Graft selection in ACL reconstructive surgery: past, present, and future ...

R E V I E W A R T I C L E

Graft selection in ACL reconstructive surgery: past, present, and future Ahmad Oryan, Ali Moshiri and Abdolhamid Meimandi-Parizi

ABSTRACT Anterior cruciate ligament (ACL) tear is a frequent orthopaedic injury. ACL reconstruction, both in humans and animals, is more developed than in past decades. Many experimental and clinical trial studies have been performed, using various grafts with several different techniques, aiming to improve ACL reconstruction. However, there is still a large gap between the present treatment modalities and the final outcome in patients who have had ACL reconstructive surgery. The autograft bonepatellar tendon-bone complex and hamstring tendon grafts are the gold standard graft types for ACL reconstruction. This review introduces graft options and discusses advantages, disadvantages, and outcomes. Bone tunnel healing, strategies to enhance the bone tunnel healing, and the future of ACL reconstruction also are briefly described. Key Words anterior cruciate ligament, patellar tendon, hamstring tendon, bone tunnel healing, graft selection

have been suggested for those who are engaged in reconstructive surgical research.

GRAFT SELECTION IN ACL RECONSTRUCTION Different types of grafts have been used to reconstruct the torn ACL. Generally, these can be divided into autogenous, allogenous, and xenogenous grafts based on the species of the donor. Tissue-engineered grafts are the fourth new type that can be made up of any of the previously mentioned grafts, from synthetic products or their combinations.9,10 Tissueengineered grafts overlap with the xenografts but possess more options and can be divided into three categories, including biologic, synthetic, or hybrid grafts, based on the origin of their material.10 The advantages and disadvantages of each graft type are briefly highlighted in Table 1.

AUTOGRAFTS INTRODUCTION

O

ver the past 10 years, anterior cruciate ligament (ACL) reconstructive surgery has improved.1--4 The procedure usually is carried out arthroscopically using different types of grafts.1,5,6 Despite the popularity of the procedure, the preferred graft remains controversial. Ideally, the graft should have similar characteristics as the native ACL, be incorporated in the tibial and femoral tunnels with proper fixation characteristics, heal fast and maintain its viscoelastic characteristics for a long time with minimal adverse effects on the extensor mechanism, without pain or osteoarthrosis.7--9 This paper discusses different types of grafts, their characteristics, and their outcomes in human ACL reconstructive surgery. Because of insufficient healing potential in the bone tunnel or abrasion of the graft at the tunnel exit, all types of ACL reconstruction have a proportion of graft failure. Therefore, bone tunnel healing and strategies to improve healing potential are discussed in this paper. The new areas of research in ACL reconstructive surgery also School of Veterinary Medicine, Shiraz University, Shiraz, Iran Financial Disclosure: The authors report no conflicts of interest. Correspondence to Ali Moshiri, DVM, DVSc, Division of Surgery and Radiology, Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Fars, Iran Tel: þ 989123409835; þ 982188002991; fax: þ 987116138662; e-mail: [email protected] 1940-7041 r 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins

Volume 24 Number 3 May/June 2013

Intraarticular reconstruction of the ACL can be done using many types of autogenus grafts, such as combined semitendinosus gracilis hamstring tendon, bone-patellar tendon-bone composites, or quadriceps tendon.27 However, most surgeons prefer the central third of the patellar ligament; others use one or two strands of hamstring tendon.11 Recently, four strands were found to be superior to two strands.2 The advantages of autografts compared with allografts have been demonstrated.11 For example, they are not involved in transmission of diseases, do not initiate host’s immune reaction, and are inexpensive.11 However, serious limitations have been suggested for autografts, such as limited availability, increased operative time, and adverse functional changes, including muscle weakness at the donor site and graft site morbidity, which may have a detrimental effect on the final outcome of the surgical reconstruction.12

ALLOGRAFTS The clinical data of both humans and animals have suggested that, as with autograft tissues, the allograft tissue revascularizes and becomes viable after implantation.12,13,22 However, the rate of graft incorporation and remodeling are slower for allograft than for autograft.12 Clinical studies with 5-year and 7-year follow-up have demonstrated that the outcomes of early ACL allograft reconstructions are similar to those of the autografts.10,28 The incidence of chronic knee effusion after allograft reconstruction diminishes. This is perhaps because of the improved allograft procurement and Current Orthopaedic Practice

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TABLE 1. Advantages and disadvantages of application of autografts, allografts, artificial, or xenografts in ACL reconstruction. Graft type Autograft Origin

Allograft

Artificial or xenografts

Origin

Combined semitendinosus gracilis hamstring tendons Bone-patellar tendon-bone composites Quadriceps tendon Advantages

Disadvantages

1. They are not involved in transmission of diseases11 2. Do not initiate host’s immune reaction11,12 3. Inexpensive11,13 4. Do not need special instrument for preservation of the harvested graft14,15 5. Fewer ethical concerns16 6. Healing is faster8 7. Long-term viability of the graft9,17,18

1. Limited availability12 2. Increased operative time12 3. Adverse functional changes (eg., muscle weakness at the donor site)1,9 4. Donor site morbidity 8,12,16,19

Origin

Bone-patellar tendon-bone composites Achilles’ tendon Anterior tibialis Fascia lata Hamstring Advantages Disadvantages 1. No donor site morbidity 19 2. Decreased operative time20 3. Better cosmetic appearance than autografts17,21 4. No functional impairment12,22,23

1. Limitation of their supply 2. High cost 3. Disease transmission (e.g., HIV or hepatitis)14,20 4. Their longterm viability is not clear1,18 5. Immune response and rejection may occur12,22--24 6. Ethical concerns 7. Healing concerns

Calf skin (natural [N]) Bovine or equine Achilles tendon (N) Submocusa of the calf small Intestine (N) Synthetic (eg., PDS, PLGA, vicryl, nylon) Hybridized (natural þ synthetic) Advantages Disadvantages 1. Ability to control manufacturing, condition, quality, sterility and size of the graft before implantation 25,26 2. No donor site morbidity 3. No functional impairment 4. Better cosmetic appearance than autografts 5. They supply immediate strength to autogenous or allograft material 6. During the healing, more vigorous rehabilitation can be attempted without endangering the graft 7. It could be best fixed at bone tunnel 8. Graft can immediately withstand functional loads 9. Availability

1. Low mechanical strength 2. High failure rate 3. High characteristics of tissue reaction 4. Expensive 5. Existence of few scientific study 6. Long term results are unclear 7. High rate of rejection 8. Bioavailability and biocompatibility are concerns 9. Their biodegradability is different between commercial products

ACL, anterior cruciate ligament; HIV, human immunodeficiency virus; PDS, polydioxanone; PLGA, polyglactin.

avoidance of ethylene oxide sterilization in the new tissue preparation technologies.10,28 A variety of tendon allografts such as bone-patellar tendon-bone, Achilles tendon, anterior tibialis, fascia lata, and hamstring tendons have been used for ACL reconstructive surgery.17 Allografts have been widely used in adult ACL reconstruction with acceptable outcome. Noyes et al.18 showed 89% excellent or good results using patellar tendon and fascia lata allografts in 47 patients. Allograft bone-patellar tendonbone also has shown similar results in both short-term and long-term studies.19 The allograft tendons offer the advantage of no donor site morbidity; however, limitation of their supply and their high cost often is prohibitive.28 Allograft reconstruction of the ACL has been shown to be significantly more expensive than autograft reconstruction.18 There is concern for disease transmission as well as long-term viability.21 However, arthroscopic evaluation of ACL reconstructed knees using allograft has revealed that the tendons maintain their structure and show no biodegradation up to 59 months after reconstruction.12 Allograft tissue carries the risk of transmitting bacterial and viral diseases, including human immunodeficiency virus (HIV)

and hepatitis. Although the risk of transmission has substantially diminished because of modern screening and tissue preparation technologies, the present concern about transmission of viral disease has not been fully resolved.13 The risk of implanting an allograft from an HIV-infected donor has been reduced to one in more than 1 million.17,24 Allografts have been shown to have similar biomechanical properties to autografts, although some of the sterilization techniques have been shown to decrease the graft strength, and this has been implicated in the failure of grafts.13,23 Recent methods such as low-dose gamma irradiation have been shown to be safe for sterilization of ACL soft-tissue allograft, without compromising the biomechanical performance of the graft at early time points in rabbits.29 Application of allograft avoids using autogenous tissue, and for this reason the decreased graft site morbidity can lead to less postoperative and long-term pain.13,30 It has been shown that the final outcome of patients who underwent ACL reconstruction using allograft was fairly similar to those of autografts.12 On the other hand, it also has been shown that the healing process of the patients who received allografts was lower than those of autografts. There are some evidences that revascularization and replacement by host

Current Orthopaedic Practice

cells and collagen fibers takes longer for allografts than for autogenous grafts, which suggests that prolonged protection of the knee may be advisable after an allograft procedure.13 For these reasons, allograft could be considered suitable graft material for skeletally immature patients because their healing response is faster.21 Andrews et al.30 reported the outcomes of eight patients who had reconstruction with fascia lata or Achilles tendon allograft through a transphyseal tibial drill-hole and an over-the-top position on the femur. No patients reported giving way, and four patients returned to their preinjury level of athletics.

OTHER OPTIONS Processed xenografts can be considered as another option, but their effectiveness is still under debate.10 Tissueengineered artificial ligaments have been shown to have some distinct advantages; these include the ability to control manufacturing, condition, quality, sterility, and size of the graft before implantation.10 Mechanically tested and controlled grafts could be made available off the shelf and eliminate the need to create a second defect site through the harvesting of healthy tissue.31 Use of a prosthetic device for complete replacement of the ACL has met with various degrees of acceptance around the world.13 A theoretical advantage of ligament augmentation devices is that they supply immediate strength to autogenous or allograft material so that during the revascularization and remodeling stages of healing, more vigorous rehabilitation can be attempted without endangering the graft. Prosthetic devices can be securely fixed to bone so that the graft can immediately withstand functional loads.13 Another advantage is related to reduction of the morbidity from harvesting a tendon or fascia from the patient and, thus, minimizing the amount of dissection that is needed for the reconstructive procedure.13 Guo et al.25 investigated the surgical technique and shortterm effectiveness of ACL reconstruction with Ligament Augmentation and Reconstruction System (LARS; JK Orthomedic, Quebec, Canada) artificial ligament. Eighty patients, 51 men and 29 women, between 17--43 years of age, with ACL injury were arthroscopically treated using a LARS artificial ligament. They failed to comprehensively analyze the efficacy of this device, and they suggested that a proper clinical result only could be achieved if the technique is well applied. These structures have no cellular elements; there are no well-approved scientific studies that have tested the inflammatory response due to host defense mechanisms after surgical implantation of these products.26 Ligament-augmentation devices have been studied on a limited basis, and although early results have been encouraging, no investigation has demonstrated these devices to be clearly superior to the present autogenous graft techniques.10,13 Many studies have demonstrated their early success, but, as far as we know, no long-term investigations have shown convincingly that these constructs remain intact or that they fulfill the functional ability of the ACL effectively.13 Unfortunately, most artificial ACLs have suffered from low mechanical strength and in some cases biological insufficiencies and have been removed from the market. In the early

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postoperative stages, most failures occurred in the bone tunnels.27 Fatigue, fretting, and wear have resulted in an unacceptably high rate of failure. Thus, it seems replacement with a prosthesis in the ACL has limited value in ACL reconstruction, and tougher regulatory measurements should be applied to ensure the safety and efficacy of these commercial scaffolds.13

AVAILABLE AUTOGENOUS GRAFT OPTIONS Because the autografts are the choice and gold standard for ACL reconstructive surgery, their significance and available options are briefly discussed.

Bone-Patellar Tendon-Bone or Patellar Tendon Grafts For the past few decades, patellar tendon autograft has been the gold standard for ACL reconstruction. The reasons for this include superior fixation, less stretching, reduced reruptures, low morbidity, late onset arthrosis, proper ultimate strength and stiffness of the tissue, relative ease of harvest, structural similarities, possibility of early vigorous rehabilitation, and bone-to-bone healing with secure fixation13,32 (Table 2). This graft is harvested from the central third of the patellar tendon with bone blocks from the patella and tibia. Patellar tendon graft provides both the tensile load and stiffness similar to that of an intact ACL.9 The main advantages of bone-patellar tendon-bone reconstruction arise because it provides the most physiological reconstruction, having a natural insertion site of the tendon preserved on the bone plug.33 The bone plug in the femoral tunnel can be fixed so that the tendon is flush with the outlet and does not suffer the ‘‘windshield wiper’’ effect that occurs when the hamstring tendon rubs over the rim of the outlet of the tunnel.34 The most rapid healing time at the insertion sites found with this graft choice with bone-tobone (block-to-tunnel) union occurs within 4--6 weeks, similar to fracture healing.35,36 Another advantage is the possibility to place more tension on the bone-patellar tendon-bone graft by using the ‘‘block and tackle’’ technique on the tibial bone plug; this allows rigid fixation of the tibial bone plug to the tibial post screw.34 One of the disadvantages of the interference screw fixation in the tibia is the presence of a soft tibial bone that results in dislocation of the screw from its initial location.34 Use of the central third of the patellar tendon as an autograft has been associated with donor-site symptoms and is one of the major limitations of this graft.1 Whereas complications such as postoperative arthrofibrosis, patellar fracture, patellar tendinopathy, patellar crepitus, patellar tendon rupture, flexion contracture, functional deficits, and tunnel widening are rare, the incidence of patellar pain seems to be relatively high in some studies.1,15,34,35,37--39 Postoperative pain associated with this graft in the anterior knee has been shown to be from 4--57%.1,40 Some surgeons have suggested that anterior knee pain after graft harvest is caused by the development of patellar baja.1,38 An important factor for limitation of the donor-site problems in bone-patellar tendon-bone autografts seems to be postoperative management; to solve this problem, an



TABLE 2. Advantages and disadvantages of various autografts used in ACL reconstruction Bone-patellar tendon-bone grafts current status: gold standard Advantages Disadvantages Higher softtissue grafttunnel healing

Negative effect on the knee extensor mechanism

Optimal bone-tunnel fixation or superior fixation Less stretching

Morbidity associated with the harvest of the bone-to-bone graft

Reduced re-ruptures Low morbidity

Anterior knee pain

Hamstring tendon grafts current status: recently popular Advantages Disadvantages Acceptable results with long-term outcome

Slower and weaker soft-tissue grafttunnel healing than bone-to-bone Functional hamstring weakness resulting from graft harvesting

Rehabilitation protocol is less aggressive than bone-to-bone

Patellar fracture

Lack of bony attachment

Patellar tendinopathy

Late onset arthrosis

Patellar crepitus

Fixation of the hamstring in the bone tunnel is of concerns

Proper ultimate strength and stiffness of the tissue Relative ease of harvest

Patellar tendon rupture and flexion contracture and functional deficits Increased rate of contralateral rupture of the native ACL Weakness of the quadriceps Higher incidence of thigh atrophy

Patients are less likely to return to full activity

Structural similarities Most physiological reconstruction

Quadriceps tendon graft current status: under research Advantages Disadvantages Provides a large tendinous graft with a bone plug on one end of the graft

Long-term outcome is not clear

Similar biomechanical properties compared with bone-to-bone

Morbidity of disrupting the extensor mechanism

Facilitates bone-to-bone fixation

Less cosmetic

Provides early osteointegration Lower incidence of anterior knee pain at 1year follow-up Provide an option for revision ACL reconstruction or in multiple ligamentous injuries

High rates of failure and rupture at bone tunnel site Higher knee joint laxity

ACL, anterior cruciate ligament.

immediate and aggressive rehabilitation program after bonepatellar tendon-bone autograft harvest has been recommended.1 Several therapeutic regimens have been tested to reduce subjective pain at the donor-site level after ACL reconstruction with bone-patellar tendon-bone graft. Platelet-rich plasma (PRP) has been shown to be effective treatment;41 however, this approach deserves further investigation to confirm PRP efficacy and to elucidate its mechanism of action. Taylor et al.42 suggested that application of PRP in tendon and ligament injuries had no adverse reactions and resulted in several potential advantages, such as faster recovery and, possibly, reduction in recurrence; however, this was based on only three randomized clinical trials. It seems that the functional deficit associated with harvesting the central third of the patellar tendon is relatively low and, if present, it usually resolves after 3--6 months.1 Weakness of the quadriceps also has been described as a potential problem after patellar tendon autograft reconstruction.35,36 It has been reported that patients with ACL reconstruction using bone-patellar tendon-bone graft had a higher incidence of thigh atrophy at 1 year after operation, but no significant difference has been demonstrated at 2-year follow-up when compared with hamstring graft.9,15

An increased rate of contralateral rupture of the native ACL in those patients who had received the bone-patellar tendon-bone graft also has been recorded.9 Struewer et al.43 re-evaluated 73 patients, average 13.5 years of age, after ACL reconstruction using patellar tendon autograft. Their radiographic assessments have shown that tunnel widening remains a potential radiographic phenomenon, which is most commonly observed within the shortterm to mid-term intervals after reconstruction and subsequently stabilizes on mid-term and long-term followup. They have concluded that it does not adversely affect long-term clinical outcome and stability.

Hamstring (Gracilis and Semitendinosus) Tendon Graft More recently, the hamstring tendon has joined the patellar tendon autograft in popularity.21,32 The patellar tendon may no longer be considered the ‘‘gold standard,’’ with more surgeons choosing the hamstring tendon as their graft of choice, and studies are showing long-term successful results.5,44 Use of the hamstring tendons has the following advantages compared with application of the patellar tendon: damage to the extensor mechanism is avoided, postoperative


parapatellar pain is lessened, less quadriceps weakness results, and less frequent fractures of the patella or disruption of the patellar ligament occur (Table 2).1,2,8,15 In addition, harvesting of the hamstring tendons is associated with less graft-site morbidity and is less difficult technically than preparation of bone-patellar tendon-bone grafts.13,45 They provide higher structural properties when folded to a tripled or quadrupled construct and replicate the nonisometric behavior of the intact ACL (with its anteromedial and posterolateral bundles) more closely than a single-stranded graft.45 Harvesting the hamstring tendons does not significantly compromise strength or function of the leg.46 Subsequently, the rehabilitation protocol for patients has been less aggressive after reconstruction using a hamstring graft.47 An advantage in application of the hamstring tendon graft is avoidance of interference with the extensor mechanism of the knee. Despite removing two of the three medial muscular stabilizers of the knee, the functional deficit after semitendinosus and gracilis tendon harvest seems to be minimal. Three years after ACL replacement using hamstring tendon graft, the mechanical strength of the hamstring muscle has been reported to be around 95% of the preoperative values. Overall, harvesting of the hamstring tendon does not cause major functional impairment for patients who have undergone ACL reconstruction.1 The two most important issues for patients who have undergone ACL reconstruction are knee stability (in the relative short-term) and development of osteoarthritis (in the long-term).1,9 It has been suggested that after ACL reconstruction, there is a lower risk of radiographic degenerative joint disease with hamstring tendon rather than bone-patellar tendon-bone grafts at 7 years after surgery.32,34,48 Nevertheless, despite their increasing popularity, hamstring tendon grafts have potential limitations, such as greater elasticity and slower soft-tissue graft-tunnel healing capacity compared with bone-to-bone healing with patellar tendon grafts. Other limitations in the use of hamstring tendon grafts are the longer time requirement for the tendons to become fixed to bone within the osseous tunnels, less secure fixation to bone, potential for tunnel widening and graft laxity, possible postoperative elongation of the tendon, and functional hamstring weakness resulting from graft harvesting (Table 2).49,50 These tendon grafts are not attached to bone blocks, a requirement for tendon-tobone healing, which may necessitate an extended time for graft incorporation. Therefore, sufficient fixation of these grafts especially during the early postoperative time when osseous graft incorporation has not been completed is crucial.45 Although there is little controversy on the fixation technique for patellar tendon grafts, no consensus has been found on the fixation of hamstring tendon grafts. Seo et al.51 followed 127 patients who underwent arthroscopic ACL reconstruction, using autologous hamstring tendon for more than 1 year. Rigidfixs (DePuy Orthopaedics Inc., Warsaw, IN) was used in 71 patients, and PINN-ACL Crosspin (Conmed Linvatec Inc., Largo, FL) was used in 56. They showed no difference between the employment of PINN-ACL Crosspin and Rigid-fix as femoral graft fixation for ACL reconstruction with hamstring tendons. However,


the PINN-ACL Crosspin led to complications with extensive operation time. They suggested that further improvement in the tools would be necessary to minimize the complications. Fixation of the hamstrings continues to be an area of concern. Early in the postoperative period the graft fixation needs to be able to withstand the forces that are applied upon the graft. Past methods of hamstring tendon fixation have not provided the strength or stiffness seen with the bone-patellar tendon-bone graft fixation.52 Lack of bony attachment in the hamstrings raised concern about incorporation of the graft. The tendons must incorporate within the bone, a longer process in hamstrings than bone-to-bone integration. Animal studies have shown that the tendons are not incorporated until 3 months postoperatively.47 Feller et al.53 demonstrated high rates of failure of bone filling the graft tunnels in the hamstring groups, which did not occur in the bone-patellar tendon-bone group. Bizzini et al.49 showed hamstring reconstructions to have significantly greater knee joint laxity on arthrometer testing when compared with bone-patellar tendon-bone reconstruction. The hamstring tendon connection is an indirect one, made between the tendon and the newly-woven bone by connective tissue known as Sharpey’s fibers. There also is strong evidence from animal studies to suggest that, because of a variety of biochemical and biomechanical insults, hamstring healing of tendon graft in the bone tunnel is delayed and weaker.21,54 The most conceptually secure way to fix a quadruple hamstring is with a Transfix bar (Arthrex Inc., Naples, FL) into the femur to prevent damage to the tendon with an interference screw. However, a ‘‘windshield wiper’’ effect should be expected as well as increased tunnel size, which is more common in hamstrings than in patellar tendon reconstructions.34 Fixation of the hamstring graft within the femoral tunnel with a screw also can compress and squash the tendon fibers; it does not always guarantee formation of the Sharpey’s fibers and tendon healing in all cases. Proponents of hamstring grafts have realized this and have developed reverse thread screws to attempt to solve this problem.9 Bourke et al.55 reported the mid-term outcome of 200 patients who had reconstruction using fourstrand hamstring tendon graft with anteromedial portal femoral tunnel drilling and interference screw fixation. Their results indicated that there was no increase in laxity of the graft over time with this technique. The increased tunnel expansion may be indicative of nonhealing of the tendon in the tunnel and excessive movement. Distal fixation of hamstrings is still often performed with staples, but attempting to use an interference screw for fixation in the tibia increases the tendency to push the graft towards the joint as the screw is inserted despite simultaneous pulling on the tendon. Despite these concerns, however, the overall outcome has not been reported to be statistically different compared with patellar tendons.13 Aune et al.13 assigned 72 patients with subacute or chronic rupture of the ACL to autograft reconstruction with four-strand hamstring tendon (n ¼ 37) or with bone-patellar tendon-bone (n ¼ 35) graft from the ipsilateral side. Their follow-up after 6, 12, and 24 months showed no differences between the groups with respect to


the Cincinnati functional score, KT-1000 arthrometer measurements, or stair-hopping test results. The subjective results and the single-legged hop test results were better for the hamstring tendon group after 6 and 12 months, but no differences were found after 24 months. The hamstring tendon group showed better isokinetic knee extension strength than did the patellar tendon group. There was a significant weakness in isokinetic knee flexion strength in the hamstring tendon group. Kneeling pain was significantly less common in the hamstring tendon group after 24 months. The results of that study showed a trend toward better subjective results, quadriceps muscle strength, endurance, and functional performance after 6 months when a hamstring tendon graft had been used rather than a patellar tendon graft.13

Quadriceps Tendon Graft The quadriceps tendon is a graft preferred by some. The advantages and disadvantages of this type of graft are provided in Table 2. It provides a large tendinous graft with a bone plug on one end of the graft.1 A 10-mm wide quadriceps tendon graft has a larger cross sectional area than a similar sized bone-patellar tendon-bone graft. The ultimate tensile load of the human quadriceps tendon graft has been shown to be 2352 ± 495 N, which is similar to a bone-patellar tendon-bone graft.56 The bony plug also facilitates bone-tobone fixation within the femoral tunnel, which allows for early osteointegration similar to bone-patellar tendon-bone.1 Tibial fixation can be achieved by using many of the softtissue fixation methods that are used for the hamstring graft.56 This is a graft that is used less frequently than all other autogenous grafts, and there are few studies evaluating longterm outcome.1 Studies that have evaluated this graft show no differences in 1-year outcomes when compared with the bone-patellar tendon-bone graft.13 Other reports have shown a low incidence of anterior knee pain at 1-year follow-up.57 The quadriceps tendon graft harvest has the potential morbidity of disrupting the extensor mechanism, is cosmetically less pleasing (the size and location of the donor-site scar), and does not afford the advantage of bone-to-bone integration at both the tibia and femur.9 While bone-patellar tendonbone and hamstring tendon remain the most commonly used autogenous grafts, the quadriceps tendon graft does provide an option for revision ACL reconstruction and reconstruction in knees with multiple ligamentous injuries when allograft is not available.56

DEFINITIVE ARGUMENT ABOUT AVAILABLE GRAFT CHOICES The advantages and disadvantages of each graft option have been discussed in details. Although many different options have been demonstrated in this review, the autogenous grafts are still the most valuable options in ACL reconstructive surgery and can be suggested as a gold standard in ACL reconstruction. Generally, this statement is in agreement with most of the reviews and research articles published in the last decade.9,15,19,28,48 Despite previous studies, allografts are an option in ACL reconstructive surgery and should be selected


when limitation of autogenous grafts would be of great concern for the patient. To date, there is no well-accepted opinion about the best graft options among the autogenous grafts. Perhaps the controversies are the most significant issues in this point, and some potential bias and conflicts of interests should be considered to explain these controversies. Additionally, individual variations in the patients, such as age, sex, and life style as well as the surgical methods, could significantly affect the outcome of the studies and should not be dismissed. This review suggests that patellar tendons and hamstring tendons are the gold standard for ACL reconstructive surgery; however, the final decision should be made by the surgeon. As we mentioned in this review, both patellar tendon and hamstring tendon autografts have some advantages and disadvantages, and here we compared the overall outcome of these autografts options and entrust the final decision to the readers. Clinical studies have demonstrated that these two graft choices have similar rates of effectiveness in adults, with minor differences in postreconstruction knee stability, and muscle strength and activity levels at 2 and 5 years after implantation.1,13 Li et al.58 demonstrated that ACL reconstruction with hamstring tendon or bone-patellar tendonbone autografts achieved similar postoperative effects in terms of restoring knee joint function. Hamstring tendon autografts were inferior to bone-patellar tendon-bone autografts for restoring knee joint stability but were associated with fewer postoperative complications. In a recent study, Gifstad et al.59 evaluated 114 patients with asymptomatic ACL rupture after they were randomly reconstructed with either a patellar tendon (n ¼ 58) or a hamstring tendon (n ¼ 56) graft. Their results showed that both grafts resulted in satisfactory subjective outcome and objective stability, and there were no significant differences between these surgical procedures. The methods of preparation of the hamstring tendon grafts (1--4 strands) could determine the clinical outcome and make this graft type comparable or even better than the gold standard patellar tendon grafts.60 The structural strength of a hamstring tendon graft, with all four strands equally tensioned at time zero (4590 N), is superior to that of a 10-mm bone-patellar tendon-bone graft (2977 N).13 In a recent prospective longitudinal study, Leys et al.57 compared the results of isolated endoscopic ACL reconstruction using a four-strand hamstring tendon or patellar tendon autograft over a 15-year period with respect to reinjury, clinical outcomes, and development of osteoarthritis. Patients who received the patellar tendon graft had significantly worse outcomes compared with those who received the hamstring tendon graft for the variables of radiographically detectable osteoarthritis (P ¼ 0.04), motion loss (P ¼ 0.03), single-legged hop test (P ¼ 0.001), participation in strenuous activity (P ¼ 0.04), and kneeling pain (P ¼ 0.04). ACL graft rupture occurred in 17% of the hamstring tendon group and 8% of the patellar tendon group (P ¼ 0.07). The ACL graft rupture was associated with nonideal tunnel position and male sex. Contralateral ACL rupture occurred in significantly more patients with patellar tendon grafts than patients with hamstring tendon grafts (P ¼ 0.02). Their results showed that the hamstring tendon autograft had better outcomes than the


patellar tendon autograft in all these outcome measures. Additionally, at 15 years, the hamstring tendon graftreconstructed ACLs have shown a lower rate of radiographic osteoarthritis. In another experiment, Genuario et al.61 showed that ACL reconstruction with hamstring tendon autograft is the most cost-effective method of surgery for the average patient with ACL deficiency. O’Neill62 compared three techniques for ACL reconstruction. One hundred twenty-seven patients with a torn ACL received either a single or two-incisional reconstruction using patellar tendon graft, or a two-incision reconstruction using a double-stranded hamstring tendon graft. The patients who were treated with a two-incisional reconstruction using a patellar tendon graft returned to a greater level of athletic activity than the other two groups, and a higher percentage of the patients in this group had satisfactory stability. Aglietti et al.7 compared the two grafts by alternating graft choice in nonrandomized patients. The PT grafts were fixed by use of a post and washer on the femoral side and an interference screw on the tibial side, whereas the hamstring tendon grafts were fixed with a post and washer outside the femoral and tibial channels. Patellofemoral crepitation and minor loss of extension were more common among patients in the patellar tendon group. Return to sports was more frequent among the patients in the patellar tendon group. There were no differences in the incidence of symptoms or laxity between the groups. Mohtadi et al.63 compared the clinical outcome of 1597 young to middle-aged adults who underwent patellar tendon or hamstring tendon reconstruction and showed that the patellar tendon group resulted in a more statically stable knee compared with hamstring tendon reconstruction (P < 0.05). Conversely, patients experienced more anterior knee problems, especially with kneeling after patellar tendon reconstruction. Patellar tendon reconstructions resulted in a statistically significant loss of extension range of motion and a trend towards loss of knee extension strength. Hamstring tendon reconstructions demonstrated a trend towards loss of flexion range of motion and a statistically significant loss of knee flexion strength. The clinical importance of the above range of motion losses is unclear. Although their study was comprehensive, they failed to conclude which graft was the best in the long-term. They just concluded that while patellar tendon reconstructions are more likely to result in statically stable knees, they also are associated with more anterior knee problems. One of the major limitations of hamstring tendon grafts compared with patellar tendon grafts is their low healing ability. Janssen et al.45 studied 67 patients who underwent retrieval of midsubstance biopsies after clinically successful hamstring autograft ACL reconstruction. Human hamstring grafts showed typical stages of graft remodeling, which was not complete up to 2 years after reconstruction. The remodeling process in humans was prolonged compared with the results obtained in several animal studies. So, in this case the animal studies were of low value, and their results could not be extrapolated with confidence to humans. The hamstring tendon autografts are possibly better options than patellar tendon ones if the anchorage techni-


ques and tendon-to-bone healing is improved. Despite variable techniques aiming to improve bone tunnel healing, bone morphogenetic protein (BMP) and calcium phosphate cement are still mainstays of treatment for optimization of the healing process in this purpose. In a recent study, Hashimoto et al.64 attempted to generate a bone-tendonbone structure by injecting human-type recombinant human bone morphogenetic protein-2 (rhBMP-2) into the hamstring tendons, and the ACL defect was reconstructed by grafting the engineered bone-tendon-bone graft. Biomechanical pull-out testing showed that the ultimate failure load and stiffness of the reconstructed ACL in the experimental group were significantly higher than those in the control group at both 4 and 8 weeks (P < 0.05). These results indicate the potential of regenerative reconstruction of the ACL, and the reconstruction resulted in restoration of morphology and function equivalent to those of a normal ACL. Pan et al.65 also compared the effect of osteointegration of grafted tendon in bone tunnels between the injected calcium phosphate cement (ICPC) and injected fibrin sealant (IFS) combined with BMP after ACL reconstruction in 51 rabbits. After 2, 6, and 12 weeks, biomechanically, the ultimate failure load in the ICPC-BMP group was always higher than that in the IFS-BMP group. It is evident that the ICPC composite achieved a more prolonged osteogenic effect than that by IFS composite. Nebelung et al.66 evaluated midterm outcomes after transfemoral graft fixation using either a conventional or a modified technique and additional bone plug augmentation (BPA) of the femoral tunnel aperture after ACL reconstruction with a quadrupled hamstring autograft in 56 patients. They found that additional BPA has the capacity to improve morphological and clinical outcomes at 5-year follow-up. Allografts also are valuable options if the limitations of autogenous grafts are of great concern to patients. Kim et al.67 evaluated the effect of hamstring harvesting in 73 consecutive patients who underwent ACL reconstruction. Thirty-nine patients whose hamstrings were harvested for autografts were compared with 34 patients who received allografts during the same time period. Their results indicated significant knee flexion weakness compared with the unaffected knee after ACL reconstruction regardless of hamstring harvesting. Moreover, the greater increase in knee flexor deficit in the hamstring-harvested group compared with the allograft group was statistically significant. However, the clinical and functional outcomes were similar between the groups. Aslan et al.28 investigated the clinical outcome of ACL reconstructions with allograft or autograft. They evaluated 82 patients who underwent arthroscopic ACL reconstruction with patellar tendon allograft (n ¼ 52) or hamstring tendon autograft (n ¼ 30). The patients were assessed using the International Knee Documentation Committee (IKDC) and Lysholm knee scores and functional (one-leg hop) and laxity (pivot-shift, Lachman, anterior drawer) tests. There was no statistically significant difference between the groups with respect to IKDC and Lysholm scores, functionality and ligament laxity (P > 0.05). However, effusions were more frequent in the hamstring tendon group compared with the patellar tendon group. They showed that differences in graft options for ACL reconstruction have no effect on the clinical outcome. In


another more recent study, Rice et al.12 determined the optimal decision between autograft and allograft for patients undergoing ACL reconstruction. Expected-value decision and sensitivity analyses were performed to systematically quantify the clinical decision. Their results indicated that autograft is preferred over allograft for ACL surgical reconstruction. Pallis et al.14 showed that in a young, active cohort, individuals having undergone an ACL reconstruction using allograft were significantly more likely to experience clinical failure, requiring revision reconstruction compared with those who underwent autologous graft reconstruction. They recommended autograft use in ACL reconstruction in young athletes. Xenografts, synthetic, hybrid, and tissue-engineered grafts are still under investigation but it seems that some of them may be considered as the future options. For now, they are not recommended for ACL reconstruction in human beings.16,68--74

BONE TUNNEL HEALING Because of insufficient healing potential in the bone tunnel or abrasion of the graft at the tunnel exit, all types of ACL reconstruction are associated with a proportion of grafts failure.71 Tendon-bone incorporation of a tendon graft within the bone tunnel is a major concern when using a tendon graft for ligament reconstruction. Successful ACL reconstruction with a tendon graft requires solid healing of the tendon graft in the bone tunnels. Improvement of graft healing to bone is crucial to facilitate early and aggressive rehabilitation and a rapid return to full activity. Healing of a tendon graft in a bone tunnel requires bone ingrowth into the tendon. Indirect Sharpey fibers and direct fibrocartilage fixation of the tendon-bone interface provide different anchorage strength and interface properties.10 The insertion of the native ACL is characterized in four layers: tendon, fibrocartilage, mineralized fibrocartilage, and bone.27 The collagen fibers of the tendon extend into both the fibrocartilage and the mineralized layer. This structure usually is destroyed when the ligament is removed and the bone tunnel is drilled. A replication of this direct type of insertion may be considered desirable when assessing bone tunnel healing for ACL grafts.27 Based on normal ACL structure and function of the insertion site, the ideal tendon graft would attach broadly to the surface of the bone at the femoral and tibial attachment sites by an intermediate zone of fibrocartilage. The bone-patellar tendon-bone graft undergoes a process of ligamentization. The graft undergoes initial processes of necrosis, revascularization, cellular proliferation, and then remodeling. The remodeling phase could be divided into consolidation and maturation phases. The biochemical and morphologic changes occur in the graft as it assumes a histologic pattern similar to native ACL, but it is not identical to either native ACL or tendon.23 The most rapid healing time at the insertion sites is in patellar tendon autograft or allograft with bone-to-bone healing times of 4--6 weeks. This graft has the additional benefit of having the natural insertion site of tendon preserved on the bone plug as previously described.


The mechanism by which graft-bone healing occurs depends on the type of the graft used. For bone-patellar tendon-bone grafts, healing in the tunnel resembles normal fracture healing but may be a more complex process. Incorporation of the bone block in the tunnel has been observed as early as 16 weeks after surgery.23 Bone-patellar tendon-bone grafts have the advantage of allowing rigid fixation of the graft in the bone tunnel. The tendon-bone healing process occurs through a different mechanism after implantation of a soft-tissue graft without bone plugs.23,47 First, fibrovascular interface tissue forms between graft and bone, and progressive mineralization of the interface tissue occurs with subsequent bone ingrowth into the outer tendon and incorporation of the tendon graft into the surrounding bone.10,75 Sharpey’s fibers are made up of type I collagen and connect the periosteum to the bone. Progressive reestablishment of the continuity of collagen fibers between the tendon and the bone results in re-establishment of a tendoosseous junction.16 Formation of the Sharpey-like fibers within the bone tunnel often are identified as a marker of indirect healing between the tendon and bone.76,77 Formation of these collagenous fibers may start from 6 weeks after surgery.16,76 However, complete bone tunnel healing of an ACL graft may occur as late as 6--12 months after surgery.23,77,78 Some studies in the animal models suggest that tendon graft incorporation occurs more slowly than bone-patellar tendon-bone healing.75,79 In addition to the choice of graft, surgical fixation, graft position, and interfacial motion within the bone tunnel may affect healing.27 Graft motion within the bone tunnel has been shown to be inversely proportional to healing in animal models.16,75--78,80 Histology taken at revision surgery for mid-substance tears, shows that free hamstring tendon autograft has adequate osteointegration between 6--15 weeks.81 If soft tissue-to-bone integration occurs at this time in the postoperative time period, a hamstring tendon graft may allow for earlier recovery and return to activity because of less donor site morbidity. A number of studies have shown no significant difference in clinical outcomes between bone-patellar tendon-bone graft and hamstring tendon graft for ACL reconstruction.6--8,82 The healing potential of a ruptured ACL as described before is considered to be extremely poor.4,83 It is suggested that the intraarticular environment that inhibits ACL healing also may interfere with bony healing in the proximal parts of the osseous tunnels.33

STRATEGIES TO ENHANCE TENDON GRAFTBONE TUNNEL HEALING New biological strategies are evolving to improve the intraarticular and intraosseous healing potential of the ACL grafts.10 Although these biological engineering strategies currently are experimental, they are expected to be used in clinical application in the near future. Tendon graftto-bone healing could be improved by application of brushite calcium phosphate cement, injectable tricalcium phosphate, mesenchymal stem cells, hyperbaric oxygen treatment, transforming growth factor-beta 1 (TGF-b1), calcium phosphate, bone marrow, demineralized bone



matrix, synovial mesenchymal stem cells, Poly sulfated glycosaminoglycans, hyaluronic acid, granulocyte colonystimulating factor, serotonin S2 blockers, magnesium-based bone adhesive, BMP-2, low-intensity pulsed ultrasound, and shock wave therapy.22,27,84--102 Strategies to improve the tendon-bone tunnel healing have focused on providing appropriate molecular signals and cell differentiation resulting in an effective healing response between tendon and bone.10 Most of these strategies involve the use of osteoinductive cytokines.87,92,98--100 The osteoconductive materials also may play a role in improving tendon healing in a bone tunnel through enriched bone ingrowth.16,84,85,89,101 The beneficial effects of the granulocyte colony stimulating factor (GCSF) is related to the production of granulocytes and stem cells in bone marrow, differentiation of neutrophils, angiogenesis, and differentiation and migration of mesenchymal stem cells. It has been suggested that GCSF enhances the ultimate strength and accelerated bone development of the graft in experimental ACL reconstruction in adult beagle dogs.92 Application of growth factors such as basic fibroblast growth factor (bFGF) and vasculoendothelial growth factor and stem cells merits further investigation but is not immediately clinically applicable. It recently has been shown that administration of bFGF resulted in enhanced mesenchymal cell proliferation, collagen preservation, enhanced neovascularization and circulation, improved tissue maturation, which resulted in increased structural and mechanical properties of the injured tendons.96,103 Calcium phosphate (CaP) in the forms of hydrogel, porous, cement, and injectable forms has been shown to have a powerful role on ACL-bone tunnel fixation strength and healing of the bone and results in improved bone densitometry.27,70,74,88,90,92,98,104 BMPs are signaling proteins that influence tissue structures in the body, and they have a role in skeletal development. Both BMP-2105,106 and BMP-7104 have been shown to increase the graft fixation strengths when applied in the bone tunnels in animal models. Likewise, BMP-7 has been shown to increase the volume of bone formed within the tunnels 6 weeks after implantation.104 However, Rodeo et al.98 found that the difference in strength between the grafts treated with BMP-2 and controls diminished over time (as measured 8 weeks after surgery). This implies that these products induce faster healing but not necessarily stronger fixations in the long-term. Application of the recombined bone xenograft within the bone tunnels after ACL replacement has been shown to have beneficial effects on the ultimate strength of the grafts after 12 weeks after injury in rabbits.74 The demineralized bone matrix (DBM) is a further source of BMPs, which has been proposed as a mean of enhancing tendon-bone healing and tendon-bone fixation strength by inducing an increase in the growth of fibrocartilage and mineralized fibrocartilage at the tendon bone interface in ovine.83 A combination of BMPs and implanted periosteal progenitor cells has been shown to increase the ultimate strength and inhibit the samples to pull out the tibia after 3 and 6 weeks, after reconstruction.72 Similar results to those found for BMPs were observed after application of a bone-derived extract, 2, 4, and 6 weeks after surgery.107

Hyaluronic acid (HA) has been shown to have promising curative effects on tendon-bone healing in rabbits.69 A direct bond was shown to be formed between the tendon and the bone.69 Several physiochemical aspects of HA are beneficial for biomaterial fabrication and application and can transduce intrinsic signals within a structure, thereby enhancing tissue formation and playing a crucial role in promoting cell differentiation and cell growth.68,108 Briefly, the promising curative effects of HA on tendon healing have been shown to be related to cellular proliferation, collagen preservation, reduced inflammation, tissue alignment, and maturation.97 Application of the materials seeded with the mesenchymal stem cells (MSCs), from which osteoblasts are derived, also has been shown to increase the ultimate strengths and improve bone tunnel healing.27 A sufficient population of stem cells is likely required for optimal tissue regeneration. The mesenchymal stem cell-treated grafts have cartilage at the tendon-bone interface and periosteum, which consists of multipotent mesodermal cells.22,88,90,91 It also contains chondroprogenitor and osteoprogenitor cells that can form both cartilage and bone under appropriate conditions.10 A number of studies3,79,109 have found improvements in intratunnel bone development and increase in the ultimate strength by using this technique. It has been shown that the injectable poly (ethylene glycol) diacrylate (PEGDA)--based polymer hydrogel with periosteal progenitor cells and BMP-2 enhance tendon graft-bone healing.10 It is stated that satisfactory results can be achieved with a periosteum-enveloping hamstring tendon graft in ACL reconstruction.10 Kawai et al.73 showed that application of chitin or chitosan to a polyester fabric significantly increases the ultimate strength and bone formation in the short-term in a rat model. Hyperbaric oxygen, low-intensity pulsed ultrasound and extracorporeal shockwaves could induce marked increases in vascularity that improves new bone formation.86,101,102 Shock wave treatment significantly improves the healing rate of the tendon-bone interface with significantly more trabecular bone formation around the tendon.102 These various methods demonstrate the challenge of achieving secure biological fixation of tendon grafts in a bone tunnel with current ACL reconstruction techniques. Based on the finding that tendon-bone healing progresses by bone ingrowth into the fibrous tissue interzone, the exogenous osteoinductive agents should be used to augment this healing.10

THE FUTURE There are several research areas with well-developed surgical techniques in the field of reconstructive surgery; however, the most significant area of concern is focused on graft selection, improvement of healing response in bone tunnels, and postoperative and rehabilitation protocols.9,53,110 The autografts and allografts have some significant limitations.24,49 New approaches in tissue engineering could be suggested to substitute the traditional grafts that were previously designed for ACL reconstruction. Both synthetic and biologic options could be developed with the knowledge of tissue engineering. However, hybridized biodegradable biocompatible implants are of more value and are possibly the candidates to substitute the traditional grafts. The collagenic materials are interesting with the most


powerful biologic effects but they have less strength and stiffness than autografts, allografts, or synthetic implants.111,112 A combination of collagen with high mechanical strength artificial biodegradable and biocompatible materials could solve this problem and make these new products more attractive. These three-dimensional implants could be designed with stem cells seeding and some of the important materials necessary for tissue growth such as glycosaminoglycans and a varieties of growth factors.68,87,88,91 Gene therapy could enhance the behavior of the seeded cells in a manner to improve bone healing response at bone-implant interface.22,96,97,100,103 These new implants should consist of three different areas of ligament, fibrocartilage, and bony plug structure, manufactured by in-vitro and then implanted in vivo by tissue engineering technologies.76,84,99 The focus area for ACL engineering is the bone-to-bone interfaces.23 Many materials such as the described ones should be attached to this bony plug to complete the artificial tissue. Postoperative rehabilitation modalities should be expanded in long-term studies at different age groups, both in humans and animal models.53

CONCLUSION The patellar tendon autograft has some mechanical and biological properties that are advantageous but offer higher graft site morbidity and less cosmesis. The hamstrings grafts are cosmetically more pleasing and offer less donor site morbidity but are slower to incorporate, and the initial fixation historically has been an issue. Quadriceps tendons are thicker, have intermediate morbidity and decrease the operative time but have the worst cosmesis and have soft-tissue fixation concerns on one end with slower incorporation. The patellar tendon allograft has no donor morbidity, good initial fixation, decreased operative time, but costs are higher and there is a slight risk of disease transmission. Although use of different types of autografts and allografts such as bone-patellar tendon-bone complex or hamstring tendon should be considered as gold standard graft types for ACL reconstructive surgery, application of these types of grafts have some limitations as well as some adverse effects. These types of grafts have not yet provided a well-approved solution in ACL reconstructive surgery. Other options such as xenografts and tissue engineering are not commercially available as yet, and to the knowledge of the authors limited research has been undertaken for their biocompatibility, efficacy, and outcome. Most of the engineered grafts have been used in in vitro studies, and their efficacy has not been investigated as yet on in vivo models. In vivo application of the tissue engineered materials, with or without various promising agents such as growth factors, BMPs, glycosaminoglycans, various types of cells, and other possible components, could be the most important area of research in ACL reconstructive surgery in the future. REFERENCES 1. Fu FH, Bennett CH, Ma CB, et al. Current trends in anterior cruciate ligament reconstruction: Part 2. Operative procedures and clinical correlations. Am J Sports Med. 2000; 28:124--130.


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