Osteochondral Allograft Transplantation in the Knee
The concept of treating articular cartilage diseases with bone and cartilage substitution in the knee has now a history of more than a century, since the first joint transplantation described by Lexer in 1908.1,2 Animal and clinical studies concerning transplantation and immunology were performed in the 1960s, demonstrating that transplanted fresh cadaver cartilage is viable.3–5 In the 1970s, Gross and colleagues began reporting on their experience with osteochondral allograft (OCA) for post-traumatic and periarticular tumor reconstruction.6,7 In the 1980s, Meyers et al first applied this technique to specific chondral and osteochondral diseases such as chondromalacia, osteoarthritis, and osteonecrosis,8 developing the shell-shaped graft. Later in the 1990s, Garrett first reported on the use of allograft plugs for the treatment of osteochondritis dissecans (OCD) of the knee.9 In the past 20 years a large number of basic scientific and clinical studies have been performed by several investigators. These studies and the increasing availability of fresh allografts have led to an increasing popularity of fresh allografts and the inclusion of this procedure as part of the “cartilage repair paradigm” for the treatment of chondral or osteochondral lesions in the knee.10–12
Allograft Recovery, Processing, and Storage
Historically, in North America, fresh OCA procedures were performed at university-based centers that had associated tissue banks, which independently established recovery, processing, and release protocols. Fresh OCAs were typically stored in lactated Ringer solution and transplanted fresh within 1 week after the donor′s death. Under this model ∼ 100 allografts per year were implanted in North America in the 1980s and 1990s. Beginning around 1998, commercially supplied allografts became available in the United States through several tissue banks that established new protocols under the oversight of the Food and Drug Administration. Commercial distribution of grafts required a prolonged storage interval (10 to 45 days) to allow for completion of recovery and testing protocols. This resulted in an increase in the number of allografting procedures performed in the United States to ∼ 2,000 per year.
Allograft tissue recovery is performed within 12 to 24 hours of the donor′s death.13 Suitable donors are generally between 15 and 35 years of age with macroscopically healthy articular cartilage. As the transplantation procedure is based on cartilage substitution, a process that maintains allograft cartilage tissue health during storage is mandatory. Many studies have been performed to identify the ideal storage media and to evaluate the effects of hypothermic storage on chondrocytes and extracellular matrix (ECM).14–19
OCA can be stored frozen, cryopreserved, or fresh. Each of these options affects chondrocyte viability, immunogenicity, and length of time to transplantation. Frozen grafts showed a chondrocyte survivorship of less than 5% because of the freezing process at −80°C.20 As chondrocytes are responsible for maintenance of the ECM, studies have shown that the matrix in these frozen allografts tends to deteriorate over time.21,22 Along with the decreased chondrocyte viability, frozen allo-grafts showed decreased immunogenicity.23
With cryopreservation it is possible to maintain chondrocyte viability during this freezing process by adding glycerol and dime-thyl sulfoxide to the tissue. Theoretically, the addition of these chemicals prevents ice formation within cells. Multiple studies have reported variable results, with chondrocyte survival ranging from 20 to 70%.24–27 Unfortunately, viable cells were found only at the surface of the articular cartilage layer.28 Fresh allografts proved to have the highest rates of chondrocyte viability of the three different methods of storage.19,25,29,30 Fresh grafts are usually placed in tissue culture medium at 4°C (or potentially 37°C). Chondrocyte viability is significantly affected by length of storage, with little effect from storage times less than 1 week.31,32 The time of storage before implantation is a key point. Studies have shown a time-dependent decreased chondrocyte viability and degradation of biomechanical properties of fresh grafts stored for more than 14 days.33–35 Currently the trend of the tissue banks is to hold transplants for a minimum of 14 days, to allow completion of microbiologic and serologic testing before release.36
More recently a new off-the-shelf alternative to classic OCA has been developed and released in the U.S. market: The Chondrofix Osteochondral Allograft (Zimmer, Inc., Warsaw, IN). This product is an OCA consisting of decellularized hyaline cartilage and cancellous bone, recovered by an accredited tissue bank, processed to be sterile and viralinactivated, hydrated, precut, and ready for implantation. The relative advantages include an off-the-shelf availability, sterility, and ease of use, whereas potential limits are availability in sizes only up to 15 mm and the absence of viable cells within the graft. Currently no published peer-reviewed data are available; however, preliminary experience suggests a place for this product in the pool of newer alternatives for chondral and osteochondral repair or replacement.
Biologic Response to Implanted OCA
Intact hyaline cartilage is a relatively immunoprivileged tissue as it is not vascularized and its cellular portion is embedded in the ECM, inaccessible to the host immune system. Conversely, the osseous component of the graft is laden with potentially immunogenic cells and proteins, which can be partially mechanically removed by graft lavage before implantation. Several studies have demonstrated that the osseous portion of the graft is replaced with time by host bone, the process of creeping substitution, which may or may not lead to complete replacement of allograft bone by host bone.13,37,38 In another study, larger grafts (> 10 cm2) were noted to be far more likely to elicit a systemic immune response.39 These studies have led to our practice of transplanting the minimal bone volume necessary for osseous restoration or fixation, to facilitate this integration process.
Indication for Allografts
The structural features and multishaping possibilities make OCA suitable for the treatment of a wide spectrum of diseases, which can be grouped into two main paradigms ( Table 13.1 ). The first treatment paradigm includes complex reconstruction procedures to address such conditions as posttraumatic deformity, degenerative lesions associated with intra-articular fracture malunion, most commonly of the tibial plateau,40,41 and unicompartmental arthrosis or multifocal chondrosis, including patellofemoral degeneration.42–44 This group also includes massive type 3 or 4 OCD,9,10 osteonecrosis,45 as well as other diseases primarily affecting the subchondral bone. The second treatment paradigm addresses conditions primarily affecting articular cartilage. These include large chondral defects treated primarily with allografts or defects that have been previously treated by another cartilage repair technique such as microfracture, osteochondral autograft transfer, or autologous chondrocyte implantation that have failed or that have developed compromise of the subchondral bone.
Although the knee is the most common joint for osteochondral allografting, experience in other joints has been reported. Several case series have been reported in the ankle joint. Good results have been shown with the use of allografts in the treatment of large osteochondral lesions of the talus.46–50 Mixed results have been demonstrated for bipolar shell grafting for ankle osteoarthritis.51,52 Experience with allografts has also been described in the hip or in the shoulder, as treatment of femoral or humeral head osteonecrosis, or for osteochondral lesions associated with shoulder instability.53–55
As allografting procedure in the knee is used to treat a wide spectrum of diseases, the surgical technique is strictly related to the characteristics of the lesion and the surface to be grafted. Common to all the techniques is the use of a tourniquet and a leg positioner able to hold the knee in varying degrees of flexion (70 to 130 degrees). Before the surgical incision on the patient it is mandatory to inspect the graft, to verify its integrity and appropriate sizing. Generally a midline incision is performed, and the joint is entered medially or laterally depending on the lesion location. Retractors are positioned with care in protecting menisci, healthy cartilage, and cruciate ligaments. The lesion is then visualized, mapped, and treated with the most appropriate technique. Most femoral condyle lesions can be treated with plug or dowel grafts but occasionally a shell (posterior fem-oral condyle) or small fragment graft (tibial plateau or patella) is necessary.
Femoral Plug Grafts
The ideal lesion candidate for this treatment is a chondral or osteochondral defect in an easily accessible surface of the knee ( Fig. 13.1 ). Once plugs have been chosen as the ideal technique the lesion is mapped with multiple diameter-sizing dowels to plan the reconstruction. In case of wide lesion multiple plugs can be used to resurface the entire affected area, and in this case it is mandatory to proceed sequentially with the plugs in anteroposterior or posteroanterior direction. The position identified with the sizing dowel is fixed with a guide wire and the lesion is drilled with a reamer of the same diameter to 5 to 7 mm in depth to minimize the bone component of the graft. In selected cases of massive subchondral bone disruption the reaming depth can exceed 7 mm to position the plug onto a healthy bony tissue. After the guide wire removal, measurements are taken at the four poles of the reamed lesion. The plug is then harvested from the graft with a graft-harvesting reamer in the corresponding area of the lesion site to better match the condyle curvature. The depth measurements are transferred to the plug and the excess of bone is resected. After high-pressure lavage to remove marrow elements, the plug is positioned onto the recipient site and carefully tamped into place or compressed into the site with the help of passive joint range-of-motion forces. It is important to press-fit the graft with low-energy impacts to minimize chondrocyte injury.56,57 If necessary, fixation can be augmented with bioabsorbable screws or chondral darts. When additional plugs are required that are either juxtaposed or partially overlapped, care should be taken not to dislodge the first graft when reaming for the second. A standard closure concludes the procedure. Postoperatively, patients are maintained in a partial weight-bearing status for a period of 4 to 12 weeks and followed radiographically at regular intervals until radiographic evidence of graft incorporation.