1. Aetna considers allograft transplant of the knee (knee ligaments, osteochondral, and meniscus) medically necessary when selection criteria are met.

   Anterior Cruciate Ligament (ACL), Posterior Cruciate Ligament (PCL), Medial Collateral Ligament, (MCL), and Lateral Collateral Ligament (LCL):

   1. Members with ligament deficiency who are not candidates for autogenous transplantation (e.g., individuals whose autogenous tissues have been compromised by previous surgery, previous injury), or 
   2. Members with pathology such as chronic patellar tendonitis, and hamstring injury, or

   3. Members with any other contra-indications to using their own tissue such as collagen disease or generalized ligamentous laxity.

   Osteochondral:

   1. Avascular necrosis lesions of the femoral condyle; or
   2. Non-repairable stage 3 or 4 osteochondritis dissecans; or
   3. Otherwise healthy, active, non-elderly members who have either failed earlier arthroscopic procedures or are not candidates for such procedures because of the size, shape, or location of the lesion; or

   4. Treatment of an isolated, traumatic injury that is full-thickness depth (grade 4, down to and/or including the bone) lesion, preferably surrounded by normal, healthy (non-arthritic) cartilage.  The opposing articular surface should be generally free of disease or injury.

   Meniscus:

   1. Degenerative changes must be absent or minimal, and
   2. Knee must be stable (i.e., intact or reconstructed ACL), and
   3. Members under the age of 55 years, and 

   4. Pre-operative studies (MRI or previous arthroscopy) reveal absence or near-absence of the meniscus.

   Aetna considers allograft transplant of the knee experimental and investigational for all other indications because its effectiveness for indications other than the ones listed above has not been established.

2. Aetna considers osteochondral allograft of the talus experimental and investigational because there are unanswered questions regarding the clinical outcomes of this approach when compared with ankle arthrodesis, especially in terms of pain, disability, functionality and durability. 

   Aetna considers the use of vascularized bone graft for the treatment of avascular necrosis of the talus experimental and investigational because its effectiveness has not been established.

3. Aetna considers osteochondral allograft experimental and investigational for tarso-metatarsal arthrodesis, repairing chondral defects/lesions of the elbow, patella, patello-femoral ligament, and shoulder (e.g., Hill Sachs lesions) because its effectiveness has not been established.

4. Aetna considers the use of TruFit Plug (a synthetic resorbable biphasic implant) for osteochondral allografts of the knee experimental and investigational because its effectiveness has not been established.

5. Aetna considers the use of DeNovo NT tissue graft for repair of articular cartilage lesion experimental and investigational because its effectiveness has not been established.

Repair of knee ligaments refers to surgical treatment of acute injuries (ruptures), whereas primary reconstruction usually refers to surgical intervention of ligamentous laxity (chronic insufficiency) several months following an injury.  Revision reconstruction means corrective surgery when the original reconstruction has failed.  The bulk of the literature on ligamentous reconstruction of the knee deals with the primary reconstruction of the anterior cruciate ligament (ACL).  Generally, there are 3 reconstructive methods for managing ACL insufficiency: (i) intra-articular replacements, (ii) extra-articular procedures, and (iii) combined procedures.  The first method is intended to replace the ACL, whereas the second method is intended to tighten the medial or lateral secondary restraints, or both in the third method.  The sources for intra-articular replacements are quadriceps tendon, patellar tendon, hamstring tendons, and iliotibial band or tract.  In particular, the bone-patellar tendon-bone autograft (the central one-third of the patellar tendon and its bony attachments to the patella and tibial tubercle) is the most common operation currently performed for reconstructing the ACL through arthroscopy.

Allograft, also known as allogeneic graft or homograft, is a graft between individuals of the same species, but of dissimilar genotype.  For tendon allografts, cadaver donors are usually used.  The donor tissues most commonly used are the patellar and Achilles tendons.  An allograft may be preserved by freeze-drying or deep-freezing and can be sterilized either by sterile procurement with careful donor screening or by secondary sterilization with gaseous ethylene oxide or gamma irradiation.  It is believed that freeze-drying or deep-freezing renders connective tissue allografts less immunogenic by killing the cells and denaturing surface histocompatibility antigens.  However, while some investigators have claimed that freeze-drying of the allograft does not significantly change the mechanical properties of the grafts compared with deep-freezing; others have reported frequent late failures of freeze-dried allograft tissues.  Fideler and co-workers (1994) concluded that a dose of 30,000 or 40,000 gray (3 or 4 megarad) of gamma radiation is necessary for the inactivation of the DNA of the human immunodeficiency virus in frozen bone-patellar ligament-bone allograft harvested from donors infected with the virus.

Tendon allograft has been used for the repair/reconstruction of the ACL in patients following major knee injury.  The advantages of using these allografts are a more abundant supply of tissue for multiple ligament and revision surgery, a shorter operative time, faster rehabilitation, avoidance of morbidity associated with autograft harvesting, as well as a lower incidence of stiff knee.  On the other hand, the disadvantages in employing allografts are a potentially increased failure rate, a risk of hepatitis or AIDS infection, as well as stimulation of an immune response.

Studies have shown high failure rates with use of allograft for ACL reconstruction (Gorschewsky et al, 2005; Pritchard et al, 1995; Roberts et al, 1991).  Prodromos et al (2007) performed a meta-analysis of autograft and allograft stability data.  Normal stability for all autografts was 72 % versus 59 % for all allografts (p < 0.01).  Abnormal stability was 5 % for all autografts versus 14 % for all allografts (p < 0.01).  Bone-patellar-tendon-bone (BPTB) autograft normal stability was 66 % versus 57 % for BPTB allografts (p < 0.01).  Abnormal BPTB autograft stability was 6 % versus 16 % for BPTB allograft.  Hamstring autograft normal or abnormal stability rates were 77 % and 4 % and were compared to soft tissue allografts as a group which were 64 % and 12 % (p < 0.01).  The investigators reported that allografts had significantly lower normal stability rates than autografts.  The investigators found that allograft abnormal stability rate, which usually represents graft failure, was nearly 3 times higher than that of autografts.  The investigators concluded that autografts are the graft of choice for routine ACL reconstruction with allografts better reserved for multiple ligament-injured knees where extra tissue may be required.

A meta-analysis of patellar autograft versus allograft for ACL reconstruction found better outcomes with autograft (Krych et al, 2008).  The investigators noted, however, that when irradiated and chemically processed allografts are excluded, the outcomes of autograft and allograft are more similar, but without the irradiation or chemical processing of allografts, there is an increased risk of transmission of infection.

A guidelines panel from the Italian National Guidelines System (Romanini et al, 2010) conducted a critical review of the literature of grafts for arthroscopic ACL reconstruction, and found that "[a]utograft shows moderate superiority compared with allograft" and that "[a]vailable evidence allows recommendation of use of autograft over allograft in arthroscopic ACL reconstruction."  The guidelines panel also found that, for autograft, patellar tendon has better performance than hamstring.  The guidelines panel also concluded that "[i]t is also appropriate to consider allograft and artificial ligaments only in very selected cases, discouraging widespread use, given the potential risks and paucity of well-performed, well-designed clinical studies."

Reinhard et al (2010) conducted a systematic review of the evidence for graft selection in ACL reconstruction.  The investigators found limited high-quality evidence comparing autograft to allograft.  Most case series include a smaller number of young patients (i.e., less than 30 years of age) and there have been early reports of unacceptably high failure rates in young patients.  The authors stated that procurement, storage, sterilization, and processing of allografts vary widely within the industry.  The investigators noted that the sterilization process may affect the mechanical characteristics of allografts, and that this process is necessary to decrease viral disease transmission and bacterial infection rate, but it may also adversely affect the quality of the tissue.  The review stated that several techniques have been used for this purpose.  The review found that, although ethylene oxide sterilization does not alter directly the mechanical properties of the graft, it has been shown to cause clinical failure because of persistent synovitis, and therefore is less favorable.  Another sterilization technique involves applying irradiation.  The authors stated that high-dose irradiation (3 Mrad or more) is unacceptable as it severely affects mechanical properties of the tissue.  The authors stated that lower doses of irradiation (2 to 2.5 Mrad) has also been shown in several studies to cause unacceptable inferior clinical outcomes and high failure rates..

Other more recent studies have found lower failure rates with patellar tendon autograft than allograft and/or hamstring autograft (Barrett et al, 2011; Barrett et al, 2010; Mehta et al, 2010).

Dopirak and colleagues (2008) noted that there has been substantial progress in the understanding of the medial patello-femoral ligament during the past 10 years.  This structure is the primary static soft-tissue restraint to lateral patellar displacement.  Substantial alteration of normal patellar tracking occurs after sectioning of the ligament.  Clinical studies have demonstrated the medial patello-femoral ligament is disrupted during acute patellar dislocation.  Recently, several medial patello-femoral ligament-based procedures have been developed for the treatment of patellar instability with good early results.  However, the authors stated that further studies are needed to define the exact role of these procedures in the treatment of patello-femoral instability.

Oro et al (2011) compared operating room time and costs associated with ACL reconstruction with either bone-patellar tendon-bone (BPTB) autograft or BPTB allograft.  The total mean cost per case was 25 % higher in the allograft group compared with the autograft group.  The mean operating room time was only 12 mins greater in autograft cases.  Other studies have found significantly higher costs with use of allograft than autograft in ACL reconstruction, with little differences in operating room costs (Cooper and Kaeding, 2010; Naqda et al, 2010).

There is inadequate evidence that the use of tendon allograft is equally effective as autograft in the primary reconstruction of ACL.  In addition, due to the risk of disease transmission, it should not be used for primary, isolated ACL reconstruction.  Tendon allograft for reconstruction of the ACL should only be employed when an adequate autologous graft is not available for (i) revision surgery (in knees in which a primary reconstruction of the ligament had failed and in which an autograft had already been used) or for (ii) primary reconstruction surgery for combined ligament injuries (ACL and either the posterior cruciate ligament, or medial collateral ligament) when an adequate autologous graft is not available.

There are relatively few studies comparing allograft to autograft in posterior cruciate ligament (PCL) reconstruction.  In an evidence review of outcomes of posterior collateral ligament treatment, Hammoud et al (2010) cited evidence of good results with Achilles allograft and hamstring autograft for posterior cruciate ligament reconstruction.  Hermans et al published a 6- to 12-year follow-up (mean 9.1 years) study of single bundle PCL reconstruction.  Twenty-two patients (88 % follow-up) with isolated PCL injuries underwent reconstruction using patellar tendon autograft (n = 9), 4-strand hamstring tendon autograft (n = 7), 2-strand hamstring tendon autograft plus Achilles tendon allograft (n = 8), or Achilles tendon allograft alone (n = 1).  The authors reported that there were no differences between grafts used in mean Lysholm score, Tegner score, or International Knee Documentation Committee (IKDC) rating between the patellar tendon and hamstring tendon reconstructions. 

Williams and Gamradt (2008) noted that the creation of cartilage repair tissue relies on the implantation or neosynthesis of cartilage matrix elements.  One cartilage repair strategy involves the implantation of bioabsorbable matrices that immediately fill a chondral or osteochondral defect.  Such matrices support the local migration of chondrogenic or osteogenic cells that ultimately synthesize new ground substance.  One such matrix scaffold, TruFit Plug, a synthetic resorbable biphasic implant, is a promising device for the treatment of osteochondral voids.  The implant is intended to serve as a scaffold for native marrow elements and matrix ingrowth in chondral defect repair.  The device is a resorbable tissue regeneration scaffold made predominantly from polylactide-coglycolide copolymer, calcium sulfate, and polyglycolide.  It is approved in Europe for the treatment of acute focal articular cartilage or osteochondral defects but is approved by the U.S. Food and Drug Administration only for backfill of osteochondral autograft sites.  Pre-clinical studies demonstrated restoration of hyaline-like cartilage in a goat model with subchondral bony incorporation at 12 months.  Early clinical results of patients enrolled in the Hospital for Special Surgery Cartilage Registry have been favorable, with a good safety profile.

Carmont et al (2009) stated that TruFit plugs are synthetic polymer scaffolds that are inserted into an articular surface to provide a stable scaffold to encourage the regeneration of a full thickness of articular cartilage to repair chondral defects.  These researchers reported promising early results for the repair of small articular cartilage defects within the knee.  Others have reported "failures" in which patients have complained of persistent symptoms and joint effusion at 6 months after plug insertion and arthroplasty has been undertaken.  These investigators reported a case of delayed incorporation of an articular cartilage defect of the lateral femoral condyle treated with 3 TruFit plugs.  The patient eventually reported symptom alleviation and resumption of functional activity after 24 months of continued rehabilitation.  The authors recommended that patients with continued symptoms persevere with rehabilitation and allow the regenerating articular cartilage time to mature fully before considering undertaking irreversible arthroplasty procedures.

The clinical value of TruFit Plug for osteochondral allografts of the knee has not been established.

Severe post-traumatic ankle arthritis poses a reconstructive challenge in the young and active patient.  Bipolar fresh osteochondral allograft (BFOA) may represent an intriguing alternative to arthrodesis and prosthetic replacement.  Giannini et al (2010) described a lateral trans-malleolar technique for BFOA, and evaluated the results in a case series.  A total of 32 patients, mean age of 36.8 +/- 8.4 years, affected by ankle arthritis underwent BFOA with a mean follow-up of 31.2 months.  The graft was prepared by specifically designed jigs, including the talus and the tibia with the medial malleolus.  The host surfaces were prepared by the same jigs through a lateral approach.  The graft was placed and fixed with twist-off screws.  Patients were evaluated clinically and radiographically at 2, 4, and 6 months after operation, and at a minimum 24 months follow-up.  A biopsy of the grafted areas was obtained from 7 patients at 1-year follow-up for histological as well as immunohistochemical examination.  Pre-operative AOFAS score was 33.1 +/- 10.9 and post-operatively 69.5 +/- 19.4 (p < 0.0005).  Six failures occurred.  Cartilage harvests showed hyaline-like histology with a normal collagen component but low proteoglycan presence and a disorganized structure.  Samples were positive for MMP-1, MMP-13 and Capsase-3.  The authors concluded that the use of BFOA represents an intriguing alternative to arthrodesis or arthroplasty; precise allograft sizing, stable fitting and fixation and delayed weight-bearing were key factors for a successful outcome.  They stated that further research regarding the immunological behavior of transplanted cartilage is needed.

Injury of articular cartilage due to trauma or pathological conditions is a major cause of disability worldwide.  There is extensive ongoing reseach focusing on strategies to repair and replace knee joint cartilage.  DeNovo NT Graft has been used to treat focal articular defects in a wide range of anatomical applications (e.g., ankle, elbow, great toe, hip, knee, and shoulder). DeNovo NT Natural Tissue Graft, a human tissue allograft, is an available cartilage repair treatment in the United States.  DeNovo ET Engineered Tissue Graft is undergoing a clinical study as an investigational biological product currently underoing clinical tials.  Moreover, there is a lack of evidence regarding the clinical value of DeNovo tissue graft.

Ahmed and Hincke (2010) discussed strategies to repair and replace knee joint cartilage.  Because of inadequacies associated with widely used approaches, the orthopedic community has an increasing tendency to develop biological strategies, which include transplantation of autologous (i.e., mosaicplasty) or allogeneic osteochondral grafts, autologous chondrocytes (autologous chondrocyte transplantation), or tissue-engineered cartilage substitutes.  Tissue-engineered cartilage constructs represent a highly promising treatment option for knee injury as they mimic the biomechanical environment of the native cartilage and have superior integration capabilities.  Currently, a wide range of tissue-engineering-based strategies are established and investigated clinically as an alternative to the routinely used techniques (i.e., knee replacement and autologous chondrocyte transplantation).  Tissue-engineering-based strategies include implantation of autologous chondrocytes in combination with collagen I, collagen I/III (matrix-induced autologous chondrocyte implantation), HYAFF 11 (Hyalograft C), and fibrin glue (Tissucol) or implantation of minced cartilage in combination with copolymers of polyglycolic acid along with polycaprolactone (cartilage autograft implantation system), and fibrin glue (DeNovo NT natural tissue graft).  Tissue-engineered cartilage replacements show better clinical outcomes in the short-term, and with advances that have been made in orthopedics they can be introduced arthroscopically in a minimally invasive fashion.  Thus, the future is bright for this innovative approach to restore function.

Kruse et al (2012) presented the findings of a new technique using DeNovo NT juvenile allograft cartilage implantation introduced into a talar lesion arthroscopically in a single procedure to repair a posterio-medial talar osteochondral defects in a healthy, active 30-year old female.  The patient tolerated the procedure well.  At the 6-month follow-up visit, the patient had returned to full activity, and at 24 months, she remained completely pain-free.  The findings of this case study need to be validated by well-designed studies.