Fig 1

Fig. 1

Flowchart outlining the systematic review.

Fig 2

Fig. 2

Treatment recommendations per joint and lesion size.

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Abstract

Background

Cartilage defects are treated with a wide array of non-operative and surgical procedures. Optimal choice of treatment depends on lesion depth and size.

Objectives

To review and summarize current data on the management of cartilage injuries in joints as it relates to defect size.

Data sources

MEDLINE, Cochrane Central Register of Controlled Trials & Cochrane Library, CINHAL.

Study eligibility criteria, participants, and interventions

Inclusion: (1) Studies investigating patients who underwent cartilage repair of the shoulder, elbow, hip, knee, and ankle. (2) Studies reporting outcome measures and treated lesion size. Exclusion: (1) No mention of defect size. (2) Joints not mentioned above. (3) <12 months clinical follow-up. (4) Unavailable full English or full texts.

Study appraisal and synthesis methods

Selection procedure and homogeneity of patient population and preoperative and postoperative care were examined. Attrition bias was scored based on the percentage follow-up of the primary outcome parameter. Level of evidence was determined according to the guidelines of the Oxford Center for Evidence-Based Medicine.

Results

Small lesions sized 1.5 cm2 are often either fixated or conservatively treated, lesions sized >1.5 cm2 mostly addressed with cell-based therapies such as autologous cartilage implantation (ACI), or matrix associated cartilage implantation (MACI). Large lesions often are the domain of osteochondral autograft transfer system (OATS).

Limitations

Prospective randomized controlled studies are not available for every joint and many studies represent case studies with limited implications for treatment decisions.

Conclusions and implications of key findings

Evidence-based treatment selection based on cartilage defect size can be beneficial.

Systematic review registration number

276559.

Introduction

Cartilage lesions in large joints are common and can occur in isolation or in combination with bone deficiencies, ligament injuries, limb malalignment, and traumatic, concomitant injuries. Each of these potential pathologies must be addressed to achieve a successful outcome for any cartilage restoration procedure. Focal cartilage defects result in disability that can be similar to osteoarthritis (OA).1x1Krych, A.J. et al. Cartilage injury in the knee: assessment and treatment options. J Am Acad Orthop Surg. 2020; 28: 914–922

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The size of the lesions is a determining factor in every algorithm of decision making in terms of treatment.2x2Ramponi, L. et al. Lesion size is a predictor of clinical outcomes after bone marrow stimulation for osteochondral lesions of the talus: a systematic review. Am J Sports Med. 2017; 45: 1698–1705

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The decision if a cartilage lesion demands surgical treatment is depending on a variety of parameters and should always be reached mutually between physician and patient after thorough education about risks and benefits of operative and conservative treatment options. Radiographs are often unrevealing in patients with acute joint pain after a cartilage injury. Indirect signs, such as an effusion or a loose body may be noted, but magnetic resonance imaging (MRI) is the preferred imaging modality to evaluate the depth, size, and location of cartilage lesions and subchondral bone involvement. With the broad availability of high resolution, multiplanar imaging, the diagnosis and treatment of cartilage pathologies have improved. Chondropathologies can be identified earlier in their natural progression, increasing opportunities for treatment and preservation prior to onset of degenerative changes.3x3Hwang, D.S. and Noh, C.K. Comprehensive review of advancements in hip arthroscopy. Hip Pelvis. 2017; 29: 15–23

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Lesion classification is of high clinical importance in determining the right treatment option. While the Outerbridge Classification, published in 1961, takes the lesion size into consideration (Grade 2: partial thickness lesions 〈1.5 cm in diameter; Grade 3: lesions 〉1.5 cm in diameter or full thickness), the widely used International Cartilage Repair Society Classification (ICRSC) combines size and depth to better characterize and describe defects.4x4Slattery, C. and Kweon, C.Y. Classifications in brief: outerbridge classification of chondral lesions. Clin Orthop Relat Res. 2018; 476: 2101–2104

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The term cartilage lesion used in this article refers to both, solitary chondral lesions (ICRS grade 1-3) and chondral lesions with affection of the subchondral bone (ICRS grade 4).

Joint preservation is the preferred treatment strategy for chondropathologies of the large joints in young and active patients in order to improve pain, restore activity, and prevent the progression of degenerative changes. Given the relatively recent emergence of the field, so far, there remains a paucity of research regarding available treatment data and results as they relate to cartilage defect size. Apart from the knee, only limited high-quality data is available to provide guidance in treatment decisions for other joints.

In this review, we focus on the primary surgical treatment options for small cartilage defects defined as those less than 1.5 to 3 cm,2x2Ramponi, L. et al. Lesion size is a predictor of clinical outcomes after bone marrow stimulation for osteochondral lesions of the talus: a systematic review. Am J Sports Med. 2017; 45: 1698–1705

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depending on the joint affected. Additionally, we describe the upper limit of defect sizes that are treatable with reconstructive techniques.

Objectives

The purpose of this review is to assess and review available evidence for cartilage repair depending on the size of the lesion and thus help inform patients and surgeons about treatment strategies in this evolving field. We aim to illustrate the lower limit of defect sizes that need to be repaired in order to maintain joint integrity as well as the upper limit of lesion sizes that can and should be surgically addressed with today's available joint preservation procedures.

Material and methods

Literature search

A comprehensive literature search was conducted on May 25, 2021 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Fig. 1). Queried databases included MEDLINE, the Cochrane Central Register of Controlled Trials & Cochrane Library, and CINHAL (Cumulative Index for Nursing and Allied Health Literature). No date search period parameters were set, and a Boolean algebra search strategy was utilized as follows: (Cartilage OR chondral) AND (Defect OR lesion) AND (size) AND (Shoulder OR elbow OR hip OR knee OR ankle). Articles were catalogued using Microsoft Excel (Version 16.50; 2021; Microsoft Corp). Duplicate articles, systematic reviews, in vitro studies, and non-English articles were eliminated. Abstracts of these studies were then manually reviewed by 1 author and studies not related to the research topic were removed from the list. Full texts were then retrieved and manually reviewed for inclusion. In addition, reference lists and prior studies for reviewed studies were also reviewed for any potential missed inclusions.

Fig 1 Opens large image

Fig. 1

Flowchart outlining the systematic review.

Inclusion criteria

  • (1)

    Studies investigating patients who underwent cartilage repair of the shoulder, elbow, hip, knee, and ankle.

  • (2)

    Studies reporting outcome measures and treated lesion size.

Exclusion criteria

  • (1)

    Studies reporting on cartilage repair without mention of the treated defect size.

  • (2)

    Studies reporting on cartilage repair of other joints than those mentioned above.

  • (3)

    Studies reporting with less than 12 months of clinical follow-up.

  • (4)

    Studies with unavailable full English texts.

  • (5)

    Studies with unavailable full texts.

Seventy-four studies were identified and analyzed according to the above criteria (Fig. 1). Articles were reviewed by the senior authors until a consensus was reached regarding inclusion.

To determine the possibility of bias, we examined the selection procedure (selection bias) and homogeneity of the patient population and preoperative and postoperative care (performance bias). Attrition bias was scored based on the percentage follow-up of the primary outcome parameter. Possible detection bias was quantified by blinding of observers, validity of outcome measures, and the statistical analysis, whereas reporting bias was assessed by differences in description of outcome parameters between the study groups. Level of evidence (LOE) was determined according to the guidelines of the Oxford Center for Evidence-Based Medicine. After this evaluation, articles were selected based on the risk of bias, modified Coleman score, on PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and LOE to answer our clinical research question.

Data were collected from articles meeting inclusion and exclusion criteria. Subsequently extracted data included authors, year of publication, journal of publication, surgical procedures analyzed, number of patients, mean age, gender, main inclusion criteria, defect location, defect size, and defect grade. Primary and secondary outcomes as well as follow-up information were recorded on standardized forms for this systematic review.

Assessment of level of evidence

Two independent reviewers evaluated each study and created a classification based on the level of evidence (LOE) using previously published criteria.5x5Marx, R.G., Wilson, S.M., and Swiontkowski, M.F. Updating the assignment of levels of evidence. J Bone Joint Surg Am. 2015; 97: 1–2

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Assessment of quality of evidence

The quality of evidence of the included studies was assessed using the Modified Coleman Methodology Score (MCMS) (Table X). The Coleman Methodology Score was initially described to evaluate the quality of studies investigating the treatment of tendinopathy.6x6Coleman, B.D. et al. Studies of surgical outcome after patellar tendinopathy: clinical significance of methodological deficiencies and guidelines for future studies. Victorian institute of sport tendon study group. Scand J Med Sci Sports. 2000; 10: 2–11

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This score includes part A (primarily evaluates baseline study characteristics; 0-60) and part B (primarily evaluates outcome criteria and recruitment rates; 0-40) and was subsequently modified by Jakobsen et al for the assessment of cartilage repair.7x7Jakobsen, R.B., Engebretsen, L., and Slauterbeck, J.R. An analysis of the quality of cartilage repair studies. J Bone Joint Surg Am. 2005; 87: 2232–2239

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Two independent reviewers determined the MCMS for each study. If any discrepancy existed, all available data was reviewed, and a consensus was reached. Excellent studies scored 85 to 100, good studies scored 70 to 84, fair studies scored 55 to 69, and poor studies scored less than 55.7x7Jakobsen, R.B., Engebretsen, L., and Slauterbeck, J.R. An analysis of the quality of cartilage repair studies. J Bone Joint Surg Am. 2005; 87: 2232–2239

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Results

After a full-text review,74x74Saris, D. et al. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: two-year follow-up of a prospective randomized trial. Am J Sports Med. 2014; 42: 1384–1394

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studies were identified for inclusion in the current study (Fig. 1).

Level of evidence

There were 12 studies of LOE 1, 11 studies LOE 2, 10 studies of LOE 3, 30 studies of LOE 4 and 7 studies of LOE 5. Although 1 study was described as LOE 1 in the published journal, this article was reassigned as LOE 2 in the current study based on the previously published criteria.8x8Gobbi, A. et al. Osteochondral lesions of the talus: randomized controlled trial comparing chondroplasty, microfracture, and osteochondral autograft transplantation. Arthroscopy. 2006; 22: 1085–1092

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Quality of evidence

The mean MCMS of the overall population of the studies was 63.4 ± 19.6 of 100 points. The mean MCMS in part A and part B were 39.3 ± 11.1 and 24.1 ± 11.0, respectively.

Shoulder

The shoulder joint's function relies primarily on soft tissue structures to provide well-balanced and centered movement about the central axis of the joint. As long as the joint is centered, smaller cartilage defects are relatively asymptomatic, as the shoulder is subjected to relatively modest point-loading demands. In comparison, substantially higher forces are distributed throughout large portions of the joint surface of the hip, knee, and ankle.9x9Saltzman, B.M., Leroux, T., and Cole, B.J. Management and surgical options for articular defects in the shoulder. Clin Sports Med. 2017; 36: 549–572

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Isolated, full-thickness chondral lesions of the glenohumeral joint are a clinically significant pathology encountered by laborers, athletes, and the elderly as they tend to enlarge over time.10x10Slabaugh, M.A., Frank, R.M., and Cole, B.J. Resurfacing of isolated articular cartilage defects in the glenohumeral joint with microfracture: a surgical technique & case report. Am J Orthop (Belle Mead NJ). 2010; 39: 326–332

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While the incidence of such lesions is 5% to 17% and therefore much lower than in the hip and knee, the natural history of full-thickness chondral lesions in the shoulder is less clearly described than those of the knee or ankle.11x11Frank, R.M. et al. Clinical outcomes after microfracture of the glenohumeral joint. Am J Sports Med. 2010; 38: 772–781

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The glenohumeral joint cartilage is relatively thin, not exceeding more than 2 mm at the central articulating surface of the humerus and becoming thinner towards the joint periphery.12x12Cole, B.J., Yanke, A., and Provencher, M.T. Nonarthroplasty alternatives for the treatment of glenohumeral arthritis. J Shoulder Elbow Surg. 2007; 16: S231–S240

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Siebold et al adopted the microfracture technique established in the knee and performed it on 5 patients with Outerbridge grade IV lesions of the humeral head with a mean size of 3.11 cm².13x13Siebold, R., Lichtenberg, S., and Habermeyer, P. Combination of microfracture and periostal-flap for the treatment of focal full thickness articular cartilage lesions of the shoulder: a prospective study. Knee Surg Sports Traumatol Arthrosc. 2003; 11: 183–189

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They reported favorable clinical and radiologic results at a mean of 26 months follow-up. Three patients underwent a second look arthroscopy and demonstrated a size reduction of the cartilage defect. Of note, 2 other patients did show signs of joint degeneration on radiographs at final follow-up.

Millett et al performed microfracture for symptomatic full-thickness cartilage defects of the glenohumeral joint in 30 patients with a mean lesion size of 3.07 cm² and a range of 1 to 14 cm².14x14Millett, P.J., Huffard, B.H., Horan, M.P. et al. Outcomes of full-thickness articular cartilage injuries of the shoulder treated with microfracture. Arthroscopy. 2009; 25: 856–863

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Here, 24 patients reported significant improvements in patient-reported outcome scores at a mean follow-up of 47 months. While 6 patients progressed to further surgery, a negative correlation between the size of cartilage defect and ASES score was observed. This finding supports the use of microfracture in small-sized lesions.15x15Erggelet, C. and Vavken, P. Microfracture for the treatment of cartilage defects in the knee joint - a golden standard?. J Clin Orthop Trauma. 2016; 7: 145–152

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Another non-randomized, non-controlled trial was published by Frank et al who reported of 16 patients who underwent arthroscopic microfracturing of the humeral head and/or the glenoid surface.11x11Frank, R.M. et al. Clinical outcomes after microfracture of the glenohumeral joint. Am J Sports Med. 2010; 38: 772–781

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The average diameter of the chondral lesions treated was 19.7 ± 4.9 mm (range, 10-25) overall, 20.8 ± 2.9 mm (range, 15-25) humeral, and 16.3 ± 3.7 mm (range, 10-20) on the glenoid. At a mean follow-up time of 28 months, a significant decrease in pain after surgery and a significant improvement in clinical outcomes were reported. 3 patients did go on to have further surgery during follow-up.

While there is no published defect size limit for microfracture in the shoulder, as is quoted consistently through the knee literature, microfracture in the shoulder is generally indicated for smaller sized lesions up to a size of 2 cm2, while midsized defects of the humeral head can be addressed with Autologous Chondrocyte Implantation (ACI).14x14Millett, P.J., Huffard, B.H., Horan, M.P. et al. Outcomes of full-thickness articular cartilage injuries of the shoulder treated with microfracture. Arthroscopy. 2009; 25: 856–863

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,16x16Boehm, E., Minkus, M., and Scheibel, M. Autologous chondrocyte implantation for treatment of focal articular cartilage defects of the humeral head. J Shoulder Elbow Surg. 2020; 29: 2–11

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ACI comprises a 2-step procedure: Chondrocytes are biopsied from a donor joint surface, expanded, and applied underneath a periosteal patch (ACI) or applied and implanted on a membrane (MACI; matrix-induced autologous chondrocyte implantation). Boehm et al recently reported on 7 patients who underwent ACI for symptomatic focal grade IV cartilage lesions of the humeral head with a median size of 3 cm² (range 2.3-4.5 cm2). At mean follow-up time of 32 months, the subjective shoulder value improved to 95% compared to 60% preoperatively.16x16Boehm, E., Minkus, M., and Scheibel, M. Autologous chondrocyte implantation for treatment of focal articular cartilage defects of the humeral head. J Shoulder Elbow Surg. 2020; 29: 2–11

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Postoperative median Constant score and ASES were 95-97 points, respectively. However, the authors concluded that the procedure is, in consideration of its 2-stage surgical design and the cost intensiveness, restricted to young and active patients in their practice. As of today, the procedure is only approved for use in the knee by the US Federal Drug Administration (FDA) and European Medicines Agency. Another treatment option, particularly for large defects, is osteochondral allograft transplantation (OCA). Camp et al reported a transplantation of a tibial osteochondral allograft to restore a large glenoid osteochondral defect that resulted in a significant improvement in both, QuickDASH and ASES score at 12 months follow-up.17x17Camp, C.L., Barlow, J.D., and Krych, A.J. Transplantation of a tibial osteochondral allograft to restore a large glenoid osteochondral defect. Orthopedics. 2015; 38: e147–e152

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Kircher et al reported 9 years results of osteochondral autologous transplantation for the treatment of full-thickness cartilage defects of the shoulder.18x18Kircher, J. et al. Osteochondral autologous transplantation for the treatment of full-thickness cartilage defects of the shoulder: results at nine years. J Bone Joint Surg Br. 2009; 91: 499–503

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The mean defect size treated was relatively small with 1.5 cm² and it was a mean of 1.86 osteochondral cylinders used. 100% of the patients were subjectively very satisfied. No reoperations were reported, and the Mean Constant score improved from 76.2 to 90.9.

While randomized controlled trials are lacking, the available literature suggests that lesions of the glenoid and humerus 1.5 cm2 and greater can successfully be addressed with cartilage repair and short- to midterm improvement in pain function can be expected. In general, evidence is limited and the use of cartilage repair techniques in the shoulder lacks standardization regarding location and size of the defect, resulting in variable indications for similar defects. Table 1 summarizes the available evidence.

Table 1Shoulder.
StudyJournalYearLevelEnrolled participantsLesion size (cm²)Age (years)TreatmentOutcome parameterFollow-up time (months)Results
Siebold et alKnee Surg Sports Traumatol Arthrosc2003IV53.1132Mfx + periostal flapMRI; X-rays; Constant score; Second look arthroscopy25.8CS improved significantly; MRI: layer of regeneration tissue; Arthroscopy: Significant reduction of cartilage lesion
Millett et alArthroscopy2009IV303.0745.5MfxASES; Patient satisfaction45Significant improvement in ASES; High patient satisfaction
Frank et alAm J Sports Med2010IV165.0737MfxSST; ASES; VAS27.8Significant improvements in SST and ASES; Decrease in VAS
Buchmann et alJ Shoulder Elbow Surg2012IV4429.3ACIVAS; ASES; MRI; CS41.3Significant improvements in SST and ASES; Decrease in VAS; MRI with satisfactory defect coverage with signs of fibrocartilaginous repair tissue
Camp et alOrthopedics2015V1625OCASSV; ASES; QuickDASH12Significant improvement in ASES and SSV; Improved ROM
Boehm et alJ Shoulder Elbow Surg2020IV7342.8ACISSV; ASES32Significant improvement in ASES and SSV
View Table in HTML

Abbreviations: ACI, autologous chondrocyte implantation; ADL, activities of daily living; ASES, American shoulder and elbow surgeons; MRI, Magnetic resonance imaging; OA, osteochondral allograft; OATS, osteochondral autograft transplantation system; OCA, osteochondral allograft transplantation; ROM, range of motion; SST, simple shoulder test; SSV, subjective shoulder value; VAS, visual analog scale.

Elbow

Most cartilage injuries of the capitellum are found in the context of osteochondritis dissecans (OCD). While first coined by Koenig in 1888, the specific pathophysiological mechanism for the development of OCD remains unclear.19x19Konig, F. The classic: on loose bodies in the joint. 1887. Clin Orthop Relat Res. 2013; 471: 1107–1115

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A multi-factorial etiology consisting of repetitive microtrauma, localized ischemia, genetic predisposition, and altered biomechanics is currently thought to cause this disease process.20x20Camp, C.L. et al. Arthroscopic microfracture for osteochondritis dissecans lesions of the capitellum. Arthrosc Tech. 2016; 5: e477–e481

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In young patients with open physes, around 95% of the lesions may heal without surgical intervention.21x21Mihara, K. et al. Nonoperative treatment for osteochondritis dissecans of the capitellum. Am J Sports Med. 2009; 37: 298–304

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This number is decreased to 50% in patients with closed physes. Indications for surgery include (1) failure of conservative management, (2) unstable lesions, (3) presence of mechanical symptoms and/or loose bodies, and (4) pain in the context of daily activities. While small lesions can often undergo internal fixation with historically good outcomes, larger lesion sizes of greater than 10 to 12 mm in diameter or 50% of the capitellar articular surface are commonly treated with restorative procedures such as osteochondral autograft transfer (OAT) or osteochondral allograft transplantation.20x20Camp, C.L. et al. Arthroscopic microfracture for osteochondritis dissecans lesions of the capitellum. Arthrosc Tech. 2016; 5: e477–e481

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,22x22Uchida, S. et al. Arthroscopic fragment fixation using hydroxyapatite/poly-l-lactate Acid thread pins for treating elbow osteochondritis dissecans. Am J Sports Med. 2015; 43: 1057–1065

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Stage II and III lesions with a diameter of up to 10 mm and an intact lateral pillar can be treated with microfracture. Lewine et al reported on 21 patients who underwent microfracture for such lesions. While there were no revisions, 85.7% of patients returned to any sport, whereas 66.7% returned to their primary sport at the mean time of follow-up of 2.3 years. Range of motion and Timmerman scores improved significantly.23x23Lewine, E.B. et al. Early results of drilling and/or microfracture for grade IV osteochondritis dissecans of the capitellum. J Pediatr Orthop. 2016; 36: 803–809

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Regarding larger lesions, Iwasaki et al reported on 19 baseball players who underwent OATs for defects averaging 1.47 cm2 at a mean follow-up of 45 months and found statistically significant improvements in Timmerman and Andrews (T&A) scores, elbow motion, pain relief (95% of patients), and a 90% return to play rate, indicating that the repair of small lesions can result in substantial clinical benefits.24x24Iwasaki, N. et al. Autologous osteochondral mosaicplasty for osteochondritis dissecans of the elbow in teenage athletes: surgical technique. J Bone Joint Surg Am. 2010; 92: 208–216

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While OATs has demonstrated encouraging short- and mid-term results, some patients and parents may have reservations towards a harvesting procedure on a healthy, asymptomatic knee or other donor site. Given this, OCA may provide an attractive alternative as grafts can be obtained from cadaveric femoral condyles or capitella, albeit with increased associated graft costs. Early results of OCA use in the elbow have been promising.25x25Mirzayan, R. and Lim, M.J. Fresh osteochondral allograft transplantation for osteochondritis dissecans of the capitellum in baseball players. J Shoulder Elbow Surg. 2016; 25: 1839–1847

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Mirzayan et al reported results of the treatment of 9 male baseball players with OCD of the capitellum, that were treated with an average plug diameter of 11 mm. At a mean follow-up of 48 months, Mayo Elbow Performance score improved from an average of 57.8 preoperatively to 98.9.25x25Mirzayan, R. and Lim, M.J. Fresh osteochondral allograft transplantation for osteochondritis dissecans of the capitellum in baseball players. J Shoulder Elbow Surg. 2016; 25: 1839–1847

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In summary, cartilage repair and restoration techniques of the elbow include microfracture, OATs, OCA, and ACI.26x26Patzer, T., Krauspe, R., and Hufeland, M. Arthroscopic autologous chondrocyte transplantation for osteochondritis dissecans of the elbow. Arthrosc Tech,. 2016; 5: e633–e636

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, 27x27Iwasaki, N. et al. Transplantation of tissue-engineered cartilage for the treatment of osteochondritis dissecans in the elbow: outcomes over a four-year follow-up in two patients. J Shoulder Elbow Surg. 2010; 19: e1–e6

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Microfracture is often indicated in patients with ICRS stage II and III and a lesion with a diameter of up to 10 mm20. Lesions sized greater than 10 to 12 mm in diameter are usually addressed with restorative procedures such as OAT or OCA.28x28Shimada, K. et al. Cylindrical costal osteochondral autograft for reconstruction of large defects of the capitellum due to osteochondritis dissecans. J Bone Joint Surg Am. 2012; 94: 992–1002

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In the case of deficient or necrotic subchondral bone or large subchondral cysts, even small lesions are treated with structural reconstructive techniques (OATs and OCA), as reparative procedures are incapable of rebuilding the supportive bone stock necessary to support a stable cartilage bed.29x29Zlotolow, D.A. and Bae, D.S. Osteochondral autograft transplantation in the elbow. J Hand Surg Am. 2014; 39: 368–372

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An overview of current evidence in the elbow is summarized in Table 2.

Table 2Elbow.
StudyJournalYearLevelEnrolled participantsLesion size (cm²)Age (years)TreatmentOutcome parameterFollow-up timeResults
Jones et alJ Pediatr Orthop2010IV25not reported13.1BMSSANE, ROM48Significant improvement in SANE and ROM
Wulf et alAm J Sports Med2012IV10not reported13.9MfxMEPS, ROM42Significant improvement in MEPS and ROM
Maruyama et alAm J Sports Med2014IV332.2413.6OATSTaA, ROM, RTS, Rx28.4Significant improvement in TaA and ROM, Complete incorporation of grafts in Rx, 93.9% RTS
Lyons et alJ Shoulder Elbow Surg2015IV11>1 cm²14.5OATSDASH, ROM22.7Significant improvement in DASH and ROM
Uchida et alAm J Sports Med2015IV18not reported14.2Fragment
pin
refixationMEPS, ROM39Significant improvement in MEPS and ROM
Mirzayan et alJ Shoulder Elbow Surg2016IV9not reported15.3FOCATMEPS, OES, DASH, VAS, ROM48.4Significant improvement in all scores and ROM
View Table in HTML

Abbreviations: ACI, autologous chondrocyte implantation; ADL, activities of daily living; ASES, American shoulder and elbow surgeons; BMS, Bone marrow stimulation; FOCAT, fresh osteochondral allograft transplantation; MEPS, mayo elbow performance score; Mfx, microfracture; OA, osteochondral allograft; OATS, osteochondral autograft transplantation system; OES, oxford elbow score; ROM, range of motion; RTS, return to sport; Rx, radiographs; SANE, single assessment numerical evaluation; TaS, Timmerman and Andrews score; VAS, visual analog scale.

Hip

The hip joint is a ball and socket synovial joint and similar to the big lower extremity joints, a major weight-bearing joint, only secondary to the knee, and amongst the largest bony articulations in the body. It plays a central biomechanical role in locomotion, while transferring the weight of the body from the axial skeleton into the lower extremities, placing high stress on the articulating cartilage surfaces of the main load carrying areas of the femoral head and the acetabulum. Even small chondral or subchondral pathologies can lead to potentially symptomatic cartilage damage, that can initiate the development of OA.30x30Murphy, N.J., Eyles, J.P., and Hunter, D.J. Hip osteoarthritis: etiopathogenesis and implications for management. Adv Ther. 2016; 33: 1921–1946

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Hip related pain is a common cause for presentation in orthopedic clinics, with an estimated annual incidence of 440 per 100,000 people in the general population aged 15 to 60 years.31x31Roling, M.A., Mathijssen, N.M., and Bloem, R.M. Incidence of symptomatic femoroacetabular impingement in the general population: a prospective registration study. J Hip Preserv Surg. 2016; 3: 203–207

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In the cohort of patients who present with mechanical hip symptoms, up to 76% are subsequently diagnosed with (osteo)chondral lesions of the hip joint.32x32Neumann, G. et al. Prevalence of labral tears and cartilage loss in patients with mechanical symptoms of the hip: evaluation using MR arthrography. Osteoarthritis Cartilage. 2007; 15: 909–917

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Damage to the hip cartilage can lead to severe disabilities, onset and progression of OA, and ultimately to the need for total hip arthroplasty.33x33Ganz, R. et al. Femoroacetabular impingement: a cause for osteoarthritis of the hip. Clin Orthop Relat Res. 2003; : 112–120

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Given the poor regenerative properties of cartilage and the high load environment of the joint, early intervention and treatment of defects is paramount in the prevention of OA and the preservation of joint function. Due to the biomechanical relationship between a cam morphology of the femoral neck and resulting cartilage damage to the chondrolabral junction, the most common location for defects is the anterosuperior acetabulum.32x32Neumann, G. et al. Prevalence of labral tears and cartilage loss in patients with mechanical symptoms of the hip: evaluation using MR arthrography. Osteoarthritis Cartilage. 2007; 15: 909–917

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,34x34McCarthy, J.C. and Lee, J.A. Arthroscopic intervention in early hip disease. Clin Orthop Relat Res. 2004; : 157–162

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In contrast, femoral lesions are most often found centrally located in the head.32x32Neumann, G. et al. Prevalence of labral tears and cartilage loss in patients with mechanical symptoms of the hip: evaluation using MR arthrography. Osteoarthritis Cartilage. 2007; 15: 909–917

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Hip cartilage plays partially different and more extensive roles than cartilage in other joints. The concave hip articular surface provides constraint and stability, whereas the knee is aligned by ligaments and menisci, holding together joint surfaces that are otherwise not inherently constrained. The loss of joint stability and onset of cartilage degeneration in cases of acetabular fractures involving as little as 20% of the posterior wall surface, highlights the importance of hip articular surface in providing stability.35x35Dangin, A. et al. Microinstability of the hip: a review. Orthop Traumatol Surg Res. 2016; 102: S301–S309

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, 36x36Woodward, R.M. et al. Microinstability of the hip: a systematic review of the imaging findings. Skeletal Radiol. 2020; 49: 1903–1919

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, 37x37Firoozabadi, R. et al. Determining stability in posterior wall acetabular fractures. J Orthop Trauma. 2015; 29: 465–469

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Additionally, the labrum plays a key biomechanical role in providing hip stability and maintaining physiologic chondral loading. This is illustrated by the high incidence of concomitant labral pathology in the setting of chondral defects.32x32Neumann, G. et al. Prevalence of labral tears and cartilage loss in patients with mechanical symptoms of the hip: evaluation using MR arthrography. Osteoarthritis Cartilage. 2007; 15: 909–917

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Furthermore, labral tears treated with debridement instead of reconstruction, are associated with high rates of joint degeneration and the following need for arthroplasty.38x38Parvizi, J. et al. Arthroscopy for labral tears in patients with developmental dysplasia of the hip: a cautionary note. J Arthroplasty. 2009; 24: 110–113

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<2 cm² delamination

Chondral delamination is often encountered in hip arthroscopy and commonly associated with pincer and cam-type femoroacetabular impingement (FAI).39x39Hevesi, M. et al. Current hip cartilage regeneration/repair modalities: a scoping review of biologics and surgery. Int Orthop. 2021; 45: 319–333

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Several techniques have been described to address and repair a chondral flap, including fibrin glue,40x40Stafford, G.H., Bunn, J.R., and Villar, R.N. Arthroscopic repair of delaminated acetabular articular cartilage using fibrin adhesive. Results at one to three years. Hip Int. 2011; 21: 744–750

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suture anchor fixation41x41Sekiya, J.K., Martin, R.L., and Lesniak, B.P. Arthroscopic repair of delaminated acetabular articular cartilage in femoroacetabular impingement. Orthopedics. 2009; 32

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and scaffold implantation.42x42Tahoun, M. et al. Results of arthroscopic treatment of chondral delamination in femoroacetabular impingement with bone marrow stimulation and BST-CarGel((R)). SICOT J. 2017; 3: 51

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Case series for each treatment option demonstrated positive clinical outcomes, while no randomized trial exists to the best of our knowledge.

Studies have reported favorable outcomes for the repair of both femoral and acetabular chondral flaps with a size of <2 cm².40x40Stafford, G.H., Bunn, J.R., and Villar, R.N. Arthroscopic repair of delaminated acetabular articular cartilage using fibrin adhesive. Results at one to three years. Hip Int. 2011; 21: 744–750

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,43x43Tzaveas, A.P. and Villar, R.N. Arthroscopic repair of acetabular chondral delamination with fibrin adhesive. Hip Int. 2010; 20: 115–119

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Stafford et al followed acetabular fibrin glue repairs with a second-look arthroscopy after a mean of 28 months and reported stable results.40x40Stafford, G.H., Bunn, J.R., and Villar, R.N. Arthroscopic repair of delaminated acetabular articular cartilage using fibrin adhesive. Results at one to three years. Hip Int. 2011; 21: 744–750

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Sekiya et al used a monofilament suture anchor to reattach acetabular delamination and reported good clinical outcomes.41x41Sekiya, J.K., Martin, R.L., and Lesniak, B.P. Arthroscopic repair of delaminated acetabular articular cartilage in femoroacetabular impingement. Orthopedics. 2009; 32

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Notably, only 1 patient was treated and received concomitant treatment for FAI and labral tear, making the clinical results difficult to interpret. In the setting of type 2 Pipkin fractures, chondral delamination was addressed with bioabsorbable pin fixation, that was combined with rotational osteoplasty. At 4 years postoperatively, Harris Hip Score (HHS) was 99 and minimal arthritic changes were noted on radiographs.44x44Maluta, T. et al. Rotational osteoplasty and bioabsorbable polylactate pin fixation in pipkin type 2 fracture with acute osteochondral defect: a case report. Acta Biomed. 2016; 87: 116–121

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Small chondral lesions have also been treated with scaffold-based repairs with resulting improved subjective patient-reported outcomes, however published results for these techniques remain limited to 2 years of follow-up.45x45Rhee, C. et al. Safety profile and short-term outcomes of BST-CarGel as an adjunct to microfracture for the treatment of chondral lesions of the hip. Orthop J Sports Med. 2018; 6: 2325967118789871

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While lacking a randomized in vivo trial comparing different repair techniques of chondral delamination of the hip, Cassar-Gheiti et al conducted a cadaveric biomechanical study comparing 3 fixation techniques for chondral flap injuries.46x46Cassar-Gheiti, A.J. et al. Comparison of four chondral repair techniques in the hip joint: a biomechanical study using a physiological human cadaveric model. Osteoarthritis Cartilage. 2015; 23: 1018–1025

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Cyanoacrylate repairs, fibrin glue, and suture anchor repairs were performed and underwent mechanical loading and gait cycles. Arthroscopic controls were carried out at defined cyclical intervals. Suture anchor fixation remained stable at the endpoint of 1500 gait cycles, while fibrin glue failed at an average of 27 cycles and cyanoacrylate at an average of 635 cycles.

While long-term in vivo results are lacking, it appears reasonable to repair and fix femoral and acetabular delamination <2 cm² to maintain the native chondrocytes and cartilage superstructure. The positive results of multiple refixation techniques presented above and summarized in Table 3 suggest that the repair of even a small delamination is possible and preferred over debridement.

Table 3Hip.
StudyJournalYearLevelEnrolled participantsMean lesion size (cm²)Age (years)TreatmentOutcome parameterFollow-up timeResults
Tahoun et alJ Arthrosc Relat Surg2017IV233.540.9Acetabular Mfx and Chitosan base scaffold repairNAHS, iHOT33, HOS38.5 moSignificant improvement in all scores
Thier et alSICOT J2017III292.2130.3Acetabular MACIiHOT33, EQ-5D, NAHS19 moAll scores: Significant improvement
Oladeji et alHip Int2018IV103.824.8Femoral head osteochondral allograftHOOS17.2 moHOOS: Significant improvement in 7/10 patients
Kilicoglu et alHip Int2015IV1727Femoral head mosaicplastyHHS8 yHHS: 55-96
Khanna et alBone Joint J2014IV17>325.9Femoral head osteochondral allograftHHS41.6 moHHS: Significant improvement
Fontana et alArthrosc- J Arthrosc Relat Surg2012III30>240.7/42.3Acetabular ACI vs debridementHHS74 moHHS: Significant improvement ACI group
Girard et alHip Int2011IV104.818Femoral head mosaicplastyOHS HHS, Merle d/Aubiqne score, UCLA score, Devane score, CT29.2. moAll scores improved; 6 months CT; Intact coverage
Evans et alClin Orthop Rel Res2010IV15.532Femoral head osteochondral allograftHHS12 moHHS: 69-94
Nousiainen et alJ Orthop Trauma2010V1>518Femoral head osteochondral allograftHHS, HOOS, MFA SF-36, VAS, MRI46 moHHS: 100; HOOS: 62; MFA: 22; SF-36: 81; VAS: 0, MRI: OA changes
Maluta et alActa Biomed2016V1324Rotational osteoplasty femoral head and bio absorbable pin fixationMRI, HHS4 yHHS: 99; MRI, CT: minimal arthtritic changes
Stafford et alHip Int2011IV43not reported34.2Acetabular Mfx + Fibrin glueMHHS28 moSignificant improvement in MHHS
Tzaveas et alHip Int2010IV19not reported36Acetabular Mfx + Fibrin glueMHHS12 moSignificant improvement in MHHS
Sekiya et alOrthopedics2009V1not reported17Acetabular Mfx + Suture anchorMHHS, HOS, CADL, HOSS24 moGood results; MHHS: 96; HOSCADL: 93; HOSS: 81
Viamont-Guerra et alKnee Surg Sports Traumatol Arthrosc2019IV271.6 ± 0.728.7Femoral head mosaicplastymHHS, WOMAC12 moSignificant improvement in mHHS and WOMAC
Zelken et alJ Orthop Trauma2016V10.821Femoral head mosaicplastyHHS, Radiograph8 yHHS: 100; Radiograph: Signs of joint degeneration
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Abbreviations: ACI: autologous chondrocyte implantation; CT, computerized tomography; HHS, hip harris score; HOSCADL, hip outcome score activities of daily living; iHOT33, international hip outcome tool 33; OHS, oxford hip score; Mfx, microfracture; mHHS, modified hip Harris score; MRI, magnetic resonance imaging; VAS, isual analogue scale; WOMAC, western Ontario and McMaster universities osteoarthritis Index.

2 to 6 cm² lesions

Large femoral chondral lesions without involvement of the subchondral layer can be addressed via ACI, which has shown favorable long-term results in the knee.47x47Knutsen, G. et al. A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am. 2007; 89: 2105–2112

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,48x48Peterson, L. et al. Autologous chondrocyte transplantation. Biomechanics and long-term durability. Am J Sports Med. 2002; 30: 2–12

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However, in contrast to the knee and shoulder, the second procedure can necessitate surgical dislocation of the hip joint in order to reach and repair the cartilage defect, which can be associated with more comorbidities than an arthroscopy alone. Possible hip donor sites for use in cartilage biopsy are the non-articular femoral head-neck junction and portions of the acetabular fossa beneath the pulvinar.49x49Thier, S., Weiss, C., and Fickert, S. Arthroscopic autologous chondrocyte implantation in the hip for the treatment of full-thickness cartilage defects - a case series of 29 patients and review of the literature. SICOT J. 2017; 3: 72

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While ACI/MACI is approved by the FDA for use in the knee, there is no current formal approval for its application in the hip. Nevertheless, initial results in the use of ACI/MACI in the hip are promising. Fontana et al compared 15 patients undergoing ACI with 15 patients treated with debridement of acetabular defects of a mean size of 2.6 cm². Superior results were reported for the ACI cohort.50x50Fontana, A. et al. Arthroscopic treatment of hip chondral defects: autologous chondrocyte transplantation versus simple debridement–a pilot study. Arthroscopy. 2012; 28: 322–329

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Likewise, Thier et al found significant postoperative improvements in patient reported outcomes in 29 patients undergoing MACI with a 10 month mean follow-up.49x49Thier, S., Weiss, C., and Fickert, S. Arthroscopic autologous chondrocyte implantation in the hip for the treatment of full-thickness cartilage defects - a case series of 29 patients and review of the literature. SICOT J. 2017; 3: 72

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Krueger et al published good to excellent results for ACI in acetabular cartilage defects with an average defect size of 4.9 cm² in 32 patients. At a mean follow-up of 35.5 months, both mHHS (modified Harris Hip Score) an iHOT33 (international Hip Outcome Tool) were significantly improved.51x51Krueger, D.R. et al. Injectable autologous chondrocyte implantation (ACI) in acetabular cartilage defects-three-year results. J Hip Preserv Surg. 2018; 5: 386–392

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Akimau et al reported favorable outcomes after MACI-based treatment of FAI chondral defects up to 3.5 cm² in size at 5 years of follow-up.52x52Akimau, P. et al. Autologous chondrocyte implantation with bone grafting for osteochondral defect due to posttraumatic osteonecrosis of the hip–a case report. Acta Orthop. 2006; 77: 333–336

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Despite the small number of studies available, outcomes are generally positive. The benefits of the cell-based procedures include less donor site morbidity compared to mosaicplasty and no need for allogenic tissue transplantation such as in OCA. In pathologies that involve the subchondral layer, cell-based approaches should be used with caution as they may produce inferior results as compared to structural grafts such as OATs and OCA.53x53Kish, G., Modis, L., and Hangody, L. Osteochondral mosaicplasty for the treatment of focal chondral and osteochondral lesions of the knee and talus in the athlete. Rationale, indications, techniques, and results. Clin Sports Med. 1999; 18: 45–66 (vi)

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In the hip, OATs donor sites with good accessibility include the ipsilateral knee or non-weight bearing areas of the femoral head. Due to OATs’ ability to replace hyaline cartilage with mature structure cartilage and underlying bone rather than creating a fibrocartilage scar as with microfracture, results of OATs have been superior to microfracture in lesions sized between 2 and 6 cm².54x54Gudas, R. et al. Ten-year follow-up of a prospective, randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint of athletes. Am J Sports Med. 2012; 40: 2499–2508

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, 55x55Hangody, L. et al. Autologous osteochondral mosaicplasty. Surgical technique. J Bone Joint Surg Am. 2004; 86: 65–72

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, 56x56Solheim, E. et al. Randomized study of long-term (15-17 Years) outcome after microfracture versus mosaicplasty in knee articular cartilage defects. Am J Sports Med. 2018; 46: 826–831

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, 57x57Saris, D.B. et al. Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med. 2008; 36: 235–246

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Girard et al observed that full-thickness chondral defects with subchondral involvement and a mean defect size of 4.8 cm² demonstrated good clinical outcomes, graft integration, and a smooth chondral surface at 29 months of follow-up.58x58Girard, J. et al. Osteochondral mosaicplasty of the femoral head. Hip Int. 2011; 21: 542–548

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Similarly, Viamont-Guerra et al presented a recent series of femoral head OATs procedures with significant postoperative outcome score improvements but suggested that larger lesions (>2 cm²) did not benefit as much as smaller lesions from the procedure.59x59Viamont-Guerra, M.R. et al. Promising outcomes of hip mosaicplasty by minimally invasive anterior approach using osteochondral autografts from the ipsilateral femoral head. Knee Surg Sports Traumatol Arthrosc. 2020; 28: 767–776

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In terms of OCA, Xin et al observed significant improvements in mHHS in 22 patients treated with OCA and low conversion rates to total hip arthroplasty despite an average lesion size of 5.43 cm². Femoral cartilage lesions with a size of >8 cm² are generally considered too large for reconstruction and lead to THA in most cases (Table 2).

Table 3 summarizes studies that addressed chondral lesions of a size of 2 to 6 cm². OATs and OCA are surgical options to be considered, especially in the setting of subchondral involvement and lesions >6 cm².

Knee

Patients with articular cartilage defects of the knee can experience pain and functional impairments comparable to patients with severe OA scheduled for knee arthroplasty.60x60Heir, S. et al. Focal cartilage defects in the knee impair quality of life as much as severe osteoarthritis: a comparison of knee injury and osteoarthritis outcome score in 4 patient categories scheduled for knee surgery. Am J Sports Med. 2010; 38: 231–237

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Articular defects are identified in approximately two-thirds of all knees undergoing arthroscopy for knee pain.61x61Camp, C.L., Stuart, M.J., and Krych, A.J. Current concepts of articular cartilage restoration techniques in the knee. Sports Health. 2014; 6: 265–273

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, 62x62Aroen, A. et al. Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sports Med. 2004; 32: 211–215

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, 63x63Curl, W.W. et al. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy. 1997; 13: 456–460

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Lesions with a surface area 〈2 cm2 are considered as small in the knee and can be silent in 1 patient but lead to symptomatic pain and accelerated joint degeneration in another.61x61Camp, C.L., Stuart, M.J., and Krych, A.J. Current concepts of articular cartilage restoration techniques in the knee. Sports Health. 2014; 6: 265–273

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It remains unclear why some patients experience a significant amount of clinical symptoms, while in others, chondral injury appears silent.64x64Abraamyan, T. et al. Marrow stimulation has relatively inferior patient-reported outcomes in cartilage restoration surgery of the knee: a systematic review and meta-analysis of randomized controlled trials. Am J Sports Med. 2021; : 3635465211003595

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Small defects with limited or no clinical symptoms might make larger surgeries seem excessive and unjustified; however, a wait-and-see approach, particularly as it relates to symptomatic lesions, may have negative and devastating long-term consequences. Everhart et al calculated a substantially higher risk for total knee arthroplasty in patients with full thickness cartilage defects 〉2 cm2 compared to those with <2 cm2 lesions (HR = 5.27 [95% CI = 2.70-10.3] vs HR = 2.65 [95% CI = 1.60-4.37]).65x65Everhart, J.S. et al. Full-thickness cartilage defects are important independent predictive factors for progression to total knee arthroplasty in older adults with minimal to moderate osteoarthritis: data from the osteoarthritis initiative. J Bone Joint Surg Am. 2019; 101: 56–63

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Regardless, thorough preoperative planning is essential when treating cartilage defects to address potential concurrent pathologies, such as tibiofemoral and patellofemoral malalignment, meniscal tears, or ligamentous instability.66x66Allaire, R. et al. Biomechanical consequences of a tear of the posterior root of the medial meniscus. Similar to total meniscectomy. J Bone Joint Surg Am. 2008; 90: 1922–1931

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,67x67Krych, A.J. et al. Learning from failure in cartilage repair surgery: an analysis of the mode of failure of primary procedures in consecutive cases at a tertiary referral center. Orthop J Sports Med. 2018; 6: 2325967118773041

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Useful diagnostic studies include dedicated knee x-rays, full-length standing hip to ankle X-rays and MRI to determine the surface and depth of the defect and possible concurrent injuries of the cruciate ligaments and menisci.68x68Pestka, J.M. et al. Clinical outcome of autologous chondrocyte implantation for failed microfracture treatment of full-thickness cartilage defects of the knee joint. Am J Sports Med. 2012; 40: 325–331

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While the knee has the longest historic record for cartilage regeneration techniques, debridement/chondroplasty remains the most common cartilage procedure performed in the United States, estimated to comprise 66% of all cases.69x69DeFroda, S.F. et al. Trends in the surgical treatment of articular cartilage lesions in the United States from 2007 to 2016. J Knee Surg. 2020; 34: 1609–1616

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Debridement does not aim to restore cartilage tissue but instead is palliative and aims to remove unstable flaps and create a stable articular cartilage rim surrounding any encountered defects. We believe that debridement still poses a viable, one-stage option for the treatment of small defects (<2 cm2) in the presence of symptomatic mechanical blocks and resulting pain and disability. However, it is noteworthy that OATs produce favorable, long-term results in small cartilage defects, filling the lesion with viable, native hyaline cartilage.70x70Patil, S. and Tapasvi, S.R. Osteochondral autografts. Curr Rev Musculoskelet Med. 2015; 8: 423–428

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OATs (and pre-drilled OCAs cores) are also logistically attractive considering that like debridement, they provide a one-stage procedure without relying on fibrocartilage scar formation. Overall, OATs/OCA is preferred over microfracture and chondroplasty in young and active patients in order to maximize long-benefits. Negative aspects of the procedure, such as high costs and donor side morbidity, still have to be taken into consideration when making a treatment decision.

Given the shortcomings of microfracture, ACI and MACI were introduced to improve the treatment of large cartilage defects (>2 cm2) of the knee.71x71Minas, T. and Peterson, L. Advanced techniques in autologous chondrocyte transplantation. Clin Sports Med. 1999; 18: 13–44 (v-vi)

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,72x72Peterson, L. et al. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000; : 212–234

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Consisting of 2 separate surgical procedures, harvesting chondrocytes from a non-weight-bearing surface and implantation of the cultured cartilage cells at least 3 to 5 weeks later, the procedure is associated with good outcomes that have been reported in patients at up to 2 to 9 years of follow-up.72x72Peterson, L. et al. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000; : 212–234

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,73x73Van Assche, D. et al. Autologous chondrocyte implantation versus microfracture for knee cartilage injury: a prospective randomized trial, with 2-year follow-up. Knee Surg Sports Traumatol Arthrosc. 2010; 18: 486–495

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While second-generation ACI uses a bioabsorbable collage membrane under which the cultured cartilage cells are injected, MACI incorporates a membrane that acts as a cell carrier to distribute the cells more evenly with a density of 500,000 to 1000,000 cells per cm.2x2Ramponi, L. et al. Lesion size is a predictor of clinical outcomes after bone marrow stimulation for osteochondral lesions of the talus: a systematic review. Am J Sports Med. 2017; 45: 1698–1705

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,74x74Saris, D. et al. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: two-year follow-up of a prospective randomized trial. Am J Sports Med. 2014; 42: 1384–1394

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To date, the knee joint remains the only location where the use of ACI and MACI has been approved by both the FDA and European Medicines Agency. The relatively high costs of the treatment and its 2-stage design represent the biggest limitations to broad ACI/MACI implementation.75x75Saris, T.F.F. et al. Five-year outcome of 1-stage cell-based cartilage repair using recycled autologous chondrons and allogenic mesenchymal stromal cells: a first-in-human clinical trial. Am J Sports Med. 2021; 49: 941–947

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In intermediate and large lesions (>2 cm2), OATs and OCA comprise the most commonly used treatment options, at least in the US. Due to the limited availability of OCA, OATs and ACI are more commonly used in the EU. Levy et al reported a 82% survivorship after 10 years in 126 knees treated with OCA and a mean total graft surface area of 8.1 cm2 (range, 1-27 cm2x2Ramponi, L. et al. Lesion size is a predictor of clinical outcomes after bone marrow stimulation for osteochondral lesions of the talus: a systematic review. Am J Sports Med. 2017; 45: 1698–1705

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).76x76Levy, Y.D. et al. Do fresh osteochondral allografts successfully treat femoral condyle lesions?. Clin Orthop Relat Res. 2013; 471: 231–237

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Melugin et al recently described a hybrid technique involving (OATs) for the treatment of large lesion sizes with a mean of 2.8 cm2 and reported positive outcomes at 36 months follow-up.77x77Melugin, H.P. et al. Osteochondritis dissecans of the knee: short-term outcomes of a hybrid technique to restore a partially salvageable progeny fragment. Cartilage. 2020; 11: 300–308

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In summary, cartilage lesions of the knee (femoral condyles, trochlea, patella) typically involve a large surface area and are most commonly treated with ACI/MACI or structural grafts such as OATs and OCA. Debridement and microfracture remains in clinical use, particularly for small lesions, but evidence suggests inferior mid- and long-term results as compared to structural and biologic alternatives (Table 4).

Table 4Knee.
StudyJournalYearLevelEnrolled participantsMean lesion size (cm²)Age (years)TreatmentOutcome parameterFollow-up time (months)Results
Saris et alAm J Sports Med2009I1182.4 ± 1.2 (1-5)33.9CCI or MFKOOS36Significantly better results in CCI group, especially in patients with symptom onset <3 y
Vanlauwe et alAm J Sports Med2011I1122.4 ± 1.2 (1-5)33.4CCI or MFKOOS76Significantly better results in CCI group, especially in patients with symptom onset <3 y; no difference in lesion size subgroups
Saris et alAm J Sports Med2014I1445.5533.85MACI or MFKOOS24Cartilage defects sized ≥3 cm2 treated with MACI were statistically and clinically significantly better than MF
Knutsen et alJ Bone Joint Surg Am2016I804.832.2ACI or MFICRS, Lysholm, Short-Form-36, Tegner180Satisfactory results in 77% of patients
Volz et alInt Orthop2017I473.6 (2-10)27-47MF, AMIC glued or AMIC suturedMod. Cincinnati, ICRS, VAS, MRI60Significantly better results in both AMIC group compared to MF
Brittberg et alAm J Sports Med2018I128534MACI or MFKOOS60Cartilage defects sized ≥3 cm2 treated with MACI were statistically and clinically significant better than MF
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Abbreviations: ACI, autologous chondrocyte implantation; AMIC, autologous matrix induced chondrogenesis; CCI, characterized chondrocyte implantation; ICRS, international cartilage repair society scale; KOOS, knee injury and osteoarthtritis score; MACI, matrix induced autologous chondrocyte implantation; MF, micro fracture; VAS, visual analog scale.

Ankle

The ankle is a hinge joint with 3 articulating highly-congruent bones, namely the talus, tibia and fibula.78x78Hendren, L. and Beeson, P. A review of the differences between normal and osteoarthritis articular cartilage in human knee and ankle joints. Foot (Edinb). 2009; 19: 171–176

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Mean ankle cartilage thickness ranges from 1 to 1.7 mm whereas the knee cartilage ranges from 1.5 mm to 6 mm in thickness.79x79Millington, S.A. et al. Quantification of ankle articular cartilage topography and thickness using a high resolution stereophotography system. Osteoarthritis Cartilage,. 2007; 15: 205–211

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Small deviations in anatomy predispose the ankle to osteochondral defects and arthritis. For these reasons, it is paramount to identify and appropriately treat symptomatic cartilage lesions in the ankle.

Unlike other large, weight-bearing joints, the ankle very rarely develops OA without prior, predisposing trauma.80x80Corte-Real, N. and Caetano, J. Ankle and syndesmosis instability: consensus and controversies. EFORT Open Rev. 2021; 6: 420–431

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Once trauma occurs, ankle arthritis can become a significant source of morbidity with multiple potential treatment options.82x82Gagne, O.J. et al. Prospective cohort study on the employment status of working age patients after recovery from ankle arthritis surgery. Foot Ankle Int. 2018; 39: 657–663

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Ankle arthroplasty is a treatment option when substantial OA with multifocal chondral damage has already occurred, but the results of ankle arthroplasty are behind that seen in the knee and hip.83x83Stadler, C. et al. Intermediate to long-term clinical outcomes and survival analysis of the Salto mobile bearing total ankle prothesis. Arch Orthop Trauma Surg. 2021;

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An alternative to arthroplasty is ankle arthrodesis, however this is associated with limited range of motion, secondary mid/hindfoot arthritis, and a relatively high risk of postoperative infection and nonunion. Cartilage repair and regeneration techniques seek to prevent arthritis in an attempt to prevent or at least substantially delay the need for arthroplasty/arthrodesis. Although multiple treatment options exist, there is limited evidence supporting 1 restorative technique over another.84x84Dahmen, J. et al. No superior treatment for primary osteochondral defects of the talus. Knee Surg Sports Traumatol Arthrosc. 2018; 26: 2142–2157

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The current consensus is that debridement or bone marrow stimulation with microfracture to produce fibrocartilage is generally employed for primary smaller defects up to 1.5 cm² in size.85x85Yoshimura, I. et al. Arthroscopic bone marrow stimulation techniques for osteochondral lesions of the talus: prognostic factors for small lesions. Am J Sports Med. 2013; 41: 528–534

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, 88x88Dekker, T.J. et al. Treatment of osteochondral lesions of the talus: a critical analysis review. JBJS Rev. 2017; 5

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Several studies have investigated the treatment of talar lesions ranging from 1.0 cm to 1.7 cm² with microfracture.89x89Choi, J.I. and Lee, K.B. Comparison of clinical outcomes between arthroscopic subchondral drilling and microfracture for osteochondral lesions of the talus. Knee Surg Sports Traumatol Arthrosc. 2016; 24: 2140–2147

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Corr et al reported a 10-year follow-up of patients undergoing isolated arthroscopic microfracture for talar osteochondral defects, with a 93.3% survival and 85.7% return to sport rate at final follow-up. Shimozono et al suggested in a recent study that the use of an extracellular matrix cartilage allograft (EMCA) as an adjuvant to bone marrow stimulation (BMS) alone in small cartilage defects (1.5 cm2) provides better cartilage fill than microfracture alone on MRI.94x94Shimozono, Y. et al. Use of extracellular matrix cartilage allograft may improve infill of the defects in bone marrow stimulation for osteochondral lesions of the talus. Arthroscopy. 2021; 37: 2262–2269

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However, this did not translate to improved functional outcomes compared with microfracture alone at a mean follow-up time of 22 months. Choi et al investigated a possible threshold in lesion size that may exist for microfracture-based treatment. One hundred twenty ankles underwent arthroscopic microfracture for osteochondral lesion of the talus. Only 10 of 95 ankles (10.5%) with a defect area <1.50 cm2 demonstrated clinical failure.95x95Choi, W.J. et al. Osteochondral lesion of the talus: is there a critical defect size for poor outcome?. Am J Sports Med. 2009; 37: 1974–1980

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In contrast patients with a defect area ≥150 mm2 demonstrated a failure rate of up to 80% (20/25), highlighting the need for alternative treatment modalities for larger chondral defects.

Despite no current FDA approval, MACI is used for treatment of osteochondral lesions of the talus, particularly as it relates to larger defects. Lenz et al reported a case series of 15 patients who underwent MACI with a mean follow-up of 12.9 years. The mean size of the talar osteochondral defects was 204 mm2. Results were measured using the American Orthopaedic Foot & Ankle Society (AOFAS), Foot and Ankle Activity Measurement, and visual analog scale (VAS) scoring systems. A significant improvement in mean AOFAS score from 60 preoperatively to a mean of 84 at 12 years postoperatively was observed. The authors concluded that MACI is a reliable treatment method for talar osteochondral defects providing lasting pain relief and satisfying clinical results.96x96Lenz, C.G. et al. Matrix-induced autologous chondrocyte implantation (MACI) grafting for osteochondral lesions of the talus. Foot Ankle Int. 2020; 41: 1099–1105

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However, considering treatment costs and the need for a 2-staged procedure, the use of MACI is generally reserved for special indications in the ankle refractory to other surgical interventions.97x97Kreulen, C. et al. Seven-year follow-up of matrix-induced autologous implantation in talus articular defects. Foot Ankle Spec. 2018; 11: 133–137

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Most authors consider a lesion size of 3 cm2 as the upper limit for cartilage restoration in the ankle. DeSandis et al reported a case series of 46 patients treated for osteochondral lesions of the talus and included lesions sizes up to 5.4 cm2 but did not report results relative to lesion size, limiting the interpretation of their results as it relates to very large (>3 cm2) lesions.98x98DeSandis, B.A. et al. Arthroscopic treatment of osteochondral lesions of the talus using juvenile articular cartilage allograft and autologous bone marrow aspirate concentration. J Foot Ankle Surg. 2018; 57: 273–280

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Table 5 summarizes the evidence currently available for the treatment of chondral defects in the ankle.

Table 5Ankle.
StudyJournalYearLevelEnrolled participantsMean lesion size (cm²)Age (years)TreatmentOutcome parameterFollow-up time (months)Results
Gobbi et alArthroscopy2006II214.432Mfx, OCA, chondroplastyAOFAS, AHS, SANE, NPI, and MRI findings53No significant difference in treatments, NPI was lower in Mfx and chondroplasty groups
Domayer et alOsteoarthtritis Cartilage2012IV201.3 ± 0.430Mfx, MACTAOFAS, MRI findings, and ROI analysis65.4Similar results in both treatment groups
Tahta et alJ Orthop Surg2017IV982 ± 0.329.3Nfx; HACS with CBMAAOFAS, VAS, and MOCART41.3Better clinical and radiological results and higher cartilage quality in HACS with CBMA technique group compared to NF
Murphy et alFoot Ankle Surg2019III101majority of lesions < 1.537.1Mfx + bone marrow aspirate concentrate + fibrin glueVAS pain score, FAOS, and revision rate36Similar clinical results; Less revisions in the augmentation group
Lee et alAm J Sports Med2009IV192.2 ± 0.334.6MfxAOFAS, ICRS repair grades1290% of ankles achieved excellent results
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Abbreviations: AHS, ankle hindfoot scale; AOFAS, American orthopaedic foot and ankle society; HSS, Hannover scoring system; MOCART, magnetic resonance observation of cartilage repair tissue; MRI, magnetic resonance imaging; NPI, numeric pain intensity; RCT, randomized controlled trial; ROI, region of interest; SANE, single-assessment numeric evaluation; VAS, visual analogue scale.

Table 6

Table 6Joint overview.
Image, table 6
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Limitations

Apart from the knee joint, available data on treatment types depending on cartilage lesion size are limited. Prospective randomized controlled studies are not available for every joint and many available studies represent case studies with limited implications for treatment decisions. Furthermore, several studies included in this review do not differentiate between singular focal cartilage defects and defects that were simultaneously treated with concomitant injuries. Therefore, the reported results of cartilage repair might be confounded by concomitant ligament, fibrocartilage, or a boney