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• W2554698225 abstract "Popularity and volume of biological repair for cartilage lesions of the knee have increased substantially in the last decade. However, even with current techniques, ∼25% of patients treated with primary cartilage repair will experience failure of the procedure and likely require further surgery, either revision cartilage repair or conversion to arthroplasty. Factors such as age, activity level, malalignment, meniscal integrity, ligamentous instability and type of prior cartilage repair technique influence the indications and outcomes of revision biological repair. In this state-of-the-art review paper, the authors discuss the contributing factors for, and principles of, failed cartilage repair and its management. Popularity and volume of biological repair for cartilage lesions of the knee have increased substantially in the last decade. However, even with current techniques, ∼25% of patients treated with primary cartilage repair will experience failure of the procedure and likely require further surgery, either revision cartilage repair or conversion to arthroplasty. Factors such as age, activity level, malalignment, meniscal integrity, ligamentous instability and type of prior cartilage repair technique influence the indications and outcomes of revision biological repair. In this state-of-the-art review paper, the authors discuss the contributing factors for, and principles of, failed cartilage repair and its management. Cartilage lesions (traumatic and degenerative) are frequently observed in the knee joint. These chondral lesions do not heal and may result in development of secondary osteoarthritis.1Buckwalter JA Lane NE Athletics and osteoarthritis.Am J Sports Med. 1997; 25: 873-881Crossref PubMed Scopus (307) Google Scholar 2Shapiro F Koide S Glimcher MJ Cell origin and differentiation in the repair of full-thickness defects of articular cartilage.J Bone Joint Surg Am. 1993; 75: 532-553Crossref PubMed Scopus (1077) Google Scholar Different techniques have been used to treat these defects with various success rates. When patients experience incomplete or recurrent symptoms, or when they are unable to return to his or her desired activity level, the surgical repair attempt can be considered as failed. Unfortunately, when all techniques are considered in total, there remains a clinical failure rate up to 25% in most series. Graft dislodgement, graft resorption, technical error and overlooking a concomitant injury leading to premature graft destruction are common causes for surgical failure.3Niemeyer P Pestka JM Kreuz PC et al.Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint.Am J Sports Med. 2008; 36: 2091-209910.1177/0363546508322131Crossref PubMed Scopus (214) Google Scholar 4Khan IM Gilbert SJ Singhrao SK et al.Cartilage integration: evaluation of the reasons for failure of integration during cartilage repair: a review.Eur Cell Mater. 2008; 16: 26-39Crossref PubMed Google Scholar There has been a relative lack of attention regarding the treatment of patients with failed index cartilage repair, compared with the amount of published information on the surgical treatment of cartilage lesions in general. The clinical outcomes pertaining to this patient population are less clear, thereby rendering decision-making relying largely on expert opinions and a case-by-case evaluation of patient-specific and disease-specific characteristics.5Chahal J Thiel GV Hussey K et al.Managing the patient with failed cartilage restoration.Sports Med Arthrosc. 2013; 21: 62-6810.1097/JSA.0b013e3182900608Crossref PubMed Scopus (14) Google Scholar An overall evaluation of comorbid conditions such as malalignment, ligament instability and meniscal deficiency is mandatory to obtain a successful revision articular cartilage repair.6Minas T Gomoll AH Rosenberger R et al.Increased failure rate of autologous chondrocyte implantation after previous treatment with marrow stimulation.Am J Sports Med. 2009; 37: 902-90810.1177/0363546508330137Crossref PubMed Scopus (340) Google Scholar These comorbid conditions must be corrected. Otherwise, they can have a negative effect on the cartilage restoration procedure because of decreased contact area and abnormal increased contact pressures and shear stresses.7Harris JD Hussey K Wilson H et al.Biological knee reconstruction for combined malalignment, meniscal deficiency and articular cartilage disease.Arthroscopy. 2015; 31: 275-28210.1016/j.arthro.2014.08.012Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar As our understanding of pathophysiology and pathomechanics advance, new cartilage repair techniques are introduced and existing techniques are refined. However, no single cartilage repair technique is without any complications or failures. In this paper, we give an overview of the causes of failed cartilage repair and its management. There are a lot of studies indicating a reduction in chondrocyte function with age, such as a decline in proliferative potential, aggrecan production, collagen deposition and reaction to growth factors.8Barbero A Grogan S Schafer D et al.Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacity.Osteoarthr Cartil. 2004; 12: 476-48410.1016/j.joca.2004.02.010Abstract Full Text Full Text PDF PubMed Scopus (316) Google Scholar 9Blaney Davidson EN Scharstuhl A Vitters EL et al.Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity.Arthritis Res Ther. 2005; 7: 1338-1347Crossref PubMed Google Scholar Furthermore, while wide variations in individual health and vitality exist within each age group, age generally can be considered to be a surrogate for the presence of diffuse arthritic disease, rather than focal defects. Therefore, it is not surprising that younger patients (<30) generally have superior clinical outcome scores and more repair tissue fill on MRI with different cartilage restoration strategies.10Goyal D Keyhani S Lee EH et al.Evidence-based status of microfracture technique: a systematic review of level I and II studies.Arthroscopy. 2013; 29: 1579-158810.1016/j.arthro.2013.05.027Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar, 11Goyal D Keyhani S Lee EH et al.Evidence-based status of osteochondral cylinder transfer techniques: a systematic review of level I and II studies.Arthroscopy. 2014; 30: 497-50510.1016/j.arthro.2013.12.023Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 12Mithoefer K McAdams T Williams RJ et al.Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis.Am J Sports Med. 2009; 37: 2053-206310.1177/0363546508328414Crossref PubMed Scopus (695) Google Scholar Inferior functional outcomes have been associated with elevated body mass index (BMI, starting at a threshold of 30 kg/m2).5Chahal J Thiel GV Hussey K et al.Managing the patient with failed cartilage restoration.Sports Med Arthrosc. 2013; 21: 62-6810.1097/JSA.0b013e3182900608Crossref PubMed Scopus (14) Google Scholar A decreased cartilage volume at the repair site with microfracture has been noticed. Lower re-intervention rates for the intermediate (overweight) BMI group (16.8%) were seen with autologous chondrocyte implantation (ACI), suggesting a BMI higher than 30 (obesity; 25.0%) and a low BMI (23.7%) with a higher physical activity to be associated with worse outcomes.13Jungmann PM Salzmann GM Schmal H et al.Autologous chondrocyte implantation for treatment of cartilage defects of the knee: what predicts the need for reintervention?.Am J Sports Med. 2012; 40: 58-6710.1177/0363546511423522Crossref PubMed Scopus (84) Google Scholar The association of smoking with various health issues such as cancer, diabetes and cardiovascular disease have been well documented. Many orthopaedic conditions such as bone mineral density, fracture healing and wound repair have been documented to be adversely affected by smoking. A similar association exists between smoking and knee articular cartilage repair, with the literature suggesting an overall negative influence.14Kanneganti P Harris JD Brophy RH et al.The effect of smoking on ligament and cartilage surgery in the knee: a systematic review.Am J Sports Med. 2012; 40: 2872-287810.1177/0363546512458223Crossref PubMed Scopus (49) Google Scholar 15Jaiswal PK Macmull S Bentley G et al.Does smoking influence outcome after autologous chondrocyte implantation?: a case-controlled study.J Bone Joint Surg Br. 2009; 91: 1575-157810.1302/0301-620X.91B12.22879Crossref PubMed Scopus (52) Google Scholar Improved knee outcomes and athletic activity after microfracture were observed with higher preoperative activity levels (Tegner score >4).12Mithoefer K McAdams T Williams RJ et al.Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis.Am J Sports Med. 2009; 37: 2053-206310.1177/0363546508328414Crossref PubMed Scopus (695) Google Scholar The volume and thickness of articular cartilage increase with weight-bearing activity in athletes and adolescents.16Jones G Bennell K Cicuttini FM Effect of physical activity on cartilage development in healthy kids.Br J Sports Med. 2003; 37: 382-383Crossref PubMed Scopus (47) Google Scholar 17Jones HP Appleyard RC Mahajan S et al.Meniscal and chondral loss in the anterior cruciate ligament injured knee.Sports Med. 2003; 33: 1075-1089Crossref PubMed Scopus (56) Google Scholar A positive linear dose–response relationship exists for repeated loading activities and chondral function in the healthy athlete. However, it has been shown in a canine model that this dose–response curve reaches a threshold and that more activity can have a detrimental effect on articular cartilage.18Kiviranta I Tammi M Jurvelin J et al.Articular cartilage thickness and glycosaminoglycan distribution in the canine knee joint after strenuous running exercise.Clin Orthop Relat Res. 1992; 283: 302-308Crossref PubMed Scopus (122) Google Scholar Although different cartilage repair strategies have been successfully applied in traumatic aetiologies of cartilage disease, chronic inflammation poses specific challenges due to the altered and generally hostile joint homeostasis. An inhibition of inflammatory cytokines and introduction of cartilage-producing cells must be achieved to result in successful chondral repair. Recently, immunotherapy blocking proinflammatory cytokines has opened a new area of investigation in inflammatory arthritis, and new disease-modifying agents have significantly changed the course of the disease by stabilising symptoms and retarding or even stopping structural degeneration. However, these treatments have no effect on already damaged cartilage, and there is lack of data regarding their influence on cartilage regeneration in patients with inflammatory arthritis.19Jorgensen C Noel D Apparailly F et al.Stem cells for repair of cartilage and bone: the next challenge in osteoarthritis and rheumatoid arthritis.Ann Rheum Dis. 2001; 60: 305-309Crossref PubMed Scopus (60) Google Scholar A decrease in joint contact area and an increase in peak stresses are associated with prior subtotal meniscectomy with a 14 times increased relative risk of developing unicompartmental arthritis.20Lee SJ Aadalen KJ Malaviya P et al.Tibiofemoral contact mechanics after serial medial meniscectomies in the human cadaveric knee.Am J Sports Med. 2006; 34: 1334-134410.1177/0363546506286786Crossref PubMed Scopus (332) Google Scholar, 21McNicholas MJ Rowley DI McGurty D et al.Total meniscectomy in adolescence. A thirty-year follow-up.J Bone Joint Surg Br. 2000; 82: 217-221Crossref PubMed Scopus (177) Google Scholar, 22Roos EM Ostenberg A Roos H et al.Long-term outcome of meniscectomy: symptoms, function, and performance tests in patients with or without radiographic osteoarthritis compared to matched controls.Osteoarthr Cartil. 2001; 9: 316-32410.1053/joca.2000.0391Abstract Full Text PDF PubMed Scopus (167) Google Scholar, 23Roos H Lauren M Adalberth T et al.Knee osteoarthritis after meniscectomy: prevalence of radiographic changes after twenty-one years, compared with matched controls.Arthritis Rheum. 1998; 41: 687-69310.1002/1529-0131(199804)41:4<687::AID-ART16>3.0.CO;2-2Crossref PubMed Scopus (574) Google Scholar Meniscectomised knees develop often articular degeneration over time, due to the compromised load-bearing state. An emphasis on meniscal preservation now exists, since the knowledge on the meniscus and its function continues to grow, and an improved understanding of the biomechanical consequences of the postmeniscectomised knee. It is well documented that cartilage breakdown follows a predictable pattern after meniscal resection.24Rijk PC Tigchelaar-Gutter W Bernoski FP et al.Functional changes in articular cartilage after meniscal allograft transplantation: a quantitative histochemical evaluation in rabbits.Arthroscopy. 2006; 22: 152-15810.1016/j.arthro.2005.10.006Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar Recent research has underlined this statement, indicating that even smaller meniscal resections may result in the biomechanical equivalent of a complete meniscal removal.20Lee SJ Aadalen KJ Malaviya P et al.Tibiofemoral contact mechanics after serial medial meniscectomies in the human cadaveric knee.Am J Sports Med. 2006; 34: 1334-134410.1177/0363546506286786Crossref PubMed Scopus (332) Google Scholar Serially increasing posterior medial meniscectomies peak contact stress increased proportionally. Comparing to the intact state, medial peak contact stresses increase 43% when 50% of the medial meniscus was removed, 95% increase when 75% was removed, 123% with a segmental meniscectomy and 136% with total medial meniscectomy.20Lee SJ Aadalen KJ Malaviya P et al.Tibiofemoral contact mechanics after serial medial meniscectomies in the human cadaveric knee.Am J Sports Med. 2006; 34: 1334-134410.1177/0363546506286786Crossref PubMed Scopus (332) Google Scholar When confronted with a meniscus-deficient patient with a focal chondral defect, the surgeon must consider the benefits and risks of performing concomitant procedures. The ideal situation is to effectively address chondral and meniscal pathology concurrently, without compromising the outcome of either procedure or submitting the patient to any increased complication risk.25Rue JPH Yanke AB Busam ML et al.Prospective evaluation of concurrent meniscus transplantation and articular cartilage repair. Minimum 2-year follow-up.Am J Sports Med. 2008; 36: 1770-177810.1177/0363546508317122Crossref PubMed Scopus (127) Google Scholar Knee malalignment results in excessive loading of articular cartilage, which can cause degenerative joint disease. The mechanical axis shifts medial to the centre of the knee with varus malalignment, eventually resulting in loss of medial compartment chondral volume and thickness, as well as increased surface area of tibial and femoral denuded bone.26Sharma L Eckstein F Song J et al.Relationship of meniscal damage, meniscal extrusion, malalignment, and joint laxity to subsequent cartilage loss in osteoarthritic knees.Arthritis Rheum. 2008; 58: 1716-172610.1002/art.23462Crossref PubMed Scopus (214) Google Scholar Similarly, the mechanical axis shifts lateral to the centre of the knee with valgus malalignment, leading to increased, unbalanced lateral-sided forces. Osteotomy procedures shift load away from the damaged compartment by altering the biomechanical axis. The correction of the weight-bearing axis is the pathophysiological principle of these procedures. In this way, a rapid and irreversible progression of unicompartmental degenerative joint disease can be avoided or at least be slowed down.27Sharma L Song J Felson DT et al.The role of knee alignment in disease progression and functional decline in knee osteoarthritis.JAMA. 2001; 286: 188-195Crossref PubMed Scopus (1049) Google Scholar, 28Van Thiel G Frank RN Gupta A et al.Biomechanical evaluation of a high tibial osteotomy with a meniscal transplant.J Knee Surg. 2011; 24: 45-53Crossref PubMed Scopus (37) Google Scholar, 29Verdonk PC Demurie A Almqvist KF et al.Transplantation of viable meniscal allograft. Survivorship analysis and clinical outcome of one hundred cases.J Bone Joint Surg Am. 2005; 87: 715-72410.2106/JBJS.C.01344Crossref PubMed Scopus (245) Google Scholar Especially in young and active patients with malalignment, a concomitant osteotomy can be performed with the revision chondral repair procedure. A staged procedure can be considered with older, less active patients with lower functional demands. An osteotomy is performed first to unload the symptomatic compartment, followed by an observation period. An additional restorative cartilage procedure may not be warranted if patients react well on the osteotomy. The correction of the mechanical axis by the osteotomy should be neutral in the case of a single cartilage restoration, however, slightly beyond neutral in the setting of pain and osteoarthritis.5Chahal J Thiel GV Hussey K et al.Managing the patient with failed cartilage restoration.Sports Med Arthrosc. 2013; 21: 62-6810.1097/JSA.0b013e3182900608Crossref PubMed Scopus (14) Google Scholar Some cartilage lesions may become more rapidly symptomatic than others in the presence of ligamentous instability. A concomitant anterior cruciate ligament (ACL) reconstruction and chondral restoration procedure can be performed in the case of failed cartilage repair associated with instability due to an ACL deficiency, with an overall goal of restoring joint kinematics. Bony tunnel expansion is frequently seen with previously failed ACL repair and can be managed with a staged bone-grafting procedure. After successful grafting, an ACL repair can subsequently be combined with the appropriate cartilage restorative procedure. Revision ACL reconstruction in this setting most commonly uses allografts.30Alford JW Cole BJ Cartilage restoration, part 1: basic science, historical perspective, patient evaluation, and treatment options.Am J Sports Med. 2005; 33: 295-306Crossref PubMed Scopus (312) Google Scholar Patellofemoral chondral lesions are very challenging because of the high axial and shear forces in this part of the knee joint. This type of defects is often associated with abnormal pressure, such as an excessive lateral position of the patella on the trochlea or a lateral compression syndrome, which can lead to eccentric cartilage damage. Therefore, patellofemoral lesions are often treated with a concomitant osteotomy of the tibial tubercle to normalise patellofemoral contact pressures. The degree of anteriorisation versus medialisation can be decided on the basis of the maltracking (tibial tuberosity – trochlear groove distance), the patient's history of instability or osteoarthritis.31Beck PR Thomas AL Farr J et al.Trochlear contact pressures after anteromedialization of the tibial tubercle.Am J Sports Med. 2005; 33: 1710-171510.1177/0363546505278300Crossref PubMed Scopus (102) Google Scholar, 32Farr J Schepsis A Cole B et al.Anteromedialization: review and technique.J Knee Surg. 2007; 20: 120-128Crossref PubMed Scopus (38) Google Scholar, 33Rue JP Colton A Zare SM et al.Trochlear contact pressures after straight anteriorization of the tibial tuberosity.Am J Sports Med. 2008; 36: 1953-195910.1177/0363546508317125Crossref PubMed Scopus (51) Google Scholar Young patients with early degeneration are a challenging population due to a combination of high functional activities and limited treatment options. Short-term pain relief can be achieved with conservative measures such as injection and physical therapy but are only palliative in nature. Therefore, chondral repair—while normally not indicated for the treatment of osteoarthritis—has become a focus of increased interest due to its capacity to lead to symptom relief and to change the progression of degenerative disease, with the hope of delaying or avoiding the need for arthroplasty. However, to provide a normalised biomechanical environment, concomitant procedures such as meniscal transplantation and osteotomy remain of crucial importance.34Gomoll AH Filardo G Almqvist FK et al.Surgical treatment for early osteoarthritis. Part II: allografts and concurrent procedures.Knee Surg Sports Traumatol Arthrosc. 2012; 20: 468-48610.1007/s00167-011-1714-7Crossref PubMed Scopus (81) Google Scholar Marrow stimulating techniques (MSTs) have been regarded as ‘non-bridge-burning’ techniques due to the belief that they would not adversely affect subsequent chondral repair procedures such as ACI. However, subchondral bone changes have been observed in up to one-third of patients treated with microfracture such as formation of subchondral cysts, thickening of the subchondral bone and intralesional osteophytes.35Dhollander A Moens K van der Maas J et al.Treatment of patellofemoral cartilage defects in the knee by autologous matrix-induced chondrogenesis (AMIC).Acta Orthop Belg. 2014; 80: 251-259PubMed Google Scholar 36Dhollander AA Verdonk PC Lambrecht S et al.The combination of microfracture and a cell-free polymer-based implant immersed with autologous serum for cartilage defect coverage.Knee Surg Sports Traumatol Arthrosc. 2012; 20: 1773-178010.1007/s00167-011-1763-yCrossref PubMed Scopus (37) Google Scholar Similar findings are also seen in chronic defects. Chronic defects are associated with lower outcomes after any type of cartilage repair, including ACI. This all has led to concerns that treatment with MST could adversely affect subsequent cartilage repair procedures.37Gomoll AH Madry H Knutsen G et al.The subchondral bone in articular cartilage repair: current problems in the surgical management.Knee Surg Sports Traumatol Arthrosc. 2010; 18: 434-44710.1007/s00167-010-1072-xCrossref PubMed Scopus (272) Google Scholar Interestingly, subchondral changes also occur following ACI. Bone marrow oedema can be observed in up to 78.9% of the cases treated with third-generation ACI. However, its presence is not correlated with worse clinical outcomes.36Dhollander AA Verdonk PC Lambrecht S et al.The combination of microfracture and a cell-free polymer-based implant immersed with autologous serum for cartilage defect coverage.Knee Surg Sports Traumatol Arthrosc. 2012; 20: 1773-178010.1007/s00167-011-1763-yCrossref PubMed Scopus (37) Google Scholar Defects <2 cm2 that are adequately contained (or shouldered) can be asymptomatic and only slowly progress, thus potentially having the most favourable prognosis. Contained lesions are lesions whereby the cartilage rim protects the defect base from load during weightbearing. The role of cartilage lesion size and surrounding rim cartilage thickness in the force transmission at the base of the defect during weightbearing remains yet to be determined. It is known that a biomechanically unfavourable environment for cartilage repair exists with chondral defects 2 cm2 or greater in size, with an observed loss of containment and an inability of the rim cartilage to effectively shoulder weight-bearing loads.38Niehammer TR Valentin S Gulecyuz MF et al.Bone marrow edema in the knee and its influence on clinical outcome after matrix-based autologous chondrocyte implantation: results after 3-year follow-up.Am J Sports Med. 2015; 43: 1172-117910.1177/0363546515573935Crossref PubMed Scopus (33) Google Scholar Subchondral bone changes are frequently associated with failed chondral repair, both as a result of, as well as a potential cause. In contrast to the extensive promising outcomes published in the past decades concerning treatment of focal chondral defects, the problem of osteochondral defects penetrating into the underlying subchondral bone has not received much attention so far. A fully understanding of the subchondral bone physiology is mandatory to adequately assess and treat osteochondral lesions. The subchondral bone plate fulfils mechanical and metabolic functions to current knowledge and is an active site of remodelling. Any cartilage repair attempt is likely to fail without support from an intact subchondral bed. This field of osteoarticular repair continues to evolve.37Gomoll AH Madry H Knutsen G et al.The subchondral bone in articular cartilage repair: current problems in the surgical management.Knee Surg Sports Traumatol Arthrosc. 2010; 18: 434-44710.1007/s00167-010-1072-xCrossref PubMed Scopus (272) Google Scholar One of the future directions of chondral repair lies in optimising diagnostics to recognise subchondral bone changes that might affect focal cartilage repair, as well as advanced treatment options that allow us to restore the entire osteochondral unit.37Gomoll AH Madry H Knutsen G et al.The subchondral bone in articular cartilage repair: current problems in the surgical management.Knee Surg Sports Traumatol Arthrosc. 2010; 18: 434-44710.1007/s00167-010-1072-xCrossref PubMed Scopus (272) Google Scholar The cartilage defect size is an important factor in determining the outcome of any intervention, as smaller defects preserve ‘containment’, whereby the rim cartilage protects the base of the defect from load during weightbearing. Cartilage defect size also influences fibrocartilage remodelling after repair. A biomechanical threshold of 2 cm2 (16-mm diameter) has been identified, whereby lesions ≥2 cm2 in size experienced significantly larger load increases at the defect base when comparing the loaded and unloaded states.39Triche R Mandelbaum BR Overview of cartilage biology and new trends in cartilage stimulation.Foot Ankle Clin. 2013; 18: 1-1210.1016/j.fcl.2012.12.001Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar This finding correlates with clinical studies that link smaller defect size with improved repair cartilage fill rates as seen on MRI and increased return rates to high-impact sports after repair.40Lacy KW Cracchiolo A Yu S et al.Medial femoral condyle cartilage defect biomechanics: effect of obesity, defect size, and cartilage thickness.Am J Sports Med. 2016; 44: 409-41610.1177/0363546515613517Crossref PubMed Scopus (20) Google Scholar Different studies have demonstrated promising outcomes of treatment of cartilage lesions located on the medial and lateral femoral condyles, in contrast to those located in the patellofemoral joint. These lesions are still a challenge and associated with inferior outcomes. Various cartilage repair techniques have shown an inferior proportion of satisfactory clinical results following treatment of patellofemoral defects. Moreover, larger chondral patellar lesions associated with minor outcomes. Chondral defects located on the lateral patellar facet are associated with superior clinical results than those located on the medial facet or those involving both facets. The specific biomechanical properties of the patellofemoral compartment of the knee joint are a possible explanation for the inferior results. The shearing forces are higher in the patellofemoral joint than in the medial and lateral compartments. These higher shearing forces are less beneficial to the differentiation of cartilage cells than the hydrostatic forces which are dominant in the femoral condyle regions. Moreover, during stair climbing, for example, the forces located in the patellofemoral compartment can reach out to more than seven times body weight.41Niemeyer P Steinwachs M Erggelet C et al.Autologous chondrocyte implantation for the treatment of retropatellar cartilage defects: clinical results referred to defect localisation.Arch Orthop Trauma Surg. 2008; 128: 1223-123110.1007/s00402-007-0413-9Crossref PubMed Scopus (88) Google Scholar Single defects are more likely to be caused by a trauma, whereas multiple defects are more associated with degenerative joint disease and/or repetitive microtrauma. As a consequence, the outcomes of patients with multiple cartilage defects are worse than patients with a single defect.42Solheim E Øyen J Hegna J et al.Microfracture treatment of single or multiple articular cartilage defects of the knee: a 5-year median follow-up of 110 patients.Knee Surg Sports Traumatol Arthrosc. 2010; 18: 504-50810.1007/s00167-009-0974-yCrossref PubMed Scopus (46) Google Scholar There can be a large delay between onset of symptoms and eventual treatment of a cartilage defect, frequently because of a referral system via a general practitioner or another orthopaedic surgeon. The time from onset of symptoms can affect the treatment response. It has been shown that cartilage repair performs better in more acute lesions than chronic lesions.43Vanlauwe J Saris DB Victor J et al.Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: early treatment matters.Am J Sports Med. 2011; 39: 2566-257410.1177/0363546511422220Crossref PubMed Scopus (248) Google Scholar A published review on learning of osteoarthritis (OA) by studying the healthy people pointed to the fact that knee structural changes may be reversible.44Ratzlaff CR Liang MH New developments in osteoarthritis: prevention of injury-related knee osteoarthritis–opportunities for the primary and secondary prevention of knee osteoarthritis.Arthritis Res Ther. 2010; 12: 21510.1186/ar3113Crossref PubMed Scopus (26) Google Scholar Overall, these findings do suggest that early intervention could potentially prevent or even reverse some structural changes that may evolve into knee OA as tissue regeneration appears to be better in fresh defects45Ding C Jones G Wluka AE et al.What can we learn about osteoarthritis by studying a healthy person against a person with early onset of disease?.Curr Opin Rheumatol. 2010; 22: 520-52710.1097/BOR.0b013e32833b90e9Crossref PubMed Scopus (45) Google Scholar (boxes 1 and 2). 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• W2554698225 title "Treatment of failed cartilage repair: State of the Art" @default.
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