Injuries to the anterior cruciate ligament (ACL) are common with a reported case load of over 200,000 reconstructions performed in the United States annually [1]. Reconstruction of the ligament is frequently performed to restore anterolateral stability to the knee in order to prevent further intraarticular damage from repeated pivoting episodes and to return athletes to competitive play [2, 3]. Typical choices for grafts that are used for reconstruction purposes are autografts which include bone-patellar tendon-bone, hamstring, and quadriceps tendons and allografts which come from a variety of sources. Examples of allograft materials are patellar tendon (with and without bone blocks), Achilles tendon, tibialis anterior, tibialis posterior, and quadriceps tendons.

Traditionally, allograft tissue has been favored for ACL reconstruction because it allowed for a much more rapid and easier procedure. In addition, due to the absence of donor site morbidity that is inherent with the use of autograft materials, the patient is likely to experience much less pain subsequent to surgery which may in turn accelerate progress during rehabilitation. However, a majority of studies investigating the long-term viability of allograft tissue have demonstrated a significant failure rate in the younger population [4, 5]. Evidence from basic science investigations have revealed that allografts undergo a similar “ligamentization” process as autografts when implanted into the knee. However, the replacement of the donor tissue with host synovial cells is much slower when compared with reconstructions using autografts, which may help to explain the fact that allografts typically demonstrate inferior biomechanical properties as autografts during the healing phase [6]. These findings have limited the use of allografts in this patient population, and most surgeons now prefer to utilize allografts in the older, less active population among whom the risk of graft rupture is comparatively less.

Despite these concerns, allografts remain a popular choice for ACL reconstruction in the proper setting. The following chapter will detail the common indications and methods of processing for allografts and review the current literature regarding the outcomes related to their use.

The prevailing concept that allograft tissue is significantly weaker than autograft tissue has led to a decrease in the use of this graft choice in the younger, athletic population. Nevertheless, the choice of allograft may be considered in the setting of primary ACL reconstruction. Older patients electing to proceed with ACL reconstruction are more likely to receive allografts as it is generally believed that these patients will progress more slowly through the rehabilitation phases, thereby reducing the stress on the implanted graft and allowing for additional time for healing. This trend is supported by the 2013 AOSSM report on allograft usage in ACL surgery, which revealed that the allocation of allografts by surgeons is predominantly aimed at patients in the 35–40 year range [7].

The choice to utilize allografts for the purpose of reconstruction may also be influenced by settings in which there is insufficient autograft tissue for harvest, such as in cases that require the surgeon to address multiple injured ligaments, cases where the intended autograft harvested is too small for use, or in cases of revision ACL reconstruction. When addressing multiligamentous knee injuries, the need for additional collagen often makes the use of autograft tissue impractical given the significant morbidity inherent in extracting graft material as well as the scarcity of available tissue. Multiligamentous knee injuries may include ruptures to the posterior cruciate ligament and posterolateral corner. While repair of the posterolateral corner remains an accepted form of treatment during acute intervention, the stability of direct repair has been questioned, and evidence has suggested that more reliable stability can be obtained by augmentation with allograft [8, 9]. In such cases, to reduce the morbidity to the knee that has already experienced significant injury and to reduce overall surgical time, the surgeon may be more inclined to reconstruct the ACL with allograft tissue.

Another common scenario that may require allograft use is under circumstances when the intended autograft tissue is estimated to be too small to effectively reconstruct the ACL. This is often encountered during the use of hamstring autografts. Past studies have noted that the threshold diameter for the hamstring graft that is associated with lower rerupture rates is approximately 8 mm [10, 11]. Not infrequently, the diameter of the hamstrings may be smaller than this threshold. For this reason, allograft material may be combined with the hamstring autograft to create a composite graft. This technique can significantly enhance the diameter of the graft above the 8 mm threshold, increasing the stability of the soft tissue reconstruction.

Finally, it is common for consideration to be given to allograft material when performing revision ACL reconstruction. Due to tunnel dilation that may occur as a consequence of the primary ACL reconstruction, the tissue available for autograft may be insufficient to accommodate the larger tunnel diameter, particularly if the intended graft is bone-patellar-tendon-bone or hamstring tendon. In addition, if the primary surgery was performed using autograft material, the preferred autograft may not be present for use during the revision surgery. Allografts provide a solution to both problems by providing the surgeon with a variety of graft types with a wide range of dimensions to fit bone tunnels that have expanded since the index operation. The use of allografts also affords flexibility in terms of graft size during revision cases, with larger allografts granting the advantage of favorable time-zero strength when stability of the graft is a concern. Because of these properties intrinsic to allograft materials, studies have supported the idea that a greater proportion of surgeons do elect to utilize this type of graft for revision ACL reconstruction. According to a report by the Multicenter ACL Revision Study group, approximately 54 % of surgeons participating in the study chose to perform a revision ACL reconstruction with an allograft compared to 27 % of surgeons who used allograft for primary ACL reconstruction [12].

The handling of allogeneic material is overseen by the combined effort of both the organ procurement organizations (OPOs) and the tissue banks. In North America a nationwide network of OPOs acts as central coordinating agency for tissue donation. The OPOs, as members of the Organ Procurement Transplant Network, are responsible for tissue and organ recovery and distribution within a predefined service area. After evaluation and screening for potential donors, the OPOs arrange the surgical removal of the donated tissue. The tissue banks on the other hand are primarily responsible for the tissue procurement process. The tissue banks follow the quality instructions and standards of the Food and Drug Administration (FDA) and American Association of Tissue Banks (AATB). A trained donor coordinator obtains consent from the patient or the family and provides information how the donated tissue is going to be used [13].

Great care is taken to ensure that maximum sterility of grafts is achieved once they are considered ready for use. Most tissue banks mandate that grafts be harvested no more than 24 hours from death for refrigerated grafts and no more than 12 hours from death for cadavers stored at room temperature [14]. Prior to harvest, the tissue donor must be screened for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. Frequently, the tissues are aseptically harvested in the operating room or morgue. However, the tissue extracted in this manner should not be considered sterile, since aseptic processing minimizes but does not obviate tissue contamination [13, 15]. The grafts are then passed through a process of decontamination.

Understanding the phases of procurement requires an awareness of the meaning behind disinfection, which is interpreted as the elimination of contamination, and sterilization, which is interpreted as the total extermination of all life forms [16]. The FDA currently does not require sterilization of medically appropriate grafts. In fact, a sterility assurance level (SAL) of 10⁻⁶ is recommended during the decontamination process to maximally reduce the risk of disease transmission. This threshold level is understood to mean that the risk that a microorganism might survive the decontamination process is less than 1 in 1,000,000.

In order to attain this quality of sterilization, different mechanical and chemical processes have been developed over the years. The use of gaseous ethylene oxide as sterilizing agent has been abandoned due to its immunogenic effects, reported adverse events, and poor tissue penetration [13]. In general, initial graft treatment typically consists of chemical decontamination with a series of antibiotic solutions. This method however does not lead to sterilization of the graft. A very common method of mechanical sterilization is the use of ionizing radiation (gamma irradiation). To eliminate HIV an irradiation dose of 35–40 kGy is required. However, this dosage leads to collagen breakdown with significant deterioration of the biomechanical and structural properties of the processed graft properties [17]. Therefore, many tissue banks use lower irradiation doses between 10 and 25 kGy [18]. However, these irradiation doses are effective against bacteria but less effective against viruses [13]. Because of the disadvantages of both mechanical and chemical treatments, modern methods for graft decontamination elect to utilize a hybrid approach to achieve a level close to sterilization as possible. The combination of both chemical and mechanical processing methods (i.e., BioCleanse®, Allowash®) showed initially promising results [19], but a cohort study with more than 5,000 participants found a significantly increased risk of graft failure and subsequent revision surgery when the graft was treated with BioCleanse® [20].

The use of nonirradiated allografts is becoming more popular due to their superior biomechanical and biological properties. Many recent studies have demonstrated the clinical effectiveness of nonirradiated allografts, particularly in reducing the incidence of graft rupture [21, 22]. One example is the use of freeze-dried grafts (lyophilized tissue). During the lyophilization process, the moisture content of the graft is reduced to less than 5 % and needs therefore to be rehydrated before use. In the recent years, fresh-frozen allografts have been most commonly used. After sterile tissue harvesting and culturing, the graft is frozen while serologic tests performed. Before packaging the graft is soaked in an antibiotic solution and can be stored at −80 °C for 3–5 years [16, 23].

It is clear that the procurement process plays a vital role in the overall clinical performance of ACL reconstruction with allograft materials. However, a majority of orthopedic surgeons who perform this procedure remain unaware of the graft processing methods for the allografts they utilize. A survey of 236 hospitals in the United States reported that only 34 % of orthopedic surgeons performing allograft-related surgeries were familiar with the tissue processing history [24]. In addition, in only 15 % of the facilities surveyed did the orthopedic surgeon directly contribute to the type of allograft selected. This data highlights a significant problem in the use of allografts for surgery, particularly in the case of ACL reconstruction in which the concerns regarding graft longevity may be profoundly influenced by the variability in procurement methods.

There have been many studies comparing the short-term outcomes of ACL reconstruction with autografts and allografts in patients. Early studies were favorable toward the use of allografts. Shino et al. published a study with 84 patients after ACL reconstruction with allografts with an average follow-up of 57 months [25]. The patient population was relatively young with an average age of 22 years old and there was no evidence of immunologic rejection. Subjective and functional outcomes were good with 57 % of patients having “excellent” outcomes, 37 % with “good” outcomes, and only 2 % with “fair” outcomes [25]. Objective physical exams also found that 88 % of patients had satisfactory anterior stability, though 3 % of patients did have a reinjury. Noyes et al., while preferring autografts, also found allografts to be a justifiable substitute since they could find no significant difference in anterior-posterior displacement, patellofemoral crepitus, pain, jumping score, or overall knee rating [26].

Other studies directly compared allografts to autografts. While allografts were rarely shown to perform better than the gold standard autograft, there was evidence to show that outcomes following surgery with each type of graft were comparable. Rihn et al. found no significant differences in average International Knee Documentation Committee (IKDC) subjective knee scores between patients who received irradiated bone-patellar tendon-bone allografts (BTB) and BTB autografts (P = 0.65) [27]. There were also no significant differences in the percentage of patients in each cohort that reported a normal/nearly normal overall IKDC physical examination rating (P = 0.37) or that returned to the same or more strenuous level of sports (P = 0.25) [27].