Graft Choices in ACL Reconstruction
The optimum type of graft for a patient undergoing reconstruction of a torn anterior cruciate ligament remains unclear, leaving the decision up to the surgeon based on patient factors and preference. In this article, the authors review evidence on the use of various autograft options, allograft, synthetic devices, and living donor allograft.
Alberto Castelli, MD; Simone Perelli, MD; Enrico Ferranti, MD; Eugenio Jannelli, MD; Giacomo Zanon, MD; and Francesco Benazzo, MD
Anterior cruciate ligament (ACL) tears are common orthopaedic injuries affecting mostly young and active patients,  with nearly 200,000 ACL reconstructions annually in the US. ACL injuries occur across all age groups, but their prevalence is higher in adolescent athletes and active adults as a consequence of the increasing intensity of sports training.  ACL insufficiency results in joint instability and altered gait kinematics, and it can lead to chronic pain and degenerative changes in the knee. [3,4,5]
Arthroscopic reconstruction is the standard approach to treating ACL tears, but the optimum graft choice remains controversial. Surgeons in the US most often use bone-patellar tendon-bone (BPTB) and 4-strand hamstring tendon autografts. [6,7] A study of surgeons in Italy showed a preference for hamstring autografts. 
Some authors have suggested that BPTB autograft is the best graft choice due to its faster integration and greater proportion of patients returning to pre-injury activity levels. [9,10] However, others prefer hamstring autograft due to reduced donor site morbidity, anterior knee pain, and lower extensor strength deficit. [11,12]
The most significant negative outcome of ACL reconstruction is graft rupture. Many prospective studies have compared BPTB and hamstring failure rates, with most studies demonstrating similar rupture rates for the 2 grafts. [9,10,13,14] A 2014 registry study based on 45,998 primary ACL reconstructions in Scandinavia found a higher risk of rupture for patients undergoing hamstring autograft than for those receiving BPTB autograft.  These findings contradict the results reported by Xie et al  in their meta-analysis.
New issues have arisen in more recent prospective and retrospective studies, including the use of quadriceps tendon graft, allograft, and new synthetic products. [15-17] Moreover, results from recent prospective cohort studies are helping to define patient and surgical risk factors for graft failure after ACL reconstruction, such as: [18-20]
- Younger patient age
- Increased activity level
- Use of allograft
Graft choice is the only one of these risk factors that the surgeon can modify. For this reason, it is imperative for the surgeon to carefully consider all graft options and to discuss with the patient the risks and benefits associated with these options.
Hamstring Tendon Graft
Budnay et al  recently reported on graft choices for ACL reconstruction among members of the American Orthopaedic Society of Sports Medicine and the Arthroscopy Association of North America. They found that 45% of respondents most commonly choose a quadrupled 2-tendon hamstring autograft, followed by BPTB autograft (41%), quadrupled single-tendon hamstring autograft (18%), and allograft (17%). In patients with open physes, 91% of respondents use hamstring autograft. 
In a recent survey, the hamstring tendon was the most commonly used graft type, with 81% of respondents indicating it is their choice for male patients and 91% saying they prefer to use hamstring grafts in female patients.  The trend was different when professional athletes were included: 49.6% of respondents prefer BPTB grafts and 44.8% use hamstring grafts for this population.  This may be due to the estimated time needed for graft integration in bone tunnels: Soft tissue autograft healing occurs 8 to 12 weeks after surgery with Sharpey’s fibers formation, [22, 23] while the bone healing process takes about 6 weeks for the BPTB graft. Moreover, a longer time – about 6 months – is needed to achieve neo-ACL incorporation in the joint in both hamstring and BPTB autografts.
However, Irvine et al  demonstrated no difference between graft types in femoral and tibial tunnel motion at 6 weeks and 1 year in a human model of walking and stair descent. This may suggest that a BPTB graft does not heal more rapidly than a hamstring graft, despite the common clinical practice of choosing a BPTB graft for patients who need a more rapid return to physical activity.
Hamstring harvesting is a standardized technique, with a small skin incision and a careful dissection of the fascia to avoid damaging the infrapatellar branch of the saphenous nerve and early amputation of the tendon during the stripping procedure. The quadrupled semitendinosus tendon or the association of the semitendinosus and gracilis tendons are both validated.
The major factor in the success of ACL reconstruction with an hamstring autograft is the size of the graft. The graft should be at least 7 mm in diameter, although recent studies have indicated that a diameter of 8 mm or more decreases the risk of graft failure. [25, 26] A preoperative MRI may be a useful tool to evaluate the thickness of the graft, as clinical anthropometric data – the patient’s weight in particular  – are predictive of hamstring graft diameter. Recent studies have indicated that preoperative 1.5 Tesla MRI evaluation of the cross-section area (CSA) of the semitendinosus tendon at the knee joint line is a reliable parameter to predict graft size. If the CSA of the semitendinosus tendon is <5.9 mm2 at the level of the joint line, a different graft alternative should be considered. 
The primary outcome measure after ACL reconstruction is graft failure. Despite many randomized comparative studies investigating differences between hamstring and BPTB grafts, registry and aggregate data show similar results, with a BPTB graft failure rate of 7.0% and a hamstring graft failure rate of 3.9% in long-term follow-up studies. In addition, return to the pre-injury sports level seems to be similar with hamstring and BPTB grafts, [12,19,29] and there is minimal difference between the 2 in patient-reported outcome measurements (PROMs).
Recent studies have shown some increased knee joint laxity with the use of hamstring grafts compared with BPTB grafts. In particular, athletically active females who had hamstring grafts demonstrated internal tibial rotation weakness based on KT-1000 arthrometer measurements and clinical examination.  Hamstring harvesting may also be associated with impaired lower extremity knee flexor and internal rotator strength. Knee flexor strength impairment may limit the results of athletic high-speed sprinting and directional change movements when hamstring muscles are activated.  EMG studies, however, have shown that having a harvested hamstring autograft does not result in a significant neuromuscular, biomechanical, or strength deficiencies, with patients exhibiting neuromuscular adaptation to stabilize the knee and protect the reconstructed graft. 
Data are lacking on how safe it is to use a hamstring autograft; however, this type of graft generally provides a good clinical result in terms of graft failure, stability, and patient satisfaction, and it remains the best choice for patients with open physes.
The use of hamstring tendon grafts has grown in the last 10 years, but BPTB grafts are still important. In a recent survey, 41% of surgeons from North America said they choose BPTB grafts for primary ACL reconstruction in adult patient.  Interestingly, use of BPTB graft increased in patients categorized as athletic (57% for females and 61% for males) because BPTB graft is thought to allow more rapid return to sports, although that conclusion remains questionable.
Both hamstring and BPTB grafts exhibit similar strength and mechanical properties.  The healing process in the bone tunnels at the insertion site is quicker if a bone block is used because it can heal like a fracture within 6 weeks.  Irvine et al  showed no difference between graft types in femoral or tibial tunnel motion at 6 weeks and 1 year in a walking and stair descent model.
The harvesting technique for BPTB grafts requires 1 or 2 skin incisions, with the graft obtained through harvest of patellar and tibial tuberosity bone blocks of 20 to 25 mm and an approximately 8- to 10-mm bundle of the medial third of the patellar tendon. In the survey of North American surgeons, nearly all surgeons bone grafted the donor site (83.8%) and closed the defect in the patellar tendon (78.5%).  This procedure avoids issues related to the size of the graft.
Donor site morbidity remains a concern, with a risk of:
- Kneeling pain [34,35]
- Anterior knee pain [36,37]
- Patellofemoral joint issues (1.5% to 58%) 
- Patellar fracture (rare)
In short-term follow-up studies, loss of knee extension of about 5° was greater in the BPTB group than in the hamstring group , but became comparable in 15-year follow-up studies.  A significant increase in osteoarthritis – defined as moderate to severe joint space narrowing – was observed in BPTB patients compared with hamstring graft patients in a minimum 5-year follow-up period.  BPTB graft does not result in patellar tendon shortening when combined with an early aggressive rehabilitation program. 
The assessment of postoperative pain after ACL reconstruction suggests a difference between hamstring and BPTB groups, with BPTB graft patients having decreased satisfaction with their pain management.  Patients should be informed about pain when deciding on a graft. (41)
A recent large Scandinavian registry study reported a higher risk of graft failure with hamstring graft than with BPTB graft,  and a Norwegian study indicated that patients with hamstring grafts had twice the risk of revision compared with patients with patellar tendon grafts at 5 years of follow-up.  Other meta-analyses [9,12] found no significant differences between the 2 groups in terms of graft failure. In general, the difference in graft failure rates is age-dependent across all studies, [19,39,43] with soccer players, adolescents, and high school and college athletes having an increased risk of revision surgery after ACL reconstruction.
Patients with BPTB graft reconstructions are more likely to have statically stable knees, as measured by Lachman and pivot shift tests, than patients with hamstring graft reconstructions.  A higher proportion of BPTB graft patients participate in sports on a weekly basis than hamstring graft patients at 15 years after surgery: 73% versus 48%, respectively. 
In addition, a recent study in a subpopulation of young female patients showed significantly fewer subsequent procedures and a lower rate of graft failures in the BPTB group than in the hamstring group, as well as no difference in subjective functional outcomes.  Given that the optimal graft choice is patient-specific, the use of BPTB autograft in young active female patient is recommended, although the assertion of a more rapid return to sports with BPTB graft remains questionable.
Quadriceps Tendon Graft
The quadriceps tendon is the least studied autograft for ACL reconstruction, and although interest in its use seems to be increasing, only 1% of orthopaedic surgeons consider the quadriceps tendon for either primary ACL reconstruction or for revision surgery.  Marshall et al  initially described the use of the quadriceps tendon for ACL reconstruction in 1979, but favorable results were not described until the 1990s. [60-62]
Despite a lack of comprehensive evaluation about biomechanical characteristics, recent studies have shown excellent clinical results and low morbidity with use of the quadriceps tendon, even when harvested as a free tissue graft without a bone plug. [63,64] The graft can be harvested through:
- A longitudinal incision along the quadriceps tendon
- 2 small incisions just proximal to the patellar insertion and at the level of myotendinous junction
- A transversal incision 2 cm proximal to the proximal pole of the patella
The quadriceps tendon graft can be used with or without bone plugs, and it can be harvested from either side of the quadriceps tendon. No significant difference was noted in cadaveric specimens with regard to tendon thickness or the development of a more robust tendon when harvested from the medial or lateral aspect of the insertion.  In addition, despite the variability in quadriceps tendon morphology, a graft of consistent length (7 to 8 cm), depth (6 to 7 mm), and width (9 to 10 mm) can be harvested with careful surgical technique without violation of the suprapatellar pouch. 
Biomechanical and cadaveric studies have found that the CSA of the native ACL is 44 mm2. The CSA for grafts are:
- Hamstring tendon, 53 mm2
- Patellar tendon, 35 mm2
- Quadriceps tendon, 62 mm2
In addition, the native ACL has an ultimate load to failure of 1,725 to 2,160 N. The load to failure is higher in all autografts:
- Hamstring tendon, 4,090 N
- Patellar tendon, 2,977 N
- Quadriceps tendon, 2,352 N
On this basis, the quadriceps tendon provides a thicker graft than other autograft options with an adequate load to failure in cadaveric models. [66, 67] In addition to the mechanical features, other potential advantages of using this graft include:
- Easier harvest compared with the hamstring and patellar tendons
- Reduced morbidity, as harvesting the quadriceps tendon avoids the infrapatellar branch of the saphenous nerve and can be achieved even without bone block
- Ability to choose the length of the graft
The main weakness compared with patellar tendon graft is the fact that the quadriceps tendon graft has a bone block on only 1 end. 
The possible complications of using this graft include:
- Anterior knee pain
- Quadriceps weakness
- Patellar fracture
- Decreased range of motion
Furthermore, extensive bleeding may occur, possibly leading to hematoma, if the quadriceps muscle is significantly violated, especially at the lateral side where the perforating vessels are located. A full-thickness harvest can also cause an anterior hematoma due to extravasation of articular bleeding through the tendon’s defect.
Although uncommon, retraction of the rectus femoris muscle may occur after full- or partial-thickness graft harvest. [65,69]
Quadriceps tendon autografts generally have lower morbidity and similar complication rates when compared with patellar tendon autografts. Biomechanical evaluation has demonstrated that harvesting the central quadriceps tendon leaves a stronger extensor mechanism than after harvest of a patellar tendon graft. 
Most comparative studies showed no difference between quadriceps tendon grafts and other grafts with regard to clinical results, arthrometric testing, Lachman testing, or pivot shift testing. Previous studies have shown that the percentage of patients with normal Lachman and pivot shift tests is 76% to 100% and 81% to 100%, respectively, following a patella tendon graft and 64% to 100% and 72% to 100%, respectively, following a hamstring graft. 
Studies focused on quadriceps tendon graft showed that 81% to 95% of patients have a normal Lachman test and 80% to 95% have a normal pivot shift test following the reconstruction.  In addition, functional outcomes after ACL reconstruction with a quadriceps tendon graft are comparable to outcomes with other autograft choices, with most knees classified as normal or nearly normal on IKDC assessment. [72,73]
Although the data are not as extensive as for patellar tendon or hamstring tendon grafts, the quadriceps tendon graft is a good alternative due to its mechanical characteristics and unquestioned advantages.
The past 20 years has seen an increase in the use of allografts in ACL reconstruction due to:
- Lack of harvest morbidity
- Less trauma and a quicker surgery
- Decreased postoperative pain
- Easier and early rehabilitation
- Lack of limit to the size of the graft
- The usefulness of allograft for revision surgery
Many potential allograft sources have been biomechanically tested and have produced good results. Pearsall et al  found that the failure loads for tibialis anterior, tibialis posterior, doubled semitendinosus and gracilis, and peroneus longus grafts equaled or exceeded all described ACL autograft sources.  Cole et al  indicated that the extra cost of the allograft tissue is offset by savings in other areas of hospital care, such as operating room time, postoperative observation, and anesthetics and analgesics. 
There are certain risks associated with the use of allografts: 
- Disease transmission
- Immune response against the donor tissue
- Delayed incorporation
- Bone tunnel enlargement
- Alteration of mechanical properties secondary to sterilization and preparation of the graft, which may affect long-term results and rupture rates
Recent papers have shown that fresh frozen, non-irradiated allografts have similar re-tear risk as autografts. In addition, allografts irradiated with higher doses (>2.5 mRad) and secondary sterilized grafts fail at high rates and lose biomechanical properties and graft strength. [49-51]
The biologic incorporation phase has been studied in animal and human models. Jackson et al  demonstrated that compared with autograft, use of allograft resulted in:
- Slower rate of biologic incorporation
- Prolonged inflammatory response
- Greater decrease in implantation structural properties
- Delayed revascularization and recellularization
These findings have also been obtained using contrast-enhanced MRI studies. 
Delayed healing of allograft is also suggested by greater bone tunnel enlargement 1 year after allograft ACL reconstruction compared with autograft reconstruction. Fahey et al  demonstrated an average tunnel enlargement of 1.2 mm for BPTB allograft compared with 0.26 mm for BPTB autograft. The difference appeared to be related to host immunogenicity. 
The failure rate of allografts in long-term follow-up studies is higher than for autograft. In a recent review, Wasserstein et al  reported an allograft failure rate of 25% at 24 to 51 months after reconstruction, compared with 9.5% to 9.8% for autograft. The failure rates for low-dose irradiated grafts versus non-irradiated grafts was 31% and 19.5%, respectively. 
A meta-analysis by Prodromos et al  reported a 5% failure rate for autografts compared with 14% for allografts. Kaeding et al  found that patients with an allograft ACL reconstruction were 4 times more likely to tear the graft than those who had an autograft reconstruction. Many underpowered studies have reported a similar risk of failure for BPTB allograft and autograft. In particular, the highest risk of allograft ACL re-tear was found in younger and highly active athletes. 
It is very difficult to compare the PROMs of autografts and allograft because of the small number of studies reporting statistically significant outcomes.  Allograft ACL reconstruction should be performed with caution in the younger and active patient population. The potential for disease transmission, immune reactions, re-rupture, and poor long-term results, as well as the lack of comparison studies, has tempered the enthusiasm about using these graft in primary ACL reconstruction.
Intuitively, the use of autograft for the reconstruction of a torn ACL remains the ideal option, with reliable long-term results. However, donor-site morbidity remains a drawback. The use of allograft leads to discussion of the risk of possible disease transmission, increased number of failures, increased costs, and delayed incorporation of the graft.
A synthetic material for reconstruction of the ACL, therefore, would appear to be a desirable alternative. Synthetic materials have been widely utilized for many years in many surgical areas.  Despite initial enthusiasm about using them, synthetic ligaments were associated with poor short-term results, and by the early 1990s, a number of devices were withdrawn from the market. [75,76]
Since 2003, second-generation devices with greater safety and efficacy have been available and have lower reported rates of failure, revision, and sterile effusion/synovitis compared with older devices. [77-79] To date, however, the literature is limited primarily to studies with low-levels evidence.  Further randomized controlled trials and long-term studies will be needed to validate the synthetic device for ACL reconstruction.
Living Donor Allograft
The number of ACL reconstructions in patients under age 16 has more than tripled over the past decade. Several authors have shown a high risk of further ACL injury after reconstruction in patients younger than age 16, with re-rupture rates as high as 17%. [80-82] Graft diameter is known to be associated with early graft failure, and given that the diameter of soft tissue is directly related to height and weight, [83,84] sourcing an autograft with a suitable diameter in a child can be a challenge (85).
Patellar and quadriceps tendon grafts are not recommended in patients younger than age 16. Allografts can be an alternative; however, disease transmission, delayed graft incorporation, potential immune reactions, increased postoperative traumatic rupture rate, and graft preparation problems (including weakened irradiated allografts, bone tunnel enlargement, and graft cost) have all been reported in this young patient population. [86, 87]
Characteristics of the ideal graft for children include the following: 
- Biologically active
- Appropriate size for the patient’s knee
- Will not cause donor site morbidity
- Retains the neuromuscular structures of the knee; hamstring muscles are known to have a protective effect on the ACL because they counteract anterior shear forces by co-contracting during knee extension
Related living donor allografts for ACL reconstruction have the potential to fulfill these criteria.  Goddard et al  and Tállay et al  have described the procedure for this type of allograft for primary reconstruction and revision surgery in children. They recommend harvesting the hamstring from the left limb to allow the donor to drive a car with automatic transmission using their un-operated right limb as soon as possible. The size of the child’s knee and the intercondylar space will help to determine whether the surgeon should harvest only the semitendinous tendon or the semitendinosus and gracilis tendons from the donor to ensure a graft with an adequate diameter while also avoiding graft impingement.
In addition, the child and donor should be screened for human immunodeficiency virus, hepatitis C, human papillomavirus, and cytomegalovirus, and all children should undergo histocompatibility testing, including Rh status. Rh-negative female patients should receive an appropriate dose of Rh immunoglobulin on induction of anesthesia to prevent Rh sensitization if Rh incompatibility is present. 
To the authors’ knowledge, the literature contains only 1 case series on this procedure. It shows good result with regard to clinical outcomes, arthrometric testing, and clinical tests, with favorable results at 2 years of follow-up. The incidence of ACL graft ruptures is only 6% in this case series. 
From an economic standpoint, the use of living donor allograft seems to be less expensive than using a conventional allograft for the ACL reconstruction and should be considered a viable option in children who need ACL reconstruction.
A review of the recent literature indicates that autograft is superior to allograft with respect to failure rates and long-term outcomes, particularly in younger and active patients. The major risk factors for ACL re-tear are younger age and high activity level regardless of graft choice. Future high-level studies are needed to determine any differences between hamstring tendon, BPTB, and quadriceps tendon autografts. Randomized controlled trials and long-term studies are also needed to validate the use of synthetic devices. In children, the use of living donor allografts should be considered as a viable option.
Alberto Castelli, MD; Enrico Ferranti, MD; Eugenio Jannelli, MD; Giacomo Zanon, MD; and Francesco Benazzo, MD, are from IRCCS Policlinico San Matteo, Orthopaedics and Traumatology Department, University of Pavia, Pavia, Italy. Simone Perelli, MD, is from the Knee and Arthroscopy Unit at ICATME, Hospital Universitari Dexeus, Barcelona, Spain.
The authors have no disclosures relevant to this article.
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