Allograft Anterior Cruciate Ligament Reconstruction

Chapter 45 Allograft Anterior Cruciate Ligament Reconstruction



Allograft usage in orthopedic operations has increased significantly over the last 2 decades.19 Approximately 20% of the estimated 300,000 anterior cruciate ligament (ACL) reconstructions done annually are performed with an allograft.63 Because of certain drawbacks of autogenous graft ACL reconstruction, allograft usage has gained popularity. There are a variety of allograft options available to the orthopedic surgeon for ligamentous reconstruction operations. Allografts have their own unique risks and disadvantages that the surgeon and patient must consider as part of the informed consent.



Allograft Considerations



Graft Options


ACL reconstruction using autograft patellar tendon was first described by Jones in 1963.40 Now, patellar tendon autograft is considered the gold standard for ACL reconstruction.77 Patellar tendon autograft offers high initial strength, earlier bone-to bone healing, and proven success by a multitude of outcome studies.1,6,16,20,53 However, despite being the gold standard graft choice, there are several disadvantages to autogenous patellar tendon harvest. These include anterior knee pain, patellar shortening, decreased range of motion, longer surgical time, infrapatellar fat pad fibrosis, patellar fracture, and patellar chondrosis.* Dynamic disadvantages of autograft patellar tendon harvest include decreased quadriceps strength, quadriceps inhibition, altered patellar alignment, and decreased active range of motion.36,44,51


Quadrupled hamstring autografts (semitendinosus and gracilis tendon autograft) have been shown to have the highest tensile strength and excellent clinical results. However, disadvantages include decreased knee flexion and hip extension strength, which can be detrimental to athletes who rely on knee flexion strength beyond 90 degrees of flexion (e.g., sprinters, wrestlers, gymnasts, martial arts practitioners).36,74,79 Furthermore, hamstring strength has been shown to be protective of ACL reconstruction by way of the ACL-hamstring reflex arc. Taking the semitendinosus and gracilis tendons results in disruption of this arc and a decrease in the protective effect of the hamstrings on the ACL graft.9


Quadriceps tendon autograft is also being used in some centers for ACL reconstruction. Limited outcome data are available but early studies have suggested equivalent results between quadriceps tendon (with patellar bone plug) autograft and patellar tendon autograft. After a 2-year follow-up, a recent study has found that kneeling pain is significantly less than with a bone-patellar tendon-bone (BPTB) autograft but anterior knee pain in the two groups is similar.45


Because of the potential drawbacks of autograft ACL reconstruction with patellar tendon, hamstring, or quadriceps tendon, allograft ACL reconstruction is increasing in the United States.5,77 Advantages of an allograft include elimination of donor site morbidity, decreased surgical time, smaller incisions, lower incidence of arthrofibrosis, decreased postoperative pain, no loss of donor graft function, faster subjective recovery time, and predictable graft sizes.19,27,41 Allograft options include patellar tendon, hamstring, anterior tibialis, posterior tibialis, Achilles, and fascia lata. However, allograft drawbacks also exist, such as disease transmission, slower incorporation, possible immunologic reaction, finite supply, tunnel expansion, inferior biomechanical strength, possibly increased failure rate, and cost.31,33,65,71,73



Graft Procurement and Sterilization


There are over 150 individual tissue banks that provide allograft for surgical use. Most of these tissue banks are members of the American Association of Tissue Banks (AATB). Beginning in May 2005, federal legislation was passed mandating that all United States tissue banks be subject to the U.S. Food and Drug Association (FDA) “Good Tissue Practice” guidelines. These guidelines specify a minimum standard for tissue procurement, as well as testing and processing, require periodic inspections of tissue bank facilities, and necessitate reporting adverse events to the FDA.19,77


Graft procurement begins with donor screening to eliminate donors who are at high risk for transmitting communicable diseases. This involves screening prior to death and evaluating cause of death. High-risk donors are eliminated; these include those who have a known communicable disease, show active signs of infection despite not having a diagnosis, or whose lifestyle places them at high risk for infection. Physical examination is the next step to assess the potential donor for high-risk behavior (e.g., needle marks, skin findings). Third, blood tests and tissue cultures are taken from the potential donor to rule out an otherwise undetermined communicable disease. Required serologic tests include human immunodeficiency virus (HIV) types 1 and 2, hepatitis B, hepatitis C, and syphilis. The AATB-affiliated tissue banks also test donors for human T-lymphotropic virus (HTLV) types 1 and 2. Certain tissue banks may accept positive bacterial cultures, relying on the sterilization process to eliminate the infection. Tissue banks that are part of the AATB require destruction of all tissue that demonstrates positive cultures for Clostridia or group A streptococcus.19 Once these criteria are met and passed, the graft is suitable for procurement in the standard sterile surgical fashion. Each tissue bank has a specific time window for acceptable retrieval of graft tissue. Once obtained, the graft is placed in an antimicrobial solution and taken to the sterilization plant.


Sterilization is performed via two techniques, tissue irradiation and chemical processing. It has been found that high levels of irradiation (>25 kGy) can reliably inactivate HIV and spores. However, these same high levels of irradiation can be detrimental to the biomechanical properties of the graft itself.43,71,77 Thus, most tissue banks use lower dose irradiation, which inactivates most organisms but does not alter the strength of the graft. Low-dose radiation may not inactivate viruses such as HIV.76 Various tissue banks will use different radiation dosages and some banks have abandoned irradiating as a sterilization technique because of adverse effects on graft biomechanics. Chemical processing involves a succession of cleansing, disinfection, and rinsing of the tissue to remove viable cells, lipids, and microorganisms. Penetration into the deepest parts of the tissue is the primary challenge in chemical sterilization. Various tissue banks have their proprietary chemical cleansing solutions. Tissue “sterility” (sterility assurance level) is defined by the tissue banking industry as P < .000001 that a viable microbe is present in tissue after having undergone the sterilization process. Once the sterilization process is complete, the graft is then frozen at −70° C to −80° C until surgery. Deep freezing has been shown to decrease the risk of graft rejection by causing cell necrosis and loss of immunogenicity.27 Freezing of allograft tissue has led to variable results in biomechanical properties, with some studies suggesting no difference, whereas others demonstrating that freezing is detrimental to graft strength.54,60 Deep freezing does not destroy HIV or the hepatitis C virus. Tissue irradiation, chemical processing, and deep freezing have been found in some studies to result in decreased graft biomechanical strength. Because the procurement and sterilization protocols of tissue banks can vary, the surgeon and hospital should be well aware of the quality and techniques of tissue processing of the company that they choose to use as their source of graft tissue.



Infection


The risk of disease transmission is an important factor when weighing the options of allograft versus autograft ACL reconstruction. Possible infectious agents include HIV, hepatitis B, hepatitis C, HTLV, syphilis, aerobic bacteria, and anaerobic bacteria. With tissue banks adopting varying procedures on graft sterilization, the risk of disease transmission is also variable. The risk of HIV infection has ranged in the literature from 1 to 400,000 to 8,000,000, with a commonly quoted figure of 1 to 1,600,000.5,11,12,19 The risk of hepatitis B and C virus infection has consistently been shown to be higher than that of HIV transmission. Bacterial infection is also a concern with regard to disease transmission with Clostridium spp. (a spore-forming anaerobe) being a common pathogen. In a Centers for Disease Control and Prevention (CDC) study performed in 2002, 26 cases (18 used for ACL reconstruction) of allograft-associated bacterial infections were identified in approximately 1 million transplanted allografts. Half of these were found to be caused by Clostridium spp., with one death.13 In another CDC study,42 published in 2004, 70 cases of allograft-associated infection were reported; it was found that since 1995, 6 were caused by hepatitis C and none by HIV. Of these patients, 14 were found to have Clostridium infections.


Routine culture of allografts prior to implantation has yielded 4.8% to 9.7% positive cultures for bacterial organisms, but no clinical infection was correlated with these positive culture results.14,30 Thus far, routine preimplantation cultures have not been recommended. Because tissue banks differ in their methods of sterilization, the surgeon should be familiar and comfortable with the tissue processing of the bank selected and be able to discuss possible infection transmission risks with patients as part of the informed consent.



Graft Biology


Allograft incorporation and healing is critical to the success of ACL reconstruction. One commonly cited disadvantage of allograft usage for ACL reconstruction is slower and less extensive incorporation compared with autograft ACL reconstruction.24 Allograft versus autograft ACL reconstruction has been compared from histologic, biomechanical, and radiographic perspectives. A recent sheep study72 comparing native ACL, reconstructed soft tissue autograft ACL, and reconstructed soft tissue allograft ACL has suggested that allograft demonstrated delayed remodeling histologically at 6 and 12 weeks postoperatively. However, at 52 weeks, the differences were less apparent. Biomechanically, allografts at 52 weeks demonstrated statistically significant anteroposterior laxity compared with autografts; this was not present at 6 and 12 weeks. Allograft healing was improved in a rabbit histologic study when the fresh-frozen Achilles allografts were coated with mesenchymal stem cells compared with controls (Achilles allograft only).75 Radiographically, BPTB allografts were found to have less revascularization by contrast-enhanced magnetic resonance imaging (MRI) at 1, 4, 6, and 12 months after surgery, but were found to equalize at 18 months postoperatively. The authors suggested that revascularization is slower in BPTB allografts compared with BPTB autografts.58 However, computed tomography (CT) imaging of BPTB bone plugs at 1 week, 2 months, and 5 months did not show a significant difference in bony incorporation of BPTB allograft versus BPTB autograft.50


For allograft ACL reconstruction to be successful, the graft must heal adequately in the bone tunnel. The intra-articular portion of the allograft must undergo the process of ligamentization in which the graft remodels to resemble the histology of a native ligament more closely.31


Soft tissue allografts must undergo tendon to bone tunnel healing. The native ACL insertion site is an example of direct insertion from tendon to bone. Four distinct histologically appreciable zones comprise this insertion site—tendon, unmineralized fibrocartilage, mineralized fibrocartilage, and finally bone. With soft tissue ACL reconstruction, this direct insertion site is not replicated. Rather, indirect insertion is relied on for soft tissue graft healing within the bone tunnel. Indirect insertion is naturally exemplified by other ligaments, such as the medial collateral ligament (MCL), which broadly inserts along the surface of the bone through fibers that travel obliquely from the long axis of the ligament to the long axis of the bone. These fibers, known as Sharpey’s fibers, are also seen histologically in ACL reconstruction with tendon grafts and correlate with the biomechanical properties of the graft insertion site.28,31,70


A number of strategies have been used to improve the strength and healing of the soft tissue graft within the bone tunnel. Creating a longer tunnel has been shown to increase the strength of the graft-tunnel interface, presumably by increasing the amount of contact between the graft and the bone.81 Impregnating the graft with mesenchymal stem cells, as suggested earlier, has shown superior healing as well as more normal tendon to bone insertion histology.49,62,75 The application of bone morphogenic proteins to the graft has also been shown to increase bone formation around the graft as well as graft pull-out strength.55 Inhibition of osteoclast activity has been investigated with the use of osteoprotegerin (OPG). OPG-treated grafts in rabbits demonstrated greater bone formation and smaller sized bone tunnels around the graft.25 Inhibiting degrading matrix metalloproteinases (MMPs) in rabbit allograft ACL reconstruction has shown more Sharpey’s fibers and a stronger load to failure.21 The primary healing response after graft implantation involves the arrival of inflammatory cells facilitated by cyclooxygenase-2 (COX-2). Studies have shown that avoiding anti-inflammatory medications such as COX-2 inhibitors allows the primary healing phase to proceed without chemical interruption. Some have cautioned against the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent inhibition of the primary healing response.18,31,61


Compared with soft tissue grafts, which require soft tissue to bone healing within the osseous tunnel, BPTB grafts require bone to bone healing. This bone to bone healing is widely accepted as the strongest form of healing for ACL reconstruction. Histologic studies have demonstrated that the implanted bone plug demonstrates initial osteonecrosis and hypocellularity followed by revascularization, fibroblast invasion, and collagen synthesis, with subsequent rapid incorporation of the plug by surrounding bone.22,39,64,80 These changes have been found to be similar in autograft versus allograft BPTB healing. Within 3 weeks, histologic incorporation is visible, but still fragile. At 3 weeks after implantation, the weakest point of a BPTB autograft remains the graft-tunnel interface. However, at 6 weeks, this interface has healed so that the site of graft failure is at the patellar tendon insertion into the bone plug.31 Although some studies evaluating timing of incorporation have suggested no significant difference between autograft and allograft bone plugs, others have shown that allograft bone plugs require a longer time to incorporate and central portions of the plug may not incorporate at long-term evaluation.37,38,52 Healing of the bone plug likely occurs from the end of the tunnel furthest from the influences of degradative enzymes in the synovial fluid.8


Ligamentization of the graft is the phase of graft incorporation in which the intra-articular portion of the graft undergoes changes that more closely resemble the histologic properties of a native ligament. Whether autograft or allograft, this process takes several months and undergoes a series of steps.31,38 Similar to the initial events of bone plug incorporation, the ligamentous portion also undergoes an initial phase of avascular necrosis and acellularity. Despite being devoid of cells, the graft maintains its collagenous structure, which serves as a scaffold for subsequent steps—cellular repopulation, revascularization, and ligament maturation.3,4 The timing of these steps, outlined in a rabbit model, has demonstrated that at 2 weeks, necrosis of the graft begins. At 4 weeks, the graft is completely devoid of cellularity but the collagen scaffold remains intact. At 12 weeks, vascular proliferation and cellular repopulation are appreciated. At 6 months, the cellularity of the graft is similar to that of a native ligament. Finally, at 9 months, the graft is mature and histologically similar to a native ACL.61 In humans, surface blood flow studies have suggested that after an initial period of increased flow, ACL allografts demonstrate normal surface blood flow at 18 months, implying the end of graft remodeling.71



Results of Allograft Anterior Cruciate Ligament Reconstruction


Autograft ACL reconstruction has generally been accepted as the gold standard for ACL graft choice, providing optimal graft strength and healing. Nonetheless, the use of allograft ACL reconstruction is increasing because of disadvantages specific to autogenous graft harvest. There have been several studies comparing subjective and objective outcomes of allograft versus autograft ACL reconstruction, with the best of these being prospective cohort studies. Randomization of graft is difficult because the patient must be informed of graft type and the inherent and specific advantages and drawbacks. Recent relevant studies are briefly reviewed in this section.


One randomized study in the literature by Sun and colleagues76 have compared three groups: BPTB autograft, irradiated (2.5 Mrad) BPTB allograft, and nonirradiated BPTB allograft. In ths study, 99 patients were randomized to one of these three groups on the day of surgery with almost evenly sized comparison groups (34, 33, and 32 patients). At 31 months postoperatively, these patients were evaluated subjectively and objectively. No statistically significant difference was found among the three groups with regard to International Knee Documentation Committee (IKDC) functional and subjective evaluations, but a trend toward inferior outcome scores was noted in the irradiated group. However, statistically significant differences were found for stability testing in the irradiated allograft group compared with the other two groups. KT-2000 testing found that only 31.3% of irradiated patients had less than a 3-mm side to side difference compared with 87.8% in the autograft group and 85.3% in the nonirradiated allograft group. Furthermore, graft failure in the irradiated group occurred in 34.4% of patients compared with 6.1% in the autograft group and 8.8% in the nonirradiated allograft group. The authors concluded that they do not recommend the use of irradiated allograft tissue, but nonirradiated allograft BPTB provides similar results to autogenous BPTB graft. The same group published another prospective randomized study comparing autograft BPTB with nonirradiated allograft BPTB and evaluated 5.6-year follow-up data.78 No statistically significant difference was found except shorter surgical time and longer postoperative fever for the allograft group (80 patients, average age 32.8 years) compared with the autograft group (76 patients, average age 31.7 years). It was concluded that nonirradiated allograft is a reasonable alternative to autograft use for ACL reconstruction.


In contrast, Rihn and associates69 have prospectively compared 39 irradiated (2.5 Mrad) BPTB allograft ACL reconstructions with 63 BPTB autograft ACL reconstructions, with an average follow-up of 50.4 months. It was found that both cohorts have similar clinical outcomes, as measured by IKDC scores and KT-1000 translation. It was concluded that irradiated BPTB allograft has results similar to those of BPTB autograft ACL reconstruction. Two other prospective BPTB allograft versus autograft prospective cohort studies have found equivalent functional outcomes, one at 25.6-month and another at 47.1-month follow-up.7,47


Believing that the prospective trials in the literature comparing BPTB autograft with BPTB allograft ACL reconstruction were underpowered, Krych and coworkers46 performed a meta-analysis of six prospective trials to compare the two groups. They compiled a group of 256 patients who underwent BPTB autograft ACL reconstruction and 278 who underwent BPTB allograft ACL reconstruction. Their analysis demonstrated that those in the allograft group were more likely to rerupture in comparison with those in the autograft group (odds ratio [OR], 5.03; P = 0.01) and more likely to have a hop test less than 90% of the contralateral nonoperated limb (OR, 5.66; P < .01). However, when irradiated and chemically processed grafts were excluded, there was no difference between the allograft and autograft groups with regard to graft rerupture, rate of reoperation, IKDC normal and near-normal scores, Lachman, pivot shift, and hop tests, patellar crepitus, or return to sport.


One recent study has prospectively evaluated autograft quadrupled hamstring tendon versus allograft quadrupled hamstring tendon without complete randomization.26 A cohort of 37 autograft hamstring ACL reconstructions was compared with 47 allograft BPTB patients. No difference was found in Tegner, Lysholm, KT-1000, or IKDC scores at follow-up periods of 52 months (autograft cohort) and 48 months (allograft cohort).


Soft tissue graft irradiation was compared in a study evaluating irradiated (2 to 2.5 Mrad) versus nonirradiated Achilles allograft in regard to early failure.68 With at least 6-month follow-up, the nonirradiated group had a 1/42 (2.4%) graft failure rate compared with 11/33 (33%) failure rate in the irradiated Achilles allograft group (P < .01). This significantly higher failure rate led the authors to cease using irradiated allografts for ACL reconstruction.


A noncomparative long-term outcome study evaluated 61 patients with a mean age of 20.9 years who underwent free tendon allograft ACL reconstruction.59 Mean long-term follow-up of 11.5 years was compared with 2-year postoperative data in the same group of patients; of these, 87% of patients maintained a negative Lachman test result whereas 85% of patients maintained a negative pivot shift test result. Mean KT-2000 laxity measurements were a 1.6-mm side to side difference at long-term follow-up and no more than 3 mm in 92% of patients. All patients except one assessed their knee as normal or near-normal by IKDC score. It was concluded that free tendon allograft ACL reconstruction affords knee stability for the long term. Another long-term follow-up study also found good clinical results (IKDC, Lysholm, Tegner, one-leg hop test) in 55 patients followed for a mean of 10 years after having undergone free tendon allograft ACL reconstruction.2 Harreld and colleagues34 have described self-reported patient outcomes at short-term (mean, 2.8 years) and long-term (mean, 7.8 years) follow-up after ACL allograft (mix of BPTB and free tendon allograft) reconstruction. No differences were found in the short-term group compared with the long-term group with regard to IKDC subjective evaluation or Knee Outcome Survey Activities of Daily Living Scale (KOS-ADLS) scores. However, there was a statistically significant decrease in the KOS-ADLS score in the long-term cohort, suggesting that over the long term, patients have a decreased perception of sporting activity knee function.

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Aug 26, 2016 | Posted by in ORTHOPEDIC | Comments Off on Allograft Anterior Cruciate Ligament Reconstruction

Full access? Get Clinical Tree

Get Clinical Tree app for offline access