Osteochondral Autografts (Mosaicplasty, OATS)

Number: 0637

Policy

1. Aetna considers osteochondral autografts (OATS or mosaicplasty) medically necessary for symptomatic focal full-thickness articular cartilage defects of the knee when all of the following criteria are met:

   1. The member is skeletally mature with documented closure of growth plates (e.g., 15 years or older); and
   2. The member is not considered a candidate for total knee replacement (i.e., member is under 55 years of age); and
   3. The member has disabling symptoms limiting ambulation that have not been relieved by appropriate non-surgical therapies (e.g., medication, physical therapy); and
   4. The member has focal, full thickness (grade III or IV) unipolar lesions on the weight bearing surface of the femoral condyles or trochlea; and
   5. The member has minimal to absent degenerative changes in the surrounding articular cartilage (Outerbridge grade II or less) and normal appearing hyaline cartilage surrounding the border of the defect; and
   6. Stable and aligned knee with intact meniscus and normal joint space on X-ray (a corrective procedure in combination with, or prior to, chondrocyte implantation may be necessary to ensure stability, alignment and normal weight distribution within the joint); and
   7. The opposing articular surface should be generally free of disease or injury.

2. Aetna considers all of the following procedures experimental and investigational because their effectiveness has not been established:

   1. Autologous cartilage chip transplantation for osteochondral repair
   2. Hybrid autologous chondrocyte implantation performed with osteochondral autograft transfer system (Hybrid ACI/OATS) technique for the treatment of osteochondral defects;
   3. Osteochondral autografts (OATS, mosaicplasty) of other joints (ankle, elbow, hip, patella, shoulder);
   4. Osteochondral autograft transplantation for the treatment of Freiberg disease or repair chondral defects of the elbow, patella, shoulder, or joints other than the knee.

3. Aetna considers non-autologous mosaicplasty using resorbable synthetic bone filler materials (including but not limited to plugs and granules) to repair osteochondral defects of the ankle or knee experimental and investigational because their effectiveness has not been established.

4. Aetna considers the use of minced articular cartilage (whether synthetic, allograft or autograft) to repair osteochondral defects of the ankle or knee experimental and investigational because its effectiveness has not been established.

5. Aetna considers the use of synthetic resorbable polymers (e.g., PolyGraft BGS, TruFit [cylindrical plug], TruGraft [granules]) to repair osteochondral articular cartilage defects experimental and investigational because their effectiveness has not been established.

6. Aetna consdiers combination of adipose-derived stem cells and mosaicplasty for repair of osteochondral defects experimental and investigational because the effectiveness of this approach has not been established.

7. Aetna considers combination of autologous chondrocyte implantation and osteochondral autograft transfer for repair of knee osteochondral lesion experimental and investigational because the effectiveness of this approach has not been established.

Background

Articular cartilage damaged through acute or chronic trauma or osteochondritis dissecans has limited ability to regenerate, resulting in persistent joint line pain, recurrent synovitis and altered joint mechanics most commonly in weight-bearing joints. Loose bodies may develop, which may then cause joint destruction, restricted mobility and/or locking. Long standing severe damage to the articular cartilage can lead to debilitating osteoarthritis, which ultimately may require a total knee arthroplasty. Current therapeutic options include lavage and debridement, which may offer pain relief for up to several years, but offer no prospect of long-term cure. Similarly, marrow-stimulation techniques such as drilling or microfracture of the subchondral bone of cartilage lesions and abrasion arthroplasty may fail to provide long-term solutions because these procedures usually promote the development of fibrocartilage, which may be less durable than the hyaline cartilage that normally covers articular surfaces.

Osteochondral autografts have been examined as an alternative to allografts for the treatment of osteochondral defects. An osteochondral defect is any type of damage to articular cartilage and underlying (subchondral) bone. Osteochondral autograft transplant (OAT) involves the transplantation of small plugs of healthy bone and hyaline cartilage from joint areas with less weight bearing. The most common donor sites are the areas of the knee or ankle (on the same side). Small holes are drilled through the lesion and the newly harvested plugs are inserted into the holes. Two related procedures have been investigated:

1. mosaicplasty, and
2. the osteochondral autograft transfer system (OATS).

Mosaicplasty is a reconstructive bone grafting procedure for the treatment of articular defects of the knee. Mosaicplasty consists of removing small osteochondral cylinders from low weight bearing surfaces of the affected joint or another joint in the same individual and transplanting them in a mosaic-like formation into focal chondral or osteochondral defects in the knee. It is usually utilized to treat larger defects. In general, treatment of articular defect of the knee by mosaicplasty entails transplantation of small cylindrical osteochondral grafts (4 to 10 mm in diameter, 15 to 20 mm deep) from the less weight-bearing periphery of the femoral condyles at the level of the patello-femoral joint, and transplanting them in a mosaic-like fashion into a prepared defect site on the weight-bearing surfaces of the same knee. Its goal is to produce a smooth gliding articular surface of hyaline or hyaline-like cartilage in weight-bearing surfaces of the knee. Mosaicplasty is carried out either by an open approach or arthroscopically if the defect/lesion is small and not more than 4 to 6 grafts are needed. Both open and arthroscopic mosaicplasty require a relatively short rehabilitation period – normal daily activity can be allowed after 5 to 8 weeks.

Animal studies and subsequent clinical trials have demonstrated the survival of transplanted hyaline cartilage. In addition, there are limited studies comparing the results of mosaicplasty with other established procedures. However, long-term data are limited and it is unclear whether mosaicplasty can prevent further deterioration in the affected articular cartilage.

In a review on treatment osteochondral injuries of the knee, Cain and Clancy (2001) stated that the treatment of osteochondral fractures and osteochondral lesions in the knee is controversial. Although the results of many reconstructive procedures (e.g., autologous osteochondral mosaicplasty and osteochondral allograft transplantation) are quite encouraging with early follow-up, the ultimate goal is to prevent long-term degenerative arthritis. Only well-designed prospective studies with long-term follow-up will determine the effectiveness of these procedures in reaching the ultimate goal.

In a review on management of osteochondral injuries of the knee, Alleyne and Galloway (2001) stated that the management of articular cartilage lesions has yet to reveal a "right answer", and that long-term follow-up studies of all of the techniques reviewed are needed to give definitive answers about the durability of the repaired and transplanted tissues.

In a review on mosaicplasty for the treatment of osteochondral defects of the ankle joint, Mendicino and associates (2001) stated that this procedure shows excellent promise for use in the ankle and warrants larger investigational studies to assess outcomes. In a randomized, clinical trial (n = 100),

Guidelines from the American College of Rheumatology on management of osteoarthritis (OA) of the hip and knee state that autologous osteochondral plugs (mosaicplasty) is being investigated for repair of focal chondral defects, but that this procedure is "not currently indicated in the treatment of patients with OA" (Altman et al, 2000).

An assessment of mosaicplasty for knee cartilage defects from the National Institute for Health and Clinical Excellence (NICE, 2006) concluded: "Current evidence suggests that there are no major safety concerns associated with mosaicplasty for knee cartilage defects. There is some evidence of short-term efficacy, but data on long-term efficacy are inadequate. In view of the uncertainties about the efficacy of the procedure, it should not be used without special arrangements for consent and audit or research."

More recently, an assessment of mosaicplasty for knee cartilage defects by the Institute for Clinical Effectiveness and Health Policy (Pichon-Riviere, et al., 2009) concluded: "At present, there is not good quality evidence that would allow the assessment of mosaicplasty versus other techniques. There are few clinical trials, with different surgical techniques; different rehabilitation protocols and outcomes evaluated using different scales. Additionally, these studies presented different follow-up periods which does not allow result comparison with others where surgical follow-up was not performed; it does not it allow long-term morbidity assessment of the graft donation site either. Because of the poor methodological quality of the studies, it is not possible to make specific recommendations on its use, considering it as experimental."

The osteochondral autograft transfer system (OATS) is a procedure employed for medium sized areas of discrete damage (mosaicplasty is employed for even larger but discrete areas of damage). This procedure is similar to mosaicplasty; however, it involves the use of a larger, single plug that usually fills an entire defect (eg, those associated with anterior cruciate ligament [ACL] tears).

The OATS procedure focuses on chondral defects that are associated with chronic tears of the anterior cruciate ligament (ACL), using an arthroscopic approach that can provide access to both the ACL for reconstruction and performance of the autograft. The orthopedic surgeon uses an apple-corer like instrument to core out a circle of damaged cartilage and replaces it with a piece of normal cartilage from a less important part of the same knee. The underlying principal is that the transferred cartilage will grow to cover the edges of the core with proper cartilage cells and not the weaker fibrocartilage cells.

Bobic (1996) reported the results of a case-series study (n = 12) regarding the use of OATS in patients with ACL-deficient knees. The series examined arthroscopic osteochondral autograft transplantation in conjunction with ACL reconstruction using bone-patellar tendon-bone autograft. Eight procedures were primary, and 4 were revisions of failed synthetic grafts. Chondral lesions in this series ranged from 10 to 22 mm in diameter. Donor site was selected prior to notchplasty, and 3 to 5 osteochondral cylinders, 5 to10 mm in diameter, 10 to15 mm long, were harvested. The author stated that improved surgical technique, tubular cutting instruments enabling minimal damage to harvested articular cartilage, and press-fit insertion yielded promising uniform results in 10 of 12 cases with 2 years' follow-up.

Wang (2002) reported a retrospective study of 15 patients with 16 knees who underwent osteochondral autografts for focal full thickness articular cartilage defects of the knee. Two to 4 years follow-up of these patients showed 80 % good or excellent clinical results. There was no correlation of the clinical results with the underlying diagnoses, including osteonecrosis, osteochondritis dissecans and traumatic cartilage defect, or a size of the lesion smaller than 600 mm2. However, cartilage lesions larger than 600 mm2 were associated with increasing fibrous tissue formation and fissuring between the grafts and the host tissues and poor results. The improvement in symptoms appeared time-dependent, ranging from 6 to 16 weeks, suggesting that post-operative protection of the graft is warranted. There was no radiographical progression of degenerative changes of the knee on the medium-term follow-up.

The BlueCross BlueShield Association Technology Evaluation Center (2003) stated that autogenous osteochondral transplantation (OATS or mosaicplasty) are not established treatments for chondral defects. "Although preliminary reports" of autogenous osteochondral transplantation (OATS or mosaicplasty) "appear favorable, only limited outcome data are available on this technology."

Sharpe et al (2005) reported their 3-year post-operative findings on the use of a combination of autologous chondrocyte implantation (ACI) and the OATS procedure as a treatment option for the repair of large areas of degenerative articular cartilage. Osteochondral cores were used to restore the contour of articular cartilage in 13 patients with large lesions of the lateral femoral condyle (n = 5), medial femoral condyle (n = 7) and patella (n = 1). Autologous cultured chondrocytes were injected underneath a periosteal patch covering the cores. After 1 year, patients had a significant improvement in their symptoms and after 3 years this level of improvement was maintained in 10 of the 13 patients. Arthroscopic examination revealed that the osteochondral cores became well integrated with the surrounding cartilage. These investigators concluded that the hybrid ACI/OATS technique provides a promising surgical approach for the treatment of patients with large degenerative osteochondral defects.

Scheibel and colleagues (2004) performed 8 osteochondral autologous transplantations from the knee joint to the shoulder. All patients (2 women and 6 men; mean age of 43.1 years) were documented prospectively. In each patient the stage of the osteochondral lesion was Outerbridge grade IV with a mean size of the affected area of 150 mm2. All patients were assessed by using the Constant score for the shoulder and the Lysholm score for the knee. Standard radiographs, magnetic resonance imaging and second-look arthroscopy were used to evaluate the presence of glenohumeral osteoarthritis and the integrity of the grafts. After a mean of 32.6 months (8 to 47), the mean Constant score increased significantly. Magnetic resonance imaging revealed good osseo-integration of the osteochondral plugs and congruent articular cartilage at the transplantation site in all but 1 patient. Second-look arthroscopy performed in 2 cases revealed a macroscopically good integration of the autograft with an intact articular surface. The authors noted that osteochondral autologous transplantation in the shoulder appears to offer good clinical results for treating full-thickness osteochondral lesions of the glenohumeral joint. However, they also noted that the findings of their study suggest that the development of osteoarthritis and the progression of pre-existing osteoarthritic changes cannot be altered by this technique.

The Institute for Clinical Effectiveness and Health Policy (Pichon-Riviere et al, 2006) evaluated the literature on the effectiveness of OATS and mosaicplasty on ankle bone cartilage lesions. The assessment concluded: "There is still not enough evidence available on the efficacy of mosaicplasty or the OATS procedure for the treatment of talus cartilage joint lesions. There is very little published about the assessment of the osteochondral grafting viability. There is not enough evidence determining whether the tissues coming from places that do not carry weight could absorb the stress of weight bearing areas, neither the degree of donor site morbidity. Patient inclusion criteria are not well settled in the literature, and there is no uniform consensus on the procedure's indication. ...Only well designed prospective clinical trials with long follow-ups could determine the efficacy of these procedures to relieve the symptoms caused by osteochondral lesions, improve joint function and achieve the final objective, which is the prevention of secondary arthrosis."

Zengerink and colleagues (2010) compared the effectiveness of treatment strategies for osteochondral defects (OCD) of the talus. Electronic databases from January 1966 to December 2006 were systematically screened. The proportion of the patient population treated successfully was noted, and percentages were calculated. For each treatment strategy, study size weighted success rates were calculated. A total of 52 studies described the results of 65 treatment groups of treatment strategies for OCD of the talus: 1 randomized clinical trial was identified; 7 studies described the results of non-operative treatment, 4 of excision, 13 of excision and curettage, 18 of excision, curettage and bone marrow stimulation (BMS), 4 of an autogenous bone graft, 2 of trans-malleolar drilling (TMD), 9 of OATS, 4 of ACI, 3 of retrograde drilling, and 1 of fixation. OATS, BMS and ACI scored success rates of 87 %, 85 %, and 76 %, respectively. Retrograde drilling and fixation scored 88 % and 89 %, respectively. Together with the newer techniques OATS and ACI, BMS was identified as an effective treatment strategy for OCD of the talus. Because of the relatively high cost of ACI and the knee morbidity seen in OATS, the authors concluded that BMS is the treatment of choice for primary osteochondral talar lesions. However, due to great diversity in the articles and variability in treatment results, no definitive conclusions can be drawn. They stated that further sufficiently powered, randomized clinical trials with uniform methodology and validated outcome measures should be initiated to compare the outcome of surgical strategies for OCD of the talus.

Lu and Hame (2005) noted that treatment options for chondral and osteochondral defects of the patella have been few and results have been inconsistent at best. Autologous osteochondral transplantation presents a new way to revisit these patellar defects. These researchers reported the case of a young female softball player with a simple cyst in the patella and an osteochondral defect that serves as the indication for autograft osteochondral transplantation.

Nho et al (2008) stated that autologous osteochondral transplantation (AOT) has been successfully used in the femoral condyle and trochlea and is an attractive treatment option for full-thickness patellar cartilage lesions. These investigators hypothesized that patients treated with AOT for the repair of symptomatic, isolated patellar cartilage lesions will demonstrate improvement in functional outcomes and post-operative MRI appearance. In a case-series study, patients with focal patellar cartilage lesions treated with AOT were prospectively followed. The mean age at the time of surgery was 30 years. Clinical assessment was performed with the International Knee Documentation Committee (IKDC), activities of daily living of the Knee Outcome Survey (ADL), and Short Form-36 (SF-36) at baseline and most recent follow-up. Magnetic resonance imaging was used to evaluate the cartilage repair morphologic characteristics in 14 cases. Twenty-two patients met the study criteria with a mean follow-up of 28.7 months (range of 17.7 to 57.8 months). The mean patellar lesion size was 165.6 +/- 127.8 mm(2), and the mean size of the donor plug was 9.7 +/- 1.1 mm in diameter with 1.8 +/- 1.4 plugs/defect. The mean pre-operative IKDC score was 47.2 +/- 14.0 and improved to 74.4 +/- 12.3 (p = 0.028). The mean pre-operative ADL score was 60.1 +/- 16.9 and increased to 84.7 +/- 8.3 (p = 0.022). The mean SF-36 also demonstrated an improvement, from 64.0 +/- 14.8 at baseline to 79.4 +/- 15.4 (p = 0.059). Nine patients underwent concomitant distal re-alignment and demonstrated improvement between pre-operative and post-operative outcomes scores, but these differences were not statistically significant. Magnetic resonance imaging appearance demonstrated that all plugs demonstrated good (67 % to 100 %) cartilage fill, 64 % with fissures greater than 2 mm at the articular cartilage interface, 71 % with complete trabecular incorporation, and 71 % with flush plug appearance. The authors concluded that patellar AOT is an effective treatment for focal patellar chondral lesions, with significant improvement in clinical follow-up. This study suggested that patients with patellar mal-alignment may represent a subset of patients who have a poor prognostic outlook compared with patients with normal alignment. This was a small case-series study; its findings need to be validated by well-designed studies.

Colvin and West (2008) stated that recurrent patellar instability can result from osseous abnormalities, such as patella alta, a distance of greater than 20 mm between the tibial tubercle and the trochlear groove, and trochlear dysplasia, or it can result from soft-tissue abnormalities, such as a torn medial patellofemoral ligament or a weakened vastus medialis obliquus. Non-operative treatment includes physical therapy, focusing on strengthening of the gluteal muscles and the vastus medialis obliquus, and patellar taping or bracing. Acute medial-sided repair may be indicated when there is an osteochondral fracture fragment or a retinacular injury. The recent literature does not support the use of an isolated lateral release for the treatment of patellar instability. A patient with recurrent instability, with or without trochlear dysplasia, who has a normal tibial tubercle-trochlear groove distance and a normal patellar height may be a candidate for a reconstruction of the medial patello-femoral ligament with autograft or allograft. Distal re-alignment procedures are used in patients who have an increased tibial tubercle-trochlear groove distance or patella alta. The degree of anteriorization, distalization, and/or medialization depends on associated arthrosis of the lateral patellar facet and the presence of patella alta. Associated medial or proximal patellar chondrosis is a contraindication to distal realignment because of the potential to overload tissues that have already undergone degeneration.

Matricali et al (2010) stated that in order to perform an osteochondral autologous transplantation (OAT) or an autologous chondrocyte implantation (ACI), the integrity of healthy intact articular cartilage at a second location needs to be violated. This creates the possibility for donor site morbidity. Only recently have any publications addressed this issue. These researchers reviewed the current knowledge on donor site morbidity after an OAT or an ACI. Reports were identified by searching Medline and PubMed up to March 2010. Donor site morbidity was described mostly considering a clinical outcome, both in a qualitative (parameters in history or physical examination) and/or quantitative way (knee status reported by means of a numerical score). An increasing rate of problems is noted when using quantitative instead of qualitative parameters, and when donor site morbidity is the focus of attention, affecting up to more than 50 % of the patients, especially for an OAT procedure. The decision to harvest an osteochondral or cartilage biopsy to perform a repair procedure should therefore be taken with caution. This also underscores the need for further research to identify safe donor sites or to develop techniques that eliminate the need for a formal biopsy completely.

The Washington State Health Care Authority Technology Assessment Program (2011) commissioned a technology assessment of Osteochondral Allograft Transplantation and Autograft Transfer System (OATS/mosaicplasty). In commissioning the assessment, the Program stated: "Significant questions remain about the safety, efficacy and effectiveness, and cost effectiveness of OATS/mosaicplasty cartilage surgery. The  choice of suitable patients for OATS/mosaicplasty surgery is controversial because the size and number of damage sites for which it is functional are not well defined, because the harvesting of cartilage from another site or cadaver tissue adds risk and healing issues, and because other, less invasive procedures may be equally effective in the short term (autologous chondrocyte injection). Effectiveness questions particularly center on whether the potential beneficial outcomes of long term pain and functional improvement, prevention of osteoarthritis or further joint deterioration occur with this surgical intervention."

The systematic evidence review prepared for the Washington State Health Care Authority (Skelly et al, 2011) reported that two small randomized controlled trials (RCTs) (level of evidence IIb) in younger populations compared OAT with microfracture and three RCTs (or quasi RCTs, level of evidence IIb) compared OAT/mosaicplasty with ACI in general (older)populations. The review found substantial differences in patient populations, lesion sizes, comparators and outcomes measures used across studies, making it difficult to draw overall conclusions. Compared with microfracture (MF), OAT was associated with better patient-reported (based on International Cartilage Repair Society (ICRS) cartilage repair assessment), and clinician-reported (based on the Hospital for Special Surgery (HSS) Score) functional outcomes in young athletes and children based on two small RCTs (total n = 104) (citing Gudas, et al., 2005; Gudas, et al., 2009). For comparisons with ACI, three poor quality RCTs in general (older) populations reported functional outcomes. Two small, poor quality RCTs suggest that function based on patient-reported outcomes (Lysholm Knee Scoring Scale and a modification of it) was better for OAT compared with ACI; however statistical significance was reached in only one of the RCTs (n = 40) (citing Horas, et al., 2003) and in the other RCT (citing Dozin, et al., 2005), conclusions are difficult given the significant loss to follow-up (50%). The largest RCT (n = 100) (citing Bentley, et al., 2003) reported that a significantly smaller proportion of participants receiving mosaicplasty had excellent or good results based on the author’s modification of the Cincinnati Rating Scale. One of the smaller RCTs reported no significant differences in the Meyer score. Both these studies included substantial proportions of participants who had prior surgeries (94% and 45% respectively).

The assessment (2011) found that there were substantial differences across studies with respect to populations, lesion sizes, comparators and outcomes measures making it difficult to draw overall conclusions. The indications for OAT versus mosaicplasty, autograft versus allograft appear to be based on case series primarily. The majority of studies are in populations less than 50 years of age. The overall quality of the literature is poor, particularly with respect to evaluation of autograft.

The Washington State Health Care Authority Agency Medical Directors (2011) concluded that there is some evidence of benefit of osteochondral transplantation procedures in cases failing conservative management. The agency noted that the evidence of effectiveness and efficacy of osteochondral transplantation procedures is of low quality and shows variable outcomes. The agency found that the case selection criteria for osteochondral transplantation procedures is uncertain and that there are no long-term outcomes data. They stated that osteochondral transplantation is an evolving technology with a weak evidence base, and that the long-term safety and effectiveness are uncertain. They noted the potential for overuse and misuse given the lack of patient and technique selection criteria. The agency recommended coverage of osteochondral transplantation procedures only for the knee (and possibly talus) in person less than 50 years of age who have failed conservative management and who do not have arthritis. 

The Washington State Health Care Authority Health Technology Clinical Committee (2012) has concluded that osteochondral allograft/autograft transplantation for the knee is a covered benefit when the following conditions are met:

1. age less than 50 years, older at the discretion of the agency;
2. excluding malignancy, degenerative and inflammatory arthritis in the joint; and
3. single focal full-thickness articular cartilage defect.

The Committee stated that osteochondral allograft/autograft transplantation is not covered for joints other than the knee.

Non-autologous mosaicplasty has been proposed as an alternative to conventional mosaicplasty.  Non-autologous mosaicplasty entails a series of small holes drilled into the area of the osteochondral defect.   The holes are then packed with a synthetic polymer (as a bone void filler); providing a scaffold for the growth of new bone.   The synthetic graft is gradually resorbed by the body and replaced with bone.   The proposed advantage of this procedure over conventional osteochondral autograft transplantation is the elimination of the need for harvesting bone and cartilage from a donor graft site.  However, there is currently insufficient evidence to support the use of non-autologous mosaicplasty for repair of osteochondral defects.

Lu and colleagues (2006) stated that traumatic articular cartilage injuries heal poorly and may predispose patients to the early onset of osteoarthritis.  One current treatment relies on surgical delivery of autologous chondrocytes that are prepared, prior to implantation, through ex-vivo cell expansion of cartilage biopsy cells.  The requirement for cell expansion, however, is both complex and expensive and has proven to be a major hurdle in achieving a widespread adoption of the treatment.  These researchers presented evidence that autologous chondrocyte implantation can be delivered without requiring ex-vivo cell expansion.  The proposed improvement relies on mechanical fragmentation of cartilage tissue sufficient to mobilize embedded chondrocytes via increased tissue surface area.  The authors’ outgrowth study, which was used to demonstrate chondrocyte migration and growth, indicated that fragmented cartilage tissue is a rich source for chondrocyte re-distribution.  The chondrocytes outgrown into 3-D scaffolds also formed cartilage-like tissue when implanted in mice homozygous for the scid mutation (SCID mice).  Direct treatment of full-thickness chondral defects in goats using cartilage fragments on a resorbable scaffold produced hyaline-like repair tissue at 6 months.  Thus, delivery of chondrocytes in the form of cartilage tissue fragments in conjunction with appropriate polymeric scaffolds provides a novel intra-operative approach for cell-based cartilage repair

An alternative to allografting that has been proposed by some researchers is the synthetic graft.  Synthetic bone void fillers can be categorized into 3 groups:

1. ceramics,
2. composites, and
3. polymers.

Ceramics are osteo-conductive and are composed of calcium; total degradation time depends on the composition.  Composite grafts combine osteo-conductive matrix with bioactive agents that provide osteo-inductive and osteogenic properties.  Polymers are osteo-conductive and when used with marrow could provide a biodegradable osteo-inductive implant for repairing large defects.

Baker and colleagues (2011) noted that the development of synthetic bone graft substitutes is an intense area of research due to the complications associated with the harvest of autogenous bone and concerns about the supply of allogeneic bone.  Porous resorbable polymers have been used extensively in hard tissue engineering applications, but currently lack load-bearing capacity.

Vundelinckx et al (2012) reported that under arthroscopic control and guided by fluoroscopy, a TruFit Plug was successfully implanted to repair an osteochondral lesion of the head of the femur.  The procedure was evaluated clinically using the HOOS score and MRI of the hip.  The short-term (6 months) clinical results were encouraging: the HOOS score improved clearly and the patient was satisfied.  Interpretation of MRI images in the early post-operative period was very difficult: in the early months history and clinical examination prevail in the evaluation.

Joshi et al (2012) evaluated prospectively short- and medium-term results in patients with osteochondral patellar defects treated with synthetic re-absorbable scaffolds.  Patient outcome scores (Short Form 36 [SF-36] and Knee injury and Osteoarthritis Outcome Score [KOOS]), demographics, prior surgeries, and data from a physical examination were collected at baseline (before implantation) and at 6, 12, and 24 months after surgery.  Defect characteristics were collected during implantation.  Diagnosis and monitoring were performed by MRI.  A total of 10 patients with a mean age of 33.3 years (range of 16 to 49 years) were evaluated prospectively at 24 months' follow-up.  The number of plugs used for each patient ranged from 1 to 4.  At 1-year follow-up, the results were satisfactory in 8 of 10 patients, and poor in 2, according to clinical assessment (KOOS, visual analog scale, and SF-36).  At 18 months of follow-up, all patients except 1 complained of pain and knee swelling.  Re-operation rate for implant failure at final follow-up was 70 %.  Magnetic resonance imaging at final follow-up showed a cylindrical cavity of fibrous tissue instead of subchondral bone restoration.  The authors concluded that a synthetic implant can improve symptoms and joint function, especially for small lesions, only for a short period of time.  However, 2 years of monitoring has shown its failure in restoring the subchondral bone despite the formation of predominant hyaline cartilage from synthetic resorbable scaffolds.  Under current conditions and according to the authors’ experience, they do not recommend TruFit synthetic implants for osteochondral patellar defects in active patients.

Hindle et al (2014) evaluated functional outcome of patients using the EQ-5D, Knee Injury and Osteoarthritis Outcome Score (KOOS) and Modified Cincinnati scores at follow-up of 1 to 5 years.  There were 66 patients in the study (35 TruFit and 31 mosaicplasty): 44 males and 22 females with a mean age of 37.3 years (SD of 12.6).  The mean body mass index (BMI) was 26.8; 36 articular cartilage lesions were due to trauma, 26 due to osteochondritis dissecans and 3 due to non-specific degenerative change or unknown.  There were no significant differences between the 2 groups in terms of age, sex, BMI, defect location, or etiology.  The median follow-up was 22 months for the TruFit cohort and 30 months for the mosaicplasty group.  There was no significant difference in the requirement for re-operation.  Patients undergoing autologous mosaicplasty had a higher rate of returning to sport (p = 0.006), lower EQ-5D pain scores (p = 0.048) and higher KOOS activities of daily living (p = 0.029) scores.  Sub-group analysis showed no difference related to the number of cases the surgeon performed.  Patients requiring re-operation had lower outcome scores regardless of their initial procedure.  The authors concluded that the findings of this study demonstrated significantly better outcomes using 2 validated outcome scores (KOOS, EQ-5D), and an ability to return to sport in those undergoing autologous mosaicplasty compared to those receiving TruFit plugs.

Quarch et al (2014) examined if the potential donor site morbidity for large defects could be reduced by means of TruFit plugs.  An autologous OCT was performed in 37 patients and the cylinders were received from the dorsal medial femoral condyle.  The donor site defects of 21 patients (average defect size 5.5 cm(2)) were filled with artificial TruFit cylinders (study group); the donor site defects (average defect size 4.6 cm(2)) were left untreated for 16 patients.  In the study group, the Tegner, Western Ontario and McMaster Universities (WOMAC), knee society score, and visual analog scale pain scores improved from pre-operatively 3.2 (± 0.8), 60.9 (± 41.6), 133.6 (± 27.1), and 4.8 (± 2.3) points, respectively, to 3.9 (± 0.6), 35.5 (± 27.1), 177.8 (± 16.6), and 3.3 (± 2.9) points, respectively, at the time of the second follow-up; the control group's pre-operative score values came to 2.8 (± 0.9), 73.3 (± 50.2), 123.8 (± 41.5), and 5.3 (± 2.7) points, respectively, and changed to 3.6 (± 0.8), 41.4 (± 28.8), 179.3 (± 17.5), and 3.1 (± 2.0) points, respectively, at the time of the second follow-up.  The smaller the initial chondral defect was in the study group, the better the WOMAC score values became (p < 0.05).  The modified Henderson score at the study group's donor sites improved from 19.2 (± 3.3) to 13.7 (± 2.1) points (p < 0.001); the control group's score values for the donor sites were 18.3 (± 3.4) and 15.4 (± 4.4) points (p = 0.0015).  The authors concluded that OCT is an effective therapy even for large chondral defects greater than 3 cm(2).  By filling the defects with TruFit implants, no clinical improvements could be found since the donor site morbidity was already low anyway.  However, the regeneration of defects filled with TruFit implants took more than 2 years.

Gelber et al (2014) evaluated the relationship between MRI findings and functional scores of patients with osteochondral lesions of the knee treated with TruFit.  Patients were evaluated with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for MRI assessment of the repair tissue.  Knee injury and Osteoarthritis Outcome Score, SF-36 and visual analog scale (VAS) were used for clinical evaluation.  Correlation between size of the treated chondral defect and functional scores was also analyzed.  A total of 57 patients with median follow-up of 44.8 months (range of 24 to 73) were included.  KOOS, SF-36 and VAS improved from a mean 58.5, 53.9 and 8.5 points to a mean 87.4, 86.6 and 1.2 at last follow-up (p < 0.001).  Larger lesions showed less improvement in KOOS (p = 0.04) and SF-36 (p = 0.029).  Median Tegner values were restored to pre-injury situation (5, range of 2 to 10).  Mean MOCART score was 43.2 ± 16.1.  Although the cartilage layer had good integration, it showed high heterogeneity and no filling of the subchondral bone layer.  The authors concluded that TruFit failed to restore the normal MRI aspect of the subchondral bone and lamina in most cases.  The appearance of the chondral layer in MRI was partially re-established.  This unfavorable MRI appearance did not adversely influence the patient's outcome in the short-term and they restored their previous level of activity.  There was an inverse linear relationship between the size of the lesion and the functional scores.

There is currently insufficient evidence to support the safety and effectiveness of synthetic resorbable polymers as an alternative to allograft or autograft for the repair of osteochondral defects.

Vannini and colleagues (2014) stated that juvenile osteochondritis dissecans of the talus (JODT) affects the subchondral bone primarily and, in a skeletally immature population, articular cartilage secondarily.  It probably consists of aseptic bone necrosis whose spontaneous healing is impaired by micro-traumas, resulting in an osteochondral injury and, in some cases, in osteoarthritis.  In many cases the clinical presentation is asymptomatic.  Mild chronic pain is frequent, sometimes accompanied by swelling, stiffness or locking.  Few data are currently available on this topic and, moreover, most existing data were obtained from mixed groups and populations; it is therefore difficult to outline a scheme for the treatment of JODT.  However, the most suitable treatment in the first stages of the disease is conservative.  The presence of a loose body is an indication for surgical fixation, drilling or regenerative procedures, depending on the presence/extent of subchondral bone sclerosis and the surgeon's experience.  Drilling has been shown to promote the healing of lesions with minimal surgical trauma.  Micro-fractures, since they induce fibrocartilage repair, are to be considered only for small injuries.  The authors noted that mosaicplasty and osteochondral autograft transplantation may cause donor site morbidity and are techniques little reported in JODT.  Moreover, they stated that degenerative techniques and fresh allografts gave good results in osteochondral lesions, but further studies are needed to describe the results that can be obtained in JODT alone.

Hindle et al (2014) stated that autologous osteochondral mosaicplasty and TruFit bone graft substitute plugs are methods used to repair symptomatic articular cartilage defects in the adult knee.  There have been no comparative studies of the 2 techniques.  In a retrospective study, these researchers evaluated functional outcome of patients using the EQ-5D, KOOS and Modified Cincinnati scores at follow-up of 1 to 5 years.  There were 66 patients in the study (35 TruFit and 31 mosaicplasty): 44 males and 22 females with a mean age of 37.3 years (SD 12.6).  The mean BMI was 26.8; 36 articular cartilage lesions were due to trauma, 26 due to osteochondritis dissecans and 3 due to non-specific degenerative change or unknown.  There was no difference between the 2 groups in age (n.s.), sex (n.s.), BMI (n.s.), defect location (n.s.) or etiology (n.s.).  The median follow-up was 22 months for the TruFit cohort and 30 months for the mosaicplasty group.  There was no significant difference in the requirement for re-operation (n.s).  Patients undergoing autologous mosaicplasty had a higher rate of returning to sport (p = 0.006), lower EQ-5D pain scores (p = 0.048) and higher KOOS activities of daily living (p = 0.029) scores.  Sub-group analysis showed no difference related to the number of cases the surgeon performed.  Patients requiring re-operation had lower outcome scores regardless of their initial procedure.  The authors concluded that the findings of this study demonstrated significantly better outcomes using 2 validated outcome scores (KOOS, EQ-5D), and an ability to return to sport in those undergoing autologous mosaicplasty compared to those receiving TruFit plugs. This was a small study (n = 35 for TruFit) with short-term follow-up (median of 22 months for TruFit).  Well-designed studies with larger sample size and longer follow-up are needed to ascertain the clinical value of TruFit.

Guney and co-workers (2016) compared medium-term functional effects of 3 different treatment modalities in patients with osteochondral lesions of the talus (OLT). A total of 54 patients undergoing arthroscopic surgery for OLT were included in this study. Patients were assigned to 1 of the 3 treatment groups:

1. MF surgery (n = 19),
2. MF surgery plus platelet-rich plasma (PRP) (n = 22), and
3. mosaicplasty (n = 13).

Function was assessed using the American Orthopedic Foot and Ankle Society (AOFAS) scoring system and VAS scores for pain, before and after surgery.  In addition, the Foot and Ankle Ability Measure (FAAM) tests for pain and 15-min walking were done at follow-up visits.  The median duration of follow-up was 42 months (range of 12 to 84).  All groups showed significant improvements in AOFAS and VAS pain scores at the last follow-up visit, when compared to baseline.  The groups did not differ with regard to change in baseline AOFAS score; however, improvement in VAS pain scores was significantly better in the mosaicplasty group when compared to the MF group (change from baseline, -5.8 ± 1.0 versus -3.2 ± 2.9, p = 0.018).  The authors concluded that all the 3 treatment modalities resulted in good medium-term functional results.  However, they stated that mosaicplasty appeared to be a promising option and it might be preferred particularly in patients where pain control is important.

Richter and colleagues (2016) stated that isolated chondral and osteochondral defects of the knee are a difficult clinical challenge, particularly in younger patients for whom alternatives such as partial or total knee arthroplasty are rarely advised. Numerous surgical techniques have been developed to address focal cartilage defects.  Cartilage treatment strategies are characterized as palliation (e.g., chondroplasty and debridement), repair (e.g., drilling and MF), or restoration (e.g., ACI, OAT, and osteochondral allograft [OCA]).  PubMed was searched for treatment articles using the keywords knee, articular cartilage, and osteochondral defect, with a focus on articles published in the past 5 years.  In general, smaller lesions (less than 2 cm(2)) are best treated with MF or OAT. Furthermore, OAT shows trends toward greater longevity and durability as well as improved outcomes in high-demand patients.  Intermediate-size lesions (2 to 4 cm(2)) have shown fairly equivalent treatment results using either OAT or ACI options.  For larger lesions (greater than 4 cm(2)), ACI or OCA have shown the best results, with OCA being an option for large osteochondritis dissecans lesions and post-traumatic defects.  The authors concluded that these techniques may improve patient outcomes, though no single technique can reproduce normal hyaline cartilage.

Hybrid Autologous Chondrocyte Implantation (ACI) and Osteochondral Autograft Transfer System (OATS)

Duif and colleagues (2015) stated that modern orthopedic surgery provides a variety of techniques for cartilage repair.  Despite comprehensive scientific data about the single procedures, there is little experience with the combination of these methods.  These investigators performed a PubMed-based literature search about the combination of cartilage restoration principles.  The literature search was performed using the terms: "mosaicplasty'' or "osteochondral transplantation'' or "OATS'' and "autologous chondrocyte implantation'' or "autologous chondrocyte transplantation'' or "ACI'' or "matrix-associated autologous chondrocyte implantation'' or "MACI'' and "combination''.  Additionally, the authors presented a case report of the combinatory use of 3 established techniques.  Two relevant publications, both reporting satisfying results concerning post-operative functional outcome, were found.  The results confirmed this first encouraging assessment, although statistically valid data and prospective studies are still missing.  The authors concluded that the simultaneous use of different techniques for cartilage repair may provide alternative operative solutions for single complex cases, although further studies are needed for a general recommendation.

The TruFit Plug

Synthetic resorbable polymers (eg, PolyGraft, TruGraft granules, and TruFit plugs) are polymer scaffolds that are being proposed for the repair of osteochondral articular cartilage defects. The implant functions as a scaffold for chondral and osteogenic cells with the synthetic polymer being resorbed as the cells produce their normal matrices.

Verhaegen and associates (2015) stated that treatment of osteochondral defects remains a challenge in orthopedic surgery. The TruFit plug has been examined as a potential therapy for osteochondral defects.  The TruFit plug is a bi-phasic scaffold designed to stimulate cartilage and subchondral bone formation.  The authors examined clinical, radiological, and histological effectiveness of the TruFit plug in restoring osteochondral defects in the joint.  They performed a systematic search in 5 data-bases for clinical trials in which patients were treated with a TruFit plug for osteochondral defects.  Studies had to report clinical, radiological, or histological outcome data; and quality of the included studies was also assessed.  A total of 5 studies described clinical results, all indicating improvement at follow-up of 12 months compared to pre-operative status.  However, 2 studies reporting longer follow-up showed deterioration of early improvement.  Radiological evaluation indicated favorable MRI findings regarding filling of the defect and incorporation with adjacent cartilage at 24 months follow-up, but conflicting evidence existed on the properties of the newly formed overlying cartilage surface.  None of the included studies showed evidence for bone ingrowth.  The few histological data available confirmed these results.  The authors concluded that there are no data available that support superiority or equality of TruFit compared to conservative treatment or mosaicplasty / micro-fracture (MF).  They stated that further investigation is needed to improve synthetic bi-phasic implants as therapy for osteochondral lesions; RCTs comparing TruFit plugs with an established treatment method are needed before further clinical use can be supported.

Di Cave and associates (2017) noted that the TruFit plug has been investigated as a potential treatment method for osteochondral defects.  This is a bi-phasic scaffold designed to stimulate cartilage and subchondral bone formation.  In a retrospective study, these investigators examined the long-term functional and MRI outcomes of the TruFit Plug for the treatment of osteochondral lesions of the talus (OLT).  A total of 12 consecutive patients treated from March 2007 to April 2009 for OLT were evaluated.  Clinical examination included the AOFAS ankle score and the VAS for pain; MRI scans were obtained pre-treatment and at last follow-up; the MOCART score was used to assess cartilage incorporation.  Mean follow-up was 7.5 years (range of 6.5 to 8.7 years).  The average age was of 38.6 years (range of 22 to 57 years).  The sex ratio between males and females was 3:1 (9 men, 3 women).  The mean AOFAS score improved from a pre-operative score of 47.2 ± 10.7 to 84.4 ± 8 (p < 0.05).  According to the post-operative AOFAS scores, 1 case obtained excellent results, 9 were classified as good, and 2 were fair; VAS score improved from a pre-operative value of 6.9 ± 1.4 points to 1.2 ± 1.1 points at last follow-up (p < 0.05).  The MOCART score for cartilage repair tissue on post-operative MRI averaged 61.1 points (range of 25 to 85 points).  The authors concluded that the long-term results suggested that the technique of Trufit Plug for OLT was safe and demonstrated good post-operative scores including improvement of pain and function, with discordant MRI results.  Moreover, they stated that RCTs comparing TruFit Plug with an established treatment method are needed to improve synthetic bi-phasic implants as therapy for osteochondral lesions.

Bugelli and co-workers (2018) followed morphological imaging characteristics and osteo-integration of TruFit bone graft substitute (BGS) plugs in cases of chondral and osteochondral defects of the articular surface of the knee joint, using high-quality cartilage-sensitive 3-T MRI, linked to clinical outcomes.  The MRI was used to assess osteo-integration and biological evolution of the TruFit BGS plugs in cases with minimum 5-year follow-up: The TruFit plug was used in 46 patients for a total of 47 cases with mean age of 57.89 (range of 32 to 80).  In this study, these investigators reviewed only the cases with minimum follow-up of 5 years: 5 patients with mean age 64.4 years (minimum 38, maximum 80).  The mean follow-up was 71 months (range of 63 to 77).  Patients were evaluated clinically, with Lysholm Knee Scoring Scale and MOCART Scale; 3-T MRI, which was preferable to 1.5 T for the better signal-to-noise ratio, contrast and the ability to acquire morphological images at higher spatial resolution, showed a satisfactory integration of bone scaffolds in studied cases for more than 5 years and a satisfactory restoration of the articular cartilage, with the exception of a case of which these researchers still have to consider the factors of age, type of lesion and the relationship between the plugs implanted.  The authors concluded that clinical and radiological results significantly improved in a longer follow-up time.

Azam and colleagues (2018) evaluated the functional and radiological outcome of TruFit plugs; they retrospectively reviewed 10 patients who underwent treatment for a symptomatic chondral/osteochondral lesion using 1 or more Trufit Plugs.  Full incorporation of the bony portion of the plug occurred in only 3 and partial incorporation in 7 lesions.  The remaining portion of these 7 lesions looked cystic on MRI.  The significance of this cystic change was unclear.  The authors concluded that although all 10 patients showed some improvement on the IKDC scoring system, the amount of the improvement was small.

Freiberg Disease

Miyamoto and associates (2016) evaluated the mid-term clinical results of OAT for the treatment of advanced stage Freiberg disease (also known as a Freiberg infraction), which is a form of avascular necrosis in the metatarsal. This study included consecutive patients who underwent OAT for advanced stage Freiberg disease and were followed post-operatively for more than 5 years.  In all cases, the autograft was harvested from the ipsilateral knee joint.  Clinical evaluation was performed based on the AOFAS score and VAS score, which were done pre-operatively and at the most recent follow-up.  Radiological evaluation was performed at 2 years after the operation.  Furthermore, the most recent 6 patients underwent MRI 5 years after the operation to assess the configuration of the articular surface.  A total of 13 patients (all females; mean age of 16.7 years; range of 10 to 38) were included and followed-up for a mean duration of 67.2 months (range of 60 to 100). The mean AOFAS significantly improved from a score of 66.9 ± 5.3 (range of 59 to 77) to 93.0 ± 7.6 (range of 82 to 100) (p < 0.0001).  Likewise, the mean VAS significantly improved from a score of 72.7 ± 10.3 (range of 60 to 90) to 7.8 ± 7.2 (range of 0 to 20) (p < 0.0001).  Radiographs at 2 years after the operation revealed no osteoarthritic change in all cases; MRI at 5 years after the operation showed consolidation of the transplanted autograft and smooth configuration of the articular surface in the 6 cases.  The authors concluded that OAT may be effective for advanced stage Freiberg disease.  Moreover , they stated that further studies are needed before this technique can become the standard operative treatment.

Osteochondral Autograft Transfer Technique for Glenoid Osteochondral Defect

Wyland and Beicker (2016) stated that glenoid osteochondral defects can be a significant source of pain and disability in an active population.  Many treatments are available, but most joint-preserving procedures are limited to debridement, abrasion chondroplasty, or marrow-stimulation techniques, all of which depend on healthy underlying bone, and none of which addresses underlying bony pathology.  These researchers described an arthroscopic method of treating glenoid osteochondral lesions with an OAT using a graft from the patient's ipsilateral knee.  This technique addresses both cartilage and osseous pathology with minimal morbidity and provides a good biological restorative option for patients with isolated glenoid osteochondral defects.  The authors concluded that as with other glenoid cartilage restoration or preservation techniques, larger studies with longer-term follow-up are needed to evaluate this technique fully.

Minced Articular Cartilage Repair Technique

Minced cartilage repair is considered a second generation technique that does not require in-vitro cell expansion and is described as a single-staged minimally invasive procedure.  The procedure uses minced pieces of cartilage seeded over a scaffold that allows for even distribution of the chondrocytes to expand within the defect providing structural as well as mechanical protection.   The first clinical application of the minced cartilage technique was the cartilage autograft implantation system (CAIS) developed by DePuy Mitek.  A second technology, DeNOVO NT Graft ("Natural Tissue Graft"; Zimmer Inc., Warsaw, IN/ISTO Technologies Inc.) is another application for cartilage regeneration using minced donated juvenile (less than 12 years of age) fresh allograft cartilage tissue obtained from human cadavers.  Randomized trials that compare the outcomes of minced articular cartilage repair with standard methods have not been published.  Well-designed studies are needed to establish the safety and effectiveness of this approach over standard methods of cartilage repair.

Salzmann and associates (2016) stated that articular cartilage defects at the knee joint are being identified and treated with increasing frequency.  Autologous chondrocytes may have strongest potential to generate high-quality repair tissue within the defective region, in particular when large diameter defects are present.  Autologous chondrocyte implantation is not available in every country.  These researchers presented a case where they spontaneously covered an acute cartilage defect, which was significantly larger than expected and loose during initial arthroscopic inspection after reading pre-operative MRI, by mincing the separated fragment and directly implanting the autologous cartilage chips into the defective region.  The authors considered the described case as an example on how to potentially treat unexpected (and also planned), large, fresh, chondral lesions.  Moreover, they stated that high-quality, long-term studies with large patient cohorts are needed to provide better evidence.

Salzmann and colleagues (2017) presented a surgical technique where the surgeon can apply autologous chondrocytes in a 1-step procedure to treat articular cartilage defects at the knee joint.  These authors concluded that this technique can be considered as rather novel besides previous publication effort and thus several pearls/advantages as well as pitfalls/disadvantages have to be considered.  They stated that prospective and comparative long-term clinical trials with large patient cohorts (including the use of MRI) have to be performed to fully support the use of this technique.

Autologous Cartilage Chip Transplantation for Osteochondral Repair

In laboratory study using a mini-pig model, Christensen and colleagues (2017) examined in-vivo cartilage repair outcome of autologous cartilage chips (ACC) compared with marrow stimulation in full-thickness cartilage defects.  A total of 6 Gottingen mini-pigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee.  The 2 treatment groups were

1. ACC embedded in fibrin glue (n = 12), and
2. marrow stimulation (MST) (n = 12).

The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry.  Semi-quantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score.  Collagen type II staining was used to further evaluate the repair tissue composition.  Significantly more hyaline cartilage was found in the ACC (17.1 %) compared with MST (2.9 %) group (p < 0.01).  Furthermore, the ACC group had significantly less fibrous tissue (23.8 %) compared with the MST group (41.1 %) (p < 0.01).  No significant difference in fibro-cartilage content was found (54.7 % for ACC versus 50.8 % for MST).  The ACC group had significantly higher ICRS II scores for tissue morphological characteristics, matrix staining, cell morphological characteristics, surface assessment, mid/deep assessment, and overall assessment (p < 0.05).  The ACC-treated defects had significantly more collagen type II staining (54.5 %) compared with the MST-treated defects (28.1 %) (p < 0.05).  The authors concluded that ACC transplant resulted in improved quality of cartilage repair tissue compared with MST at 6 months post-operatively.  Moreover, they stated that further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

Microfracture versus Mosaicplasty / Osteochondral Autograft Transplantation (OAT) in the Treatment of Knee Articular Cartilage Defects

In a RCT, Solheim and colleagues (2018) compared the clinical outcome of microfracture versus mosaicplasty/OAT in symptomatic cartilage lesions.  The null hypothesis was that the outcome was not statistically different at any time-point.  A total of 40 patients with articular cartilage defects were randomized to undergo cartilage repair by either microfracture (n = 20) or mosaicplasty (n = 20).  Inclusion criteria were as follows: age of 18 to 50 years at the time of surgery, 1 or 2 symptomatic focal full-thickness articular chondral defects on the femoral condyles or trochlea, and size 2 to 6 cm2.  The main outcome variable was the Lysholm knee score recorded before the surgery and at 12 months, median 5 years, median 10 years, and minimum 15 years after the surgery.  Subjects included 28 men and 12 women; median age of 32 years; range of 18 to 48 years.  Defects with a median size of 3.5 cm2 (range of 2 to 5 cm2) were treated.  A significant increase in the Lysholm score was seen for all subjects – from a mean of 53 (SD, 16) at baseline to 69 (SD, 21) at the minimum 15-year follow-up (p = 0.001).  The mean Lysholm score was significantly higher in the mosaicplasty group than the microfracture group at 12 months, median 5 years, median 10 years, and minimum 15 years: 77 (SD, 17) versus 61 (SD, 22), respectively (p = 0.01), at the last follow-up.  At all follow-up time-points, the difference in mean Lysholm score was clinically significant (greater than 10 points).  The authors concluded that at short-, medium-, and long-term (minimum 15 years), mosaicplasty resulted in a better, clinically relevant outcome than microfracture in articular cartilage defects (2 to 5 cm2) of the distal femur of the knee in patients aged 18 to 50 years.  Level of Evidence = I.

In a comparative study, Solheim and colleagues (2020) examined survival of cartilage repair in the knee by microfracture (MFX; n = 119) or mosaicplasty osteochondral autograft transfer (OAT; n = 84).  For survival analyses, "failure" was defined as the event of a patient reporting a Lysholm score  of less than 65 or undergoing an ipsilateral knee replacement.  The Kaplan-Meier method was used for construction of a survival functions plot for the event "failure".  Log rank (Mantel-Cox) test was used for comparison of survival distributions in the 2 groups.  The long-term failure rate (62 % overall) was significantly higher in the MFX group (66 %) compared with the OAT group (51 %, p = 0.01).  Furthermore, the mean time to failure was significantly shorter (p < 0.001) in the MFX group, 4.0 years (SD 4.1) compared with the OAT group, 8.4 years (SD 4.8).  In the OAT group, the survival rate stayed higher than 80 % for the first 7 years, and higher than 60 % for 15 years, while the survival rate dropped to less than 80 % within 12 months, and to less than 60 % within 3 years in the MFX group, log rank (Mantel-Cox) 20.295 (p < 0.001).  The same pattern was found in a subgroup of patients (n = 134) of same age (less than 51 years) and size of treated lesion (less than 500 mm2), log rank (Mantel-Cox) 10.738 (p = 0.001).  The non-failures (48 %) were followed for a median of 15 yeas (1 to 18).  The authors concluded that MFX articular cartilage repairs failed more often and earlier than the OAT repairs, both in the whole cohort and in a subgroup of patients matched for age and size of treated lesion, indicating that the OAT repair is the more durable.  Level of evidence = III.

In a large-scale, systematic review and network meta-analysis, Zamborsky and Danisovic (2020) examined the most appropriate surgical interventions for patients with knee articular cartilage defects from the level I randomized clinical trials.  These investigators searched five databases for level I randomized clinical trials.  Treatments were compared if reported in more than 1 study using network meta-analysis to boost the number of included studies per comparison.  They studied 21 articles that included 891 patients.  Traumatic lesion was the most common cause in the included patients.  There were significantly higher failure rates in the MF group compared to ACI group at 10-year follow-up.  Moreover, OAT showed significantly more excellent or good results at greater than 3-year follow-up compared to MF, whereas MF showed significantly more poor results versus ACI and MACI.  Furthermore, OAT showed significantly more poor results than MACI at 1-year follow-up.  Similarly, patients who underwent OAT had higher return-to-activity rates than those with MF.  It should be noted that the KOOS was higher in patients who underwent characterized chondrocyte implantation or MACI compared to MF.  Finally, there were no significant differences among the various interventions regarding re-intervention, biopsy types or adverse events (AEs).  According to the p scores for interventions ranking, there was a disagreement concerning the best intervention; however, MF was always ranked as the last.  The authors concluded that cartilage repair techniques, rather than MF, provided higher quality repair of tissue and had lower failure and higher return-to-activity rates.  Moreover, OAT had significantly more excellent or good results compared to MF, whereas MF had significantly more poor results than ACI and MACI.  Moreover, these researchers stated that future studies need to have longer follow-up periods and more representative populations to examine the safety and efficacy of these interventions.

Surgical Treatment for Secondary Osteochondral Defects of the Talus

In a systematic review, Lambers and colleagues (2018) identified the most effective surgical treatment for talar osteochondral defects after failed primary surgery.  These investigators carried out a literature search to find studies published from January 1996 till July 2016 using PubMed (Medline), Embase, CDSR, DARE and CENTRAL.  Two authors screened the search results separately and conducted quality assessment independently using the Newcastle-Ottawa scale. Weighted success rates were calculated; studies eligible for pooling were combined.  A total of 21 studies (299 patients with 301 talar OCDs that failed primary surgery) were examined; 8 studies were retrospective case series, 12 were prospective case series and there was 1 RCT.  Calculated success percentages varied widely and ranged from 17 % to 100 %.  Because of the low level of evidence and the scarce number of patients, no methodologically proper meta-analysis could be performed.  A simplified pooling method resulted in a calculated mean success rate of 90 % [CI: 82 % to 95 %] for the osteochondral autograft transfer procedure, 65 % [CI: 46 % to 81 %] for mosaicplasty and 55 % [CI: 40 % to 70 %] for the osteochondral allograft transfer procedure.  There was no significant difference between classic autologous chondrocyte implantation (success rate of 59 % [CI: 39 % to 77 %]) and matrix-associated chondrocyte implantation (success rate of 73 % [CI: 56 % to 85 %]).  The authors concluded that multiple surgical treatments were used for talar OCDs after primary surgical failure.  More invasive methods were administered in comparison with primary treatment.  No methodologically proper meta-analysis could be performed because of the low level of evidence and the limited number of patients.  Thus, it was inappropriate to draw firm conclusions from the collected results.  Besides an expected difference in outcome between the autograft transfer procedure and the more extensive procedures of mosaicplasty and the use of an allograft, neither a clear nor a significant difference between therapeutic options could be demonstrated.  These researchers stated that the need for sufficiently powered prospective studies in a randomized comparative clinical setting remains high.  The findings of this systematic review could be used in order to inform patients regarding expected outcome of the various therapeutic options used after failed primary surgery.  Level of Evidence = IV.

Combination of Adipose-Derived Stem Cells and Mosaicplasty for Repair of Large Osteochondral Defects

Chen and colleagues (2019) stated that cartilage repair presents a challenge to clinicians and researchers.  A more effective procedure that can produce hyaline-like cartilage is needed for articular cartilage repair.  Mosaic osteochondral grafts for large osteochondral defects often show poor integration between the grafts and the surrounding normal cartilage, leading to defective cracks filled with fibrous tissue instead of hyaline-like cartilage.  In the present study, these researchers aimed to repair the defective cracks with a calcium alginate (CaAlg) hydrogel containing bone morphogenetic protein 4 (BMP4)-enhanced adipose-derived stem cells (ADSCs).  ADSCs were transduced with BMP4 (B-ADSCs).  The expression of BMP4 and type II collagen was confirmed using an enzyme-linked immunosorbent assay (ELISA).  Swine models of large cartilage defects of the knee were constructed and received 1 of the 4 treatments: mosaicplasty only, mosaicplasty with the CaAlg hydrogel, mosaicplasty with the CaAlg hydrogel containing ADSCs, or mosaicplasty with the CaAlg hydrogel containing B-ADSCs injected into the defective cracks.  Outcomes were evaluated at 12 and 24 weeks following surgery.  The in-vitro study showed that the osteogenic and chondrogenic activities of the B-ADSCs were enhanced compared with those of the control.  In-vivo, in the group that received mosaicplasty-containing B-ADSCs, osteochondral tissue was completely integrated with an intact surface.  Additionally, the histological scores of the mosaicplasty-containing B-ADSCs group were significantly higher than those of the other groups.  Biomechanical examination confirmed that the neocartilage possessed properties similar to those of normal cartilage.  The authors concluded that mosaicplasty and hydrogel containing B-ADSCs promoted the repair of large cartilage defects by regenerating hyaline cartilage and repairing dead spaces between osteochondral grafts and donor-site defects, thus improving the feasibility and success rate of 1-stage complete repair surgery for large osteochondral defects.  This proposed method provides a novel and effective means for the repair of large articular osteochondral defects.

Combination of Autologous Chondrocyte Implantation and Osteochondral Autograft Transfer for Repair of Large Knee Osteochondral Lesion

Kato and colleagues (2018) noted that full-thickness knee cartilage defects greater than 4 cm2 are best treated with ACI.  Since the articular cartilage surrounding the site of implantation does not always have the normal thickness desirable for successful engraftment, there may be benefit in combining ACI with OAT, which provides immediate restoration of condylar contour and mechanical function.  These researchers presented the findings of a 19-year old man who sustained a traumatic antero-lateral femoral condyle osteochondral fracture and underwent arthroscopic knee surgery 3 months after injury to harvest healthy cartilage to be sent to the Japan Tissue Engineering Co., Ltd. (J-TEC) for cartilage culture.  The patient was re-admitted after 4 weeks to undergo a procedure using the Osteochondral Autograft Transfer System (OATS) and the J-TEC autologous cultured cartilage (JACC) system.  Three 4.75-mm osteochondral cylindrical cores were harvested from non-weight-bearing areas of the knee and were transplanted to the lateral periphery of the lateral femoral condyle defect.  The cultured cartilage was implanted to the remaining defect with a periosteal cover harvested from the antero-lateral ridge of the lateral femoral condyle.  Continuous passive range of motion (ROM) exercises and gait re-training were immediately initiated, with strict no weight-bearing precaution on the operated limb.  Partial weight-bearing was allowed 4 weeks following surgery, which was progressed to full weight-bearing after another 2 weeks.  The authors concluded that ACI must be viewed as a complementary procedure to osteochondral transplantation; and this hybrid technique appeared to be a promising surgical approach and therapeutic option for large cartilage lesions, especially in the younger population.  These preliminary findings from a single-case study need to be validated by well-designed studies with larger sample size and longer follow-up (this patient was followed-up for just 1 year).

Osteochondral Autograft in the Treatment of Capitellar Osteochondritis Dissecans Lesions of the Elbow

Tsuda and co-workers (2005) reported the use of osteochondral autograft transplantation in 3 cases of non-throwing athletes with osteochondritis dissecans of the capitellum. Pre-operatively, these patients complained of elbow pain during sports activities (rhythmic gymnastics, table tennis, and basketball, respectively). Magnetic resonance imaging (MRI) showed a completely separated osteochondral fragment or a full-thickness cartilage defect. All 3 patients were treated with transplantation of an osteochondral autograft harvested from the lateral femoral condyle. They returned fully to their sports activities within 6 months of surgery. The continuity of the cartilage layer between the osteochondral graft and the capitellum was shown on MRI taken at 12 months post-operatively. The authors believed that osteochondral autograft transplantation provides successful results for non-throwing athletes with end-stage osteochondritis dissecans of the capitellum.

Shimada and associates (2005) stated that the treatment of large, advanced osteochondritis dissecans of the elbow is controversial. To determine if better results could be obtained using osteochondral autografts, these researchers retrospectively reviewed the results in 10 young athletes (mean age of 14.3 years with a range of 12 to 17 years) who were followed-up for a mean of 25.5 months (range of 18 to 45 months). After abrasion of the fragments, cylindrical osteochondral bone plugs were transferred from a lateral femoral condyle. They were evaluated clinically by the Japanese Orthopedic Association (JOA) elbow score and radiologically by radio-capitellar congruity. All patients achieved bony union in 3 months. The average JOA elbow score was 80.6 points before surgery and improved to 93.8 points at follow-up. The average percentage of radio-capitellar congruity was 35.7 % before surgery and improved to 64.2 % at follow-up. Clinical and radiological results were excellent in 8 patients and poor in 2. Poor results may be dependent on pre-existing osteoarthritis and technical difficulty related to the location of the lesion. In 8 patients, a durable load-bearing elbow was obtained with this procedure, which made hyaline-like cartilage resurfacing with healthy subchondral bony support possible. The authors concluded that osteochondral autograft is a reasonable surgical option for an advanced lesion of osteochondritis dissecans of the elbow, although long-term follow-up is needed to ascertain if the early results persist. The scientific evidence supporting the use of osteochondral autografts to repair the elbow and shoulder consists mainly of single case reports. The authors stated that currently available published studies are small, non-randomized, and lack long-term follow-up. Thus, further investigation is needed to ascertain the clinical value of osteochondral autografts for repairing  the elbow and shoulder.

In a systematic review, Logli and colleagues (2020) examined the outcomes and complications of OAT and OCA for the surgical treatment of capitellar OCD.  These investigators carried out a literature search across 3 data-bases (PubMed, Cochrane, and CINAHL [Cumulative Index to Nursing and Allied Health Literature]) from data-base inception through December 2019 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.  Individual study quality was assessed using the Methodological Index for Non-randomized Studies (MINORS) scale.  Studies were published between 2005 and 2019.  A total of 18 studies consisting of 446 elbow OCD lesions treated with OAT surgery were included.  There was a single OCA study eligible for inclusion.  Patient ages ranged from 10 to 45 years.  Of the OAT studies, 4 used autologous costal grafts whereas the remainder used autografts from the knee.  Outcome measures were heterogeneously reported.  A significant improvement in Timmerman-Andrews scores from pre-operatively to post-operatively was reported in 9 of 10 studies.  Return-to-play rates to the pre-injury level of competitive play ranged from 62 % to 100 % across 16 studies.  Significant improvement in motion, most often extension, was noted in most studies.  Reported complication, re-operation, and failure rates ranged from 0 % to 11 %, 0 % to 26 %, and 0 % to 20 %, respectively.  When used, knee autografts resulted in low donor-site morbidity (Lysholm scores, 70 to 100).  The authors concluded that OAT surgery for large, unstable OCD lesions of the capitellum reliably produced good outcomes, few complications, and a high rate of return to competitive play.  Complications were relatively uncommon, and donor-site morbidity was low.  Less was known regarding the performance of OCA given the paucity of available literature.  Level of Evidence = IV.

The authors stated that this systematic review had several drawbacks.  First, all reviews of this nature were inherently limited by the quality of evidence of their composite studies.  Although most studies included in this review were of Level IV evidence, the mean MINORS scores were reasonably good.  Heterogeneity of individual study characteristics, patients, reported outcomes, and imaging and surgical techniques was an additional drawback.  Potential areas of bias include selection of the included studies and reporting of the outcome measures in a qualitative fashion given an inability to perform formal meta-analyses.

Bae and associates (2020) stated that OATS has been advocated for unstable OCD lesions of the adolescent capitellum, although limited information is available regarding clinical and radiographic results in North American patients.  These researchers hypothesize that single-plug OATS is safe and effective in alleviating pain and restoring function in unstable OCD.  A total of 28 patients with unstable OCD treated with single-plug OATS were evaluated.  Mean age at surgery was 14.2 years; there were 14 males.  Etiology of OCD was presumed to be sports participation, including baseball (n = 5) and gymnastics (n = 11).  Indications for surgery included unstable, deep OCD lesions; 2 lesions were uncontained, and 3 patients (11% ) had OATS after failed prior surgery.  OATS was performed by an anconeus muscle-splitting approach; donor grafts were harvested from the lateral femoral condyle by small arthrotomy.  Functional outcomes were quantified using the Timmerman instrument.  Median clinical and radiographic follow-up was 6.3 months (range of 5.0 to 27.0) and 5.7 months (range of 5.0 to 26.7), respectively.  Furthermore, all patients returned functional questionnaires at a median of 9 months post-operatively (range of 5 to 27 months).  Of the 26 patients who reported pre-operative tenderness, 19 (73 %) patients had no tenderness at most recent clinical follow-up (p = 0.02).  Of 18 patients with restricted elbow motion pre-operatively, 13 had achieved full ROM (p = 0.10).  Both elbow flexion and extension improved significantly [flexion: median change (inter-quartile range [IQR]) = 10 degrees (0 to 10 degrees), p = 0.009; extension: 0 degree (-5 to 0 degrees), p < 0.001).  On post-operative MRI, 86 % (p < 0.001) of elbows had restoration of articular congruity and 93 % had complete graft incorporation.  Objective [median change (IQR) = 5 degrees (0 to 15 degrees)], subjective [25 degrees (15 to 40 degrees)], and overall [35 degrees (15 to 45 degrees)] Timmerman scores improved significantly (p = 0.001, p < 0.001, and p < 0.001, respectively).  Of the 13 patients with greater than 6 months follow-up, 9 patients (69 %) had returned to their primary sport (p = 0.27) and 100 % had returned to general sports participation.  There were no post-operative complications.  At final follow-up, all donor knees were asymptomatic with full ROM and strength.  The authors concluded that single-plug OATS was safe and effective in improving pain and elbow function in adolescents with unstable OCD, with high return to sports rates and little donor-site morbidity.  Level of Evidence = IV.

Mosaicplasty / Osteochondral Autograft in the Treatment of Osteochondral Defects of the Talus

Easley and Scranton (2003) stated that long-term outcome of the OATS procedure for osteochondral lesions of the talus is not yet available.

Aurich and colleagues (2008) noted that ankle sprains are one the most common injuries of the lower limb. Fractures, ligamentous lesions, and cartilaginous damage are often associated. Nevertheless, the injury is often mis-judged and concomitant chondral lesions are assessed late. In the case of a symptomatic osteo-cartilaginous lesion of the talus, which can be illustrated by MRI or X-ray, operative intervention is indicated. Methods such as microfracturing, mosaicplasty, and autologous chondrocyte transplantation (ACT) are in clinical use. The latter is well-known and being established as the treatment of choice for large cartilage defects in the knee. Due to the good results in the knee and the technological improvements (three-dimensional tissue constructs seeded with autologous chondrocytes) this method is being increasingly applied for cartilage lesions of the talus. In contrast to the mosaicplasty, donor site morbidity is low and the size of the defect is not a limiting factor. The current studies about ACT of the talus show a stable repair of the defect with mostly hyaline-like cartilage and high patient satisfaction. Therefore, the procedure can be recommended for lesions less than 1 cm2. Concomitant treatment of post-traumatic deformities (malalignment), ligamentous instabilities, and especially the reconstruction of bony defects are compulsory.

In a systematic review, Magnussen et al (2008) examined if ACT or osteochondral autograft transfer yields better clinical outcomes compared with one another or with traditional abrasive techniques for treatment of isolated articular cartilage defects and if lesion size influences this clinical outcome. These researchers performed a literature search and identified 5 randomized, controlled trials and 1 prospective, comparative trial evaluating these treatment techniques in 421 patients. The operative procedures included ACT, osteochondral autograft transfer, matrix-induced ACT, and microfracture. Minimum follow-up was 1 year (mean of 1.7 years; range of 1 to 3 years). All studies documented greater than 95 % follow-up for clinical outcome measures. No technique consistently had superior results compared with the others. Outcomes for microfracture tended to be worse in larger lesions. All studies reported improvement in clinical outcome measures in all treatment groups when compared with pre-operative assessment; however, no control (non-operative) groups were used in any of the studies. The authors stated that a large prospective trial investigating these techniques with the addition of a control group would be the best way to definitively address the clinical questions.

Steman and colleagues (2019) noted that OCDs of the talus are found subsequent to ankle sprains and ankle fractures.  While many surgical options are available, there is no clear evidence on return-to-sport (RTS) times and rates.  In a systematic review, these researchers summarized RTS times and rates for talar OCDs treated by various surgical techniques.  The literature from January 1996 to November 2018 was screened, and identified studies were divided into 7 different surgical treatment groups.  The RTS rate, with and without associated levels of activity, and the mean time to RTS were calculated per study.  When methodologically possible, a simplified pooling method was used to combine studies within 1 treatment group.  Study bias was assessed using the MINORS scoring system.  A total of 61 studies including 2,347 talar OCDs were included.  The methodological quality of the studies was poor.  There were 10 retrospective case series (RCSs) that examined bone marrow stimulation in 339 patients, with a pooled mean rate of RTS at any level of 88 % (95 % CI: 84 % to 91 %); 2 RCSs examining internal fixation in 47 patients found a pooled RTS rate of 97 % (95 % CI: 85 % to 99 %), 5 RCSs in which autograft transplantation was performed in 194 patients found a pooled RTS rate of 90 % (95 % CI: 86 % to 94 %), and 3 prospective case series on ACI in 39 patients found a pooled RTS rate of 87 % (95 % CI: 73 % to 94 %).  The rate of return to pre-injury level of sports was 79 % (95 % CI: 70 % to 85 %) for 120 patients after bone marrow stimulation, 72 % (95 % CI: 60 % to 83 %) for 67 patients after autograft transplantation, and 69 % (95 % CI: 54 % to 81 %) for 39 patients after ACI.  The mean time to RTS ranged from 13 to 26 weeks, although no pooling was possible for this outcome measure.  The authors concluded that different surgical options for talar OCDs allowed for adequate RTS times and rates; RTS rates decreased when considering patients' return to pre-injury levels versus return at any level.  Level of Evidence = IV.

The authors stated that this review had several drawbacks.  The 2 most important drawbacks were the high number of methodologically low-quality studies that were included and the substantial heterogeneity in the methodology of the included studies.  Heterogeneity was also observed in the used outcome measures.  Some studies reported outcomes other than the RTS rate and the mean time to RTS, reporting scores from various outcome measures instead.  Thus, not all studies could be taken into account when calculating the RTS rate and the mean time to RTS, which rendered the results of return to pre-injury level and mean time to RTS under-reported and subsequently left a possibility for the results being subject to reporting bias.  Furthermore, it was not possible to perform a formal meta-analysis.  Instead, a simplified pooling method was used for studies with the same methodology that reported outcomes after performing the same treatment technique.  As the pooled studies were all of methodologically low quality, the evidence retrieved from this simplified pooling method was based on a lower level of evidence and may contain methodological bias.  These researchers deliberately did not choose a comparative character for the present study, as RTS rates and times were highly under-reported when assessing sports outcomes, and more importantly, specific clinical indications for specific surgical therapies were highly different from one another.  Thus, it should be explicitly stated that the pooled calculated RTS rates should not be used for decision-making with respect to therapeutic options but should merely be applied to give patients an indication on the expected RTS rates and times for the different available therapeutic options.  The outcomes of the present study can therefore be utilized as a novel informative guideline on sports-specific prognosis for patients with primary and secondary talar OCDs aiming to return to (pre-injury level of) sports.

Struckmann and associates (2020) stated that talar osteochondral lesions (OCLs) lead to progressive stages of talar destruction.  Core decompression with cancellous bone grafting (CBG) is a common treatment for Berndt and Harty stages II and III.  However, in a subset of patients, talar re-vascularization may fail.  Surgical angiogenesis using vascularized medial femoral condyle (MFC) autografts may improve on these outcomes.  These 2 treatment strategies were directly compared via a prospective preliminary randomized trial including 20 subjects with talar core decompression followed by either cancellous (CBG group, n = 10) or vascularized MFC (MFC group, n = 10) bone grafting.  Outcome analysis was performed with VAS, AOFAS ankle-hindfoot score, Lower Extremity Functional Scale (LEFS), and contrast-enhanced MRI (CE-MRI) scans.  At 12 months of follow-up, the mean VAS score was reduced from 6.6 ± 2.5 pre-operatively to 4 ± 1.9 in the CBG group and from 5.2 ± 2.9 pre-operatively to 1 ± 1.1 in the MFC group (p < 0.001).  The LEFS improved from 53.4 ± 13.1 to 62.6 ± 16.2 CBG and from 53 ± 9.3 to 72.4 ± 7.4 MFC (p = 0.114).  AOFAS improved from 71 ± 12.1 to 84.1 ± 12.5 in CBG and from 70.5 ± 7.4 to 95.1 ± 4.8 in MFC (p = 0.019).  The MRI scans in the CBG group demonstrated 9 partial mal-perfusions and 1 hyper-vascularized bone graft, whereas the MFC group had 8 well-vascularized grafts incorporated into the talus and 1 partial mal-perfusion.  Vascularized MFC autografts provided superior pain relief along with improvement of physical function in patients with talar OCL stage II and III compared with CBG.  The authors concluded that to confirm these promising findings, further multi-center RCTs are needed.

Sabaghzadehand associates (2020) examined the effect of mosaicplasty on improvement of symptoms of patients with osteochondral lesions of talus.  A total of 19 patients with osteochondral lesions of talus participated in this study, who were treated with mosaicplasty.  Before and after treatment, pain (VAS), function (AOFAS), ROM and radiographic signs were evaluated.  The results of this study showed that mosaicplasty could significantly reduce pain, increase function and improve radiographic symptoms.  The ROM increased after treatment, which was non-significant.  The authors confirmed the effect of mosaicplasty on the improvement of patients with osteochondral lesions of the ankle, suggesting it as a therapeutic option.  Moreover, these researchers stated that increasing lesion size often requires more advanced regenerative or replacement techniques rather than reparative ones.  They stated that more comparative studies and RCTs are needed to ascertain which therapeutic options are more effective for certain types of lesions.

Osteochondral Autografts for the Treatment of Patellar Chondral Defects

Figueroa and colleagues (2020) noted that patellar chondral defects represent up to 34.6 % of defects found during routine arthroscopy.  Surgical management has evolved during the past 2 decades in an effort to develop techniques to replace hyaline cartilage.  At the present time, the only technique that achieves this is OAT.  Although good and excellent results have often been reported at mid-term and long-term follow-up for femoral lesions, little is known regarding isolated patellar defects.  In a retrospective, case-series study, these researchers examined clinical and imaging results of patients treated with OAT for high-grade patellar defects.  Subjects included all patients who received OAT for high-grade symptomatic patellar chondral defects between 2010 and 2018 at the authors’ institution.  The study included patients younger than 40 years of age with anterior knee pain and a grade-4 ICRS patellar chondral defect between 1 and 2.5 cm2.  Patients with surgery in other knee compartments, concomitant ACL ruptures, infection, rheumatoid arthritis, and degenerative lesions were excluded.  Six months post-operatively, all patients underwent MRI to allow assessment of graft integrity via the MOCART score to examine morphologic features and integration; WOMAC and Kujala scores were used to evaluate functional outcomes at final follow-up.  A total of 26 patients who received a patellar OAT were included.  Most patients were male (88.4 %), and the mean ± SD age was 28.5 ± 9.7 years.  Patellar chondral defects had a median size of 180 mm2 (range of 64 to 250 mm2), and patients received a median of 1 autograft (range of 1 to 3).  Functional outcomes assessed at a minimum of 1 year after surgery showed a mean Kujala score of 90.42 ± 6.7 and a mean WOMAC score of 95 ± 3.6.  MRI revealed a median MOCART score of 75 points (range of 20 to 90 points).  The authors concluded that to their knowledge, this was the largest series to-date regarding isolated patellar OAT.  At mid-term follow-up, most patients reported good and excellent results regarding symptoms and activity levels.  Most autografts showed good osseous integration and excellent filling of the chondral surface, as evidenced on MRI.  These researchers stated that OAT is a good alternative to treat high-grade patellar chondral defects, especially among young patients.  Moreover, they stated that further prospective, mid-term and long-term follow-up studies are needed to corroborate these findings, but this study provided promising results for treating surgeons. Level of Evidence = IV.

The authors stated that this study had several drawbacks.  Results could be attributable to the retrospective nature of this analysis.  These investigators did not carry out pre-operative assessment of functional scores to compare with pre-operative scores; thus, they were unable to state the magnitude of the improvement from this procedure.  In addition, more than 50 % of the subjects had concomitant surgery to correct patellar instability, which may have influenced the results.  Furthermore, these findings could be influenced by the relatively small sample size (n = 26).

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
27416	Osteochondral autograft(s), knee, open (eg, mosaicplasty) (includes harvesting of autograft[s]) [except to repair chondral defects of the patella] [excludes synthetic resorbable polymers]
29866	Arthroscopy, knee, surgical; implantation of osteochondral autograft(s) (e.g., mosaicplasty) (includes harvesting of autografts) [except to repair chondral defects of the patella] [excludes synthetic resorbable polymers]
CPT codes not covered for indications listed in the CPB:
Autologous cartilage chip transplantation - no specific code :
27412	Autologous chondrocyte implantation, knee
28446	Open osteochondral autograft, talus (includes obtaining graft(s)) [excludes synthetic resorbable polymers]
Other CPT codes related to the CPB:
27447	Arthroplasty, knee, condyle and plateau; medial AND lateral compartments with or without patella resurfacing (total knee arthroplasty)
29871	Arthroscopy, knee, surgical; for infection, lavage and drainage
29874	for removal of loose body or foreign body (e.g., osteochondritis dissecans fragmentation, chondral fragmentation)
29877	debridement/shaving of articular cartilage (chondroplasty)
29879	abrasion arthroplasty (includes chondroplasty where necessary) or multiple drilling or microfracture
29885	drilling for osteochondritis dissecans with bone grafting, with or without internal fixation (including debridement of base of lesion)
29886	drilling for intact osteochondritis dissecans lesion
29887	drilling for intact osteochondritis dissecans lesion with internal fixation
HCPCS codes covered if selection criteria are met:
J7330	Autologous cultured chondrocytes, implant [except minced articular cartilage (whether synthetic, allograft or autograft)]
S2112	Arthroscopy, knee, surgical, for harvesting of cartilage (chondrocyte cells)
HCPCS codes not covered for indications listed in the CPB (not all inclusive):
Minced articular cartilage, synthetic, allograft or autograft:
No specific code
ICD-10 codes covered if selection criteria are met:
M23.000 - M23.92	Internal derangement of knee [articular cartilage defect]
M25.161 - M25.169	Fistula, knee [articular cartilage of knee]
M25.861 - M25.869	Other specified joint disorders, knee [articular cartilage of knee]
M92.40 - M92.52	Juvenile osteochondrosis of lower extremity [excluding foot]
M92.8	Other specified juvenile osteochondrosis [leg] [articular cartilage of knee]
M93.261 - M93.269	Osteochondritis dissecans knee
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
M21.861 - M21.869	Other specified acquired deformities of lower leg [non-correctable varus or valgus deformities]
M24.111 - M24.129	Other articular cartilage disorders, shoulder and elbow
M24.151 - M24.176	Other articular cartilage disorders, hip, ankle & foot
M25.151 - M25.159 M25.171 - M25.176	Fistula of hip and ankle & foot
M25.251 - M25.259 M25.271 - M25.279	Flail joint, hip and ankle & foot
M25.351 - M25.359 M25.371 - M25.376	Other instability, hip and ankle & foot
M25.851 - M25.859 M25.871 - M25.879	Other specified joint disorders, hip and ankle & foot
M91.0 - M91.92	Juvenile osteochondrosis of hip and pelvis
M92.00 - M92.32	Juvenile osteochondrosis of upper extremity
M92.60 - M92.72	Juvenile osteochondrosis of foot

The above policy is based on the following references: