain group. The results of this study suggested that CKC are safe and effective and offer a variety of advantages of less stress on the healing graft. These patients also experienced less patella-femoral pain.

Morrisey et al. (2000) sought to investigate knee extensor resistance training using OKC and CKC exercises for patients recovering from ACLR surgery. This study measured knee laxity for both types of rehabilitation programs and concluded that the use of OKC exercise compared to CKC exercise led to an increase in knee looseness post-training. Hopper at al. (2001) also studied the effect of OKC and CKC exercises. The rehabilitation methods used involved level walking for the OKC group and leg presses for the CKC group.

Contrasting to the results presented in the Bynum et al. (1995) study, Mikkelsen et al. (2000) emphasized the addition of OKC exercises to a CKC rehabilitation program. This study investigated knee laxity, thigh muscle torque, and return to pre-injury sports level. The researchers concluded that the addition of OKC quadriceps training after ACLR results in a significantly better improvement in quadriceps torque without reducing knee joint stability at 6 months. The researchers also found that athletes involved in the OKC rehabilitation program returned to their previous activity earlier.

The literature established the need for a more extensive research investigation in this area. In the Bynum et al. (1995) study there was no concise determination for the specific exercise that may have led to the increase in knee laxity. Mikkelsen et al. (2000) did not discuss genetic predisposition factors that could have led to a faster recovery time to their previous activity. The studies presented also assessed the final outcome in a short period of 6-weeks. This follow-up may be too short to make any clear deductions (8, 9, 10).

Glucosamine and Creatine

Creatine supplementation has been shown to augment training-induced strength gains (49). Tyler et al. (2004) proposed that creatine supplementation will facilitate strength gains following ACLR and promote healing. Isokinetic testing was used to measure quadriceps and hamstring strength, while hip flexor, abductor and adductor strength was measured using a dynamometer. Hop tests also assessed the knee strength of each patient. Over the course of the 6 month study, the researchers revealed that creatine supplementation did not affect the strength improvements made by the subjects (49).

Other supplementation rehabilitation methods studied involved the investigation of glucosamine supplementation following ACLR (15). Eraslan et al. (2015) administered glucosamine-sulfate to half of the sample size while providing a placebo to the rest of the subjects. After evaluating knee pain and function while also using isokinetic testing, the researchers revealed significant improvements in both groups after the eight week study. However, there was no significant rehabilitation differences detected when athletes used glucosamine supplementation during rehabilitation.

Creatine supplementation does have the efficacy to increase strength gains, however studies have shown that this type of supplementation is not effective for patients rehabilitating from ACLR surgery. Further research could investigate the supplementation of creatine during CKC and OKC rehabilitation programs which have shown mixed findings in regarding recovery time following ACLR. Regarding glucosamine supplementation, Eraslan et al. (2015) was the first study regarding this topic. Further studies with a longer rehabilitation program will help obtain clear evidence regarding the efficacy of glucosamine supplementation on ACLR rehabilitation. From the presented studies, it may be viable to conclude that it is not necessary to include creatine or glucosamine supplementation in the rehabilitation regimen for patients recovering from ACLR surgery (15, 49).

Cryotherapy

Unrelieved postoperative pain may impair rehabilitation, compromise functional outcomes, and lead to patient dissatisfaction (25). Cryotherapy is a popular therapeutic modality to improve the outcomes following surgery. Studies have investigated the use of this therapeutic technique to reduce pain for patients recovering from ACLR surgery (25). Koyonos et al. (2014) studied two separate groups in which one group received no cryotherapy while the second group underwent 30-90 minutes cryotherapy. This studied employed the use of self-report measurements to assess the subject’s perceived pain. Barber et al. (1998) also implemented a similar experimental design by evaluating two separated groups.

There have been similar findings in studies which have investigated the implementation of cryotherapy treatment in the rehabilitation of patients following ACLR surgery (4, 5). Barber et al. (1998) concluded that cryotherapy is safe and effective treatment for reducing post-operative pain. Additional research has also identified the efficacy of the implementation of cryotherapy in the rehabilitation regimen for ACLR surgery patients (4, 5).

While previous research has displayed significant findings regarding the use of cryotherapy, additional research with a different experimental design is necessary for a clear conclusion. These studies had patients self-report their pain perceptions to conclude that cryotherapy will lead to less medication required for pain management. Self-report techniques can lead to bias and unreliable data which is why other experimental techniques should be used to assess the efficacy of cryotherapy (51).

Neuromuscular Training

The biomechanics of the knee are altered after an ACL injury. Rehabilitation protocols that only focus on restoring mechanical restraints has been shown to be insufficient for a pleasing outcome (45). Neuromuscular training may induce alterations in muscle activity patterns to enhance the control of abnormal joint translations during functional activities (52). Three RCTs were reviewed which examined the evidence of using neuromuscular training programs during the course of postoperative ACLR rehabilitation (27, 36, 42).

Liu-Ambrose et al. (2003) investigated subjects undergoing a strength rehabilitation program compared to subjects in a neuromuscular training program. The neuromuscular training group demonstrated a greater percent change in isokinetic torques than the strength group. Fitzgerald et al. (2003) was an RCT which evaluated patients exposed to neuromuscular training with rehabilitation. In this study, subjects were evaluated by the performance of isokinetic quadriceps exercise throughout a 16 week span. Upon conclusion of this study, there was an increase in the activities of daily living in the neuromuscular training group, but there were no significant differences in pain perception (16). Ross et al. (2001) also examined neuromuscular training in conjunction with CKC exercises. The researchers found significant evidence that the addition of neuromuscular training produced better lower extremity performance compared to the control group (35). However, this study did not feature blinding or independent assessment of subjects.

Due to the various constraints used in these studies, it is difficult to make a generalized conclusion regarding the use of neuromuscular electrical stimulation following ACLR. The majority of these studies did not assess randomization, and some were not blinded (35, 36, 42).Not blinding the study could lead to bias data and cause the research to be unreliable. Also, baseline data were only reported in one study (16). While some studies demonstrated improved isokinetic strength, this was not connected with patient based outcomes or other testing related to knee function. Also, patient satisfaction and pain management was seldom addressed. Neuromuscular electrical stimulation has the potential to improve quadriceps strength and could facilitate the rehabilitation process following ACLR. However, there have not been studies which have proven that this treatment should be required for ACLR rehabilitation.

Rehabilitative Bracing

Given the growing appreciation for restoring native ACL anatomy and both biochemical and neurosensory function, current surgical innovations suggest strong potential for achieving a closer fusion between surgical repair with possible use of internal bracing (31). Internal bracing also provides an additional option for repairing adjacent knee tissues that function in synchrony with the ACL such as the medial collateral and anterolateral ligaments (123). The evidence base supporting post-surgical knee brace use tends to decrease across the healing continuum following ACLR surgery. The traditional focus on postsurgical knee joint protection must be balanced with concerns related to the potential for knee brace-induced maladaptive lower extremity kinematic compensations and range of motion (ROM) restrictions (#). Knee brace use needs to between match patient needs at each phase of the return to sports process (31). Studies have suggested that even following knee brace prescription, safe training without brace use is essential to better simulate the loads needed for tissue healing, collagen deposition and remodeling (31). Over time the rehabilitation team would need to have a planned strategy to gradually lead the patient away from the use of a brace once biomechanical tissue integrity and high-level performance function have been reestablished (31).

Contrast to the opinions states in the previously mentioned literature, one systematic review (26) found strong evidence that demonstrated the ineffectiveness of postoperative bracing. Two RCTs in this review suggested that bracing did not protect against postoperative injury, decrease pain, alter range of knee motion, or improve knee stability (20, 22).

Hiemstra et al. (2009) performed a RCT comparing knee immobilization with no bracing following ACLR with hamstring tendon; early pain was assessed in 88 patients. The primary outcome was patient pain self-assessed at two days after surgery, as well as analgesic use, knee motion and effusion, and wound-healing throughout the first 14 days after ACLR. There were no differences in pain, analgesic use, ROM, or effusion at 2 or 14 days. Harilainen & Sandelin (2006), assessed knee laxity and isokinetic strength in a brace group, compared to a group who was given no bracing post-ACLR. There were no observed differences between the two groups. The majority of the literature reviewed suggests that bracing following ACLR remains neither necessary nor beneficial and adds to the cost of the procedure (20, 22, 26).

Traditional Versus Accelerated Treatment

Because of the controversy surrounding accelerated ACL rehabilitation, studies have investigated the retrospective comparison of traditional rehabilitation versus an accelerated approach (12). De Carlo et al. (1992) demonstrated that patients who started weight bearing or gained ROM earlier than advised had stronger, more functional knees at the completion of rehabilitation. In a second RCT, a dramatic decrease was observed in the number of scar resections and surgical manipulations required to achieve full ROM once the current rehabilitation program was initiated (39).

Patients undergoing ACL reconstruction achieved a better result with the current accelerated rehabilitation program than they did under the initial protocol in De Carlo et al. (1992). By encouraging early passive terminal extension, early weight bearing, and quadriceps control while emphasizing closed kinetic strengthening exercises, the patients were able to progress through the postoperative rehabilitation period at an accelerated pace. The patients were able to gain full ROM by 6-8 weeks, full quadriceps strength was regained at an earlier time without compromising stability, and return to competition occurred as early as 4-6 months following surgery. In another report from Shelbourn & Nitz (1990), it was demonstrated that an accelerated rehabilitation program after ACLR can be beneficial. This report indicated that in one surgeon’s practice, the accelerated program was more effective than a traditional program in reducing limitations of motion and loss of strength while maintaining stability and preventing anterior knee pain (37).

Limitations of these studies indicated that these improvements can be generalized to patients form more than one surgeon. Although improved range of motion and strength were observed, the patients had received surgical care by three different physicians. This study prompts suggestions for further research such as a comparison between surgeons to determine if a particular surgeon had superior results. Also, an additional study could be implemented with a follow-up period longer than 1-year (37, 38, 39, 40, 41).

Dynamic Intraligamentary Stabilization

Recently, a new technique called dynamic intraligamentary stabilization (DIS) was introduced for the acute repair of ACL ruptures (7). Buchler et al. (2016) reported the functional recovery for patients undergoing ACLR rehabilitation alongside DIS. This strategy preserved the torn ACL and is a fairly new rehabilitation method implemented in the patient’s treatment regimen. The DIS method involves employing an internal stabilizer to keep the unstable knee in a posterior translation, combined with micro-fracturing and platelet-rich fibrin induction at the rupture site to promote self-healing. Eggli et al. (2016) used a postoperative clinical outcome method with the utilization of a patient satisfaction score. The researchers also assessed knee laxity at, 3, 6, 12, 24 and 60months. Based on the instruments’ outcome scores a combined success definition was applied. The patients’ preoperative scores were assessed as early as possible (14).

Research has indicated that DIS technique with proper rehabilitation following ACLR provides successful functional recovery and low re-rupture rate at one year-follow up. In one of the DIS studies (7) only 3 out of the 45 patients suffered from re-rupture during the first 12 postoperative months. Other research regarding DIS rehabilitation treatment has shown a 5-year survival rate of 80 %, and all patients with a functionally healed ACL displayed excellent outcomes and satisfaction with regards to the treatment result (14). Although DIS research has produced significant findings, the small sample sizes used and the lack of a control group are the major drawbacks from the presented analyses (reference #). Therefore, a representative failure rate cannot be concluded from the small case series (14). Research published by Kosters et al. (2015) confirmed these findings.

Discussion

This systematic review provides evidence that certain rehabilitation methods for patients recovering from ACLR surgery may have the efficacy to decrease pain, promote healing, and lead to a faster rate of recovery for the injured individual. Many issues relating to ACLR rehabilitation have been evaluated using randomized controlled trials. However, the quality of the reviewed studies is variegated. Most of the research reviewed contains a form of potential bias. Despite this bias, reasonable conclusions can be generated from the research used in this systematic review. An accelerated rehabilitation protocol appears beneficial within the 5-6 month time frame, and has the efficacy to facilitate the recovery process of an ACLR surgery. Also, CKC rehabilitation within the first 6 weeks post-surgery might allow for better patellar tracking with minimal stress on the ACL and can help maintain good joint congruency. Early weight-bearing may also be beneficial for decreasing patellofemoral pain.

From the information gathered by this systematic review, an ideal rehabilitation regimen for the injured individual should involve an early intervention strategy focused on restoring ROM, muscle strength, and ligament stability with the utilization of CKC exercises. DIS could also be implemented in the rehabilitation protocol within the first three months after surgery. The patient should also undergo at least 30-90 minutes of cryotherapy immediately following ACLR.

Despite the extensive review of 26 randomized controlled trials, there is still significant doubt regarding most of the rehabilitation methods suggested. Further studies are necessary to continue to add confidence to the ACLR rehabilitation procedures. There is a need for further research involving good quality, large scale randomized trials with sufficiently long follow-up to fully assess knee function and recovery. Future research should also consider the timing of rehabilitation as well as supplemental rehabilitation exercises to continue to improve the quality of care delivered to patients following ACLR.

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Table 1. Chronological list of randomized control trials (RCT) based on the search criteria given for this study: from PubMed, MEDLINE, and Google-scholar

Authors	Intervention (Group 1)	Intervention (Group 2, 3, or 4)	N	Testing and follow-up time	Outcome measurements	Results
Barber et al. (1998)	Cryotherapy	Standard Rehabilitation	100	1-week	Group 1 experienced less pain	Cryotherapy is safe and effective treatment for reducing post-operative pain
Beck et al. (2004)	Cryotherapy	Standard Rehabilitation	25	30-90 minutes of testing F/U time N/A	Group A had important absolute and perceptual improvement when compared to Group B regarding measures of pain and knee flexion/extension ROM	Cryotherapy in the immediate postoperative period of ACLR was effective to improve pain and ROM of the knee
Büchler et al. (2016)	DIS	Standard Rehabilitation	45	12 months	Good functional recovery following ACLR, most patients experienced no pain and had significant results on hop tests	DIS technique with proper rehabilitation provides successful functional recovery and low rerupture rate at one year F/U
Beynnon et al. (2005)	Accelerated Rehabilitation	Standard Non-accelerated Rehabilitation	25	24 months	No difference in the increase of anterior knee laxity, groups were similar in satisfaction, activity, and function	ACLR followed by either accelerated or non-accelerated rehabilitation produces the same increase of anterior knee laxity
Bynum et al. (1995)	CKC exercise rehabilitation	OKC exercise rehabilitation	18	N/A	High recorded peak quadriceps activity during loaded, 2-legged, CKC exercises	CKC exercises may be effective treatment for protecting the ACL following surgery
De Carlo et al. (1992)	Accelerated Rehabilitation	Standard Non-accelerated Rehabilitation	1,508	12 months	The accelerated group achieved higher average hyperextension and flexion values than the control group	Patients undergoing ACLR achieved a better result with an accelerated rehabilitation program
Eggli et al. (2016)	DIS	Standard Rehabilitation	10	5 years	DIS Group experienced a 5-year survival rate of 80% and showed excellent outcomes and satisfaction with regards to treatment	DIS treatment can significantly increase patient satisfaction and recovery following ACLR
Eraslan et al. (2015)	Glucosamine Supplementation	Placebo Group	30	8 weeks	Both groups experienced significant improvements in isokinetic testing	Glucosamine supplementation did not improve the rehabilitation outcomes of athletes after ACLR
Fitzgerald et al. (2003)	NMES	Standard Rehabilitation	43	12 and 16 weeks	The NMES group demonstrated moderately greater quadriceps strength at 12 weeks and moderately higher levels of self-reported knee function at both 12 and 16 weeks	The modified NMES quadriceps training protocol can be a useful adjunct to ACLR rehabilitation programs, but the treatment effect is smaller than what has been reported in previous studies.
Frobell et al. (2010)	Accelerated Early Rehabilitation	Standard Rehabilitation	121	2 years	Absolute change in mean KOOS4 score was similar in both groups	A strategy of rehabilitation plus early ACLR was not superior to a strategy of rehabilitation plus delayed ACLR
Henle et al. (2015)	DIS	Standard Rehabilitation	278	24 months	After DIS treatment the mean IKDC, Lysholm, and Tegner scores were 93.6, 96.2, and 4.9 points respectively. Patients also reported high satisfaction	Anatomical repositioning along with DIS leads to clinically stable healing of the torn ACL
Koyonos et al. (2014)	Standard Rehabilitation	Cryotherapy	53	First 36 hours following ACLR	Group 2 patients reported less pain and used less narcotic use for the first 36 hours than Group 1	Cryotherapy is a safe and effective multimodal pain regimen for patients undergoing ACLR
Kosters et al. (2015)	DIS	Standard Therapy	55	12 months	Satisfying values for the Lysholm, Tegner and International Knee Documentation Committee outcome scores. High patient satisfaction. Mean anterior translation difference on Lachman test of 1.7 mm	DIS can provide biochemical and biological conditions for self-healing of the ACL
Liu-Ambrose et al. (2003)	Proprioceptive training	Isotonic strength training	10	12 weeks for strength training 6.7 weeks for proprioceptive training	Enhanced peak torque time hamstring concentric and eccentric hamstring and quadriceps torque in both groups	Both training protocols influenced peak torque time
Hiemstra et al.	Knee immobilization after 14 days	No immobilization	88	2 Weeks	Analgesic use, self-reported pain, ROM, wound-healing was equal between each group	No difference in pain or medication use after 14 days
Harilainen & Sandelin	Brace for 2 weeks	No brace	60	2 Weeks with a 5 year F/U	No difference in knee laxity, or isokinetic strength	Bracing does not appear to effect knee laxity or isokinetic strength for ACLR patients in the postoperative phase
Morrissey et al. (2000)	OKC strength training	CKC strength training	43	6 weeks	No differences in knee joint laxity were experienced between each group in the Knee Signature System Arthrometer	A rehabilitation program focusing on either OKC or CKC strength training does not appear to influence knee joint laxity
Mikkelsen et al. (2000)	CKC strength training	CKC and OKC strength training	44	31 months	No significant differences in knee laxity. Patients in group 2 increased their quadriceps torque, but no differences in hamstring torque were found between both groups. Patients in group 2 returned to activity faster than group 1	The addition of OKC quadriceps strength training after ACLR results in a significantly better improvement in quadriceps torque without reducing knee joint stability
Muaidi et al. (2009)	Patients with ACLR	Healthy control group with no ACLR	30	3 months and 6 months	A deficit was found in preoperative knee rotation proprioception compared with health controls	Knee rotation proprioception is reduced in ACL-deficient participants compared with healthy controls
Palm et al. (2012)	Injured legs with or without a knee brace	Uninjured legs with or without a knee brace	58	N/A	Overall stability index scores were 3.0 for uninjured legs when unbraced, 2.8 for uninjured legs when braced,	Elastic knee braces increase postural stability in patients with ACL rupture. There was no difference in postural stability between uninjured and injured legs while braced
Shelbourne et al. (1990)	All subjects were treated with early motion with emphasis on full extension	N/A	155	2 – 7 years	Lachman test and Cybex test showed 98% and 90% mean hamstring and quadriceps strength respectively. High mean scores on pain and activity level scales	ACLR rehabilitation with emphasis on early full extension postoperatively achieved excellent results and provided a stable knee
Snyder-Mackler et al. (1995)	High intensity NMES+CKC exercises	Group 2- High level volitional exercises + CKC exercise Group 3- High and low intensity NMES+CKC exercises Group 4- Low intensity NMES+CKC exercises	110	4 weeks	70% increase in quadriceps strength in Groups 1 and 3 51% increase in quadriceps strength in Group 4	Neuromuscular electrical stimulation has the potential to improve quadriceps strength and could facilitate the rehabilitation process following ACLR.
Silva et al. (2012)	Group with non-cultivated bone marrow stem cells	Group without non-cultivated bone marrow stem cells	43	3 months	There was no difference in the signal-to-noise ratio of the interzone on MRI between the two groups	Adult non-cultivated bone marrow stem cells do not seem to accelerate graft-to-bone healing in ACLR
Tagesson et al (2008)	Supplemental OKC exercise group	Supplemental CKC exercise group	42	14	Greater increase in isokinetic quadriceps strength in OKC exercise group and similar tibial translation for both groups	OKC exercise does not appear to have an adverse effect on knee joint stability in ACLR patients. OKC quadriceps strengthening exercises should be included in a rehabilitation program for ACLR patients
Tyler, T.F. (2004)	Creatine Supplementation	Placebo Group	60	12 weeks	Significant increases in strength on the involved side of knee extension, knee flexion, hip flexion, hip abduction, hip adduction in both groups	Patients do not benefit from creatine supplementation during the first 12 weeks of ACLR rehabilitation
Wojtys et al. (2000)	Neuromuscular functioning	Control Group with no knee abnormalities	65	1.5 years	Muscle function in most subjects had not returned to normal, declines in muscle performance persisted in most patients	There were no differences in neuromuscular functioning between the ACLR group and the control group

NMES, neuromuscular electrical stimulation; ROM, range of motion; ACLR, anterior cruciate ligament reconstruction; F/U, follow up; DIS, dynamic intraligamentary stabilization; CKC, closed kinetic chain