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(iv) Treatment options for articular cartilage damage in the knee
MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS
(ii) Treatment options for articular cartilage damage in the knee
Basic science Articular cartilage is a thin layer of highly specialised connective tissue with complex viscoelastic biomechanical properties. It provides a smooth, lubricated surface for articulation and facilitates the transmission of loads to the underlying subchondral bone. Articular cartilage is historically described as avascular, alymphatic and aneural, and as such has a limited capacity for intrinsic healing and repair. Hyaline articular cartilage is 2e4 mm thick and is composed of a dense extracellular matrix (ECM) composed of water, collagen (predominantly type 2), proteoglycans, non-collagenous proteins and glycoproteins. The cellular component consists of specialised chondrocytes. Three zones of articular cartilage are recognised: superficial (10%e20% of volume), middle (40%e60%), deep (30%) and the calcified zone (Figure 1). The superficial zone protects the deeper layers from shear stresses and the collagen fibres are aligned parallel to the surface to facilitate this. The middle zone has obliquely oriented collagen and resists compressive forces. The deep zone provides the greatest resistance to compressive stresses and the collagen fibres here are arranged perpendicular to the articular surface. This zone has the highest proteoglycan content and the lowest water content. The calcified layer anchors the collagen fibrils of the deep zone to the subchondral bone. Chondrocytes are metabolically active and are derived from mesenchymal stem cells that play a role in the development, maintenance and repair of the ECM. A deep laceration to articular cartilage (through the tidemark between the deep and calcified zones) leads to fibrocartilaginous healing from undifferentiated mesenchymal cells. This response is initiated by bleeding, haematoma and stem cell migration. The resultant cartilage is largely type 1 collagen, which has inferior biomechanical properties to resist wear. A superficial laceration leads to some degree of chondrocyte proliferation but limited healing. Chondral injury, usually from trauma or degeneration, can result in mechanical knee symptoms, pain and functional impairment and ultimately premature secondary osteoarthritis.
James Donaldson Francois Tudor Ian D McDermott
Abstract Chondral damage within the knee of young patients remains a challenge to orthopaedic surgeons, with the chance of resulting mechanical symptoms limiting activity and the risk of progression to osteoarthritis. There are a number of different treatment options which utilize one of two principles for filling chondral defects: either bone marrow stimulation leading to fibrocartilaginous repair or transplantation of mature hyaline cartilage into the defect. In this article we review the current treatment options for symptomatic chondral damage within the knee, discussing the basic science, techniques involved and the evidence supporting each method.
Keywords cartilage transplant; chondral damage; chondroplasty; microfracture
Introduction Articular cartilage damage is commonly seen in the elderly as part of the pathological process of arthritis, and can relatively easily be managed with arthroplasty when symptoms are sufficiently severe. Articular cartilage damage in the younger population is a far more challenging dilemma. Arthroplasty in active, younger patients often gives inferior outcomes and results in premature implant failure rates due to the higher functional demands being placed on the implant. It is therefore vital for orthopaedic surgeons to be aware of the different options available for the treatment of cartilage injuries in order to delay the onset of symptomatic arthritis and the need for joint replacement surgery.
Microfracture Microfracture is a well-established procedure and one of the most widely used treatment techniques for chondral lesions of the knee. It was developed by Steadman1 and is a form of bone marrow stimulation. It is performed arthroscopically and is a relatively simple procedure. It also has low costs compared to other treatment modalities. The primary indication is for full thickness articular cartilage defects on the femoral condyles without significant bone loss (Outerbridge grade 3e4) measuring less than 2e4 cm. The procedure involves debridement of all unstable articular cartilage around the defect down to subchondral bone. Crucial to the repair process is creating a contained lesion with vertical edges of stable cartilage surrounding it. Multiple perforations of the subchondral plate are performed in order to promote bleeding and create a stable blood clot containing mesenchymal stem cells within the lesion. Holes are made perpendicular to the defect a few mm apart, starting peripherally (Figure 2a). A sufficient depth must be drilled or perforated to reach the bone marrow (Figure 2b). This is confirmed when the tourniquet is
James Donaldson MBBS BSc FRCS (Tr & Orth) Fellow, Lower Limb Reconstruction & Arthroplasty, Holland Orthopaedic & Arthritic Centre, Sunnybrook Health Sciences, Toronto, Canada. Conflict of interest: none declared. Francois Tudor MBBS MSc FRCS (Tr & Orth) Fellow, Lower Limb Reconstruction & Arthroplasty, Holland Orthopaedic & Arthritic Centre, Sunnybrook Health Sciences, Toronto, Canada. Conflict of interest: none declared. Ian D McDermott MBBS MS FRCS (Orth) FFSEM (UK) Consultant Orthopaedic Surgeon, London Sports Orthopaedics, Honorary Professor Associate, Brunel University, London Sports Orthopaedics, London, UK. Conflict of interest: none declared.
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Please cite this article in press as: Donaldson J, et al., (ii) Treatment options for articular cartilage damage in the knee, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.11.009
MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS
smaller lesions (<4 cm2).8 Long-term quality data is lacking,9 but even with meticulous patient selection and technique, studies suggest the initial clinical effectiveness is reduced after 24 months.6,10,11 The most common problem that can lead to poorer outcomes is bony overgrowth and its incidence has been reported as between 25 and 49% in different studies.5,12 Numerous adjuncts to microfracture have also been described to improve the stability of the initial clot and the subsequent infilling of the chondral lesion. Biomembranes or scaffold devices,13,14 thrombogenic and adhesive polymers,15 growth factors,16,17 hyaluronic acid viscosupplementation,18 stem cells19 and platelet rich plasma20 have all shown some benefit in animal or lab studies but remain to be proven in the human population.
Abrasion arthroplasty Figure 1 Articular cartilage structure.
Arthroscopic abrasion arthroplasty was introduced over 30 years ago as an alternative to existing open procedures. It involves debridement of the inflamed and degenerate tissues, as well as abrasion of the sclerotic exposed bone to expose viable bone and surface vascularity. In the earlier version of this technique, multiple superficial dimples were created in the sclerotic subchondral bone to produce areas of fibrocartilaginous repair. The technique was subsequently extended to removing the entire superficial layer of the subchondral bone plate, resulting in fibrocartilage repair over the entire lesion.21 This repair has some of the properties of articular cartilage (similar to microfracture) but again differs biomechanically. Post-operatively patients need to remain non-weightbearing for 2 months to protect the blood clot from dislodging during the tissue maturation phase. Historically this procedure was used for older patients with degenerative joint disease who did not want a joint replacement. It may also be combined with a realignment procedure if indicated. Results have been variable and often are not comparable between groups due to differing indications, patient heterogeneity, case selection, surgical technique, depth of abrasion and post-operative regimens.22e24
deflated at the end of the procedure and fatty droplets are noted to be coming from the channels. Typical microfracture holes on the medial femoral condyle Penetration of subchondral bone with the microfracture awl The mesenchymal stem cells are able to differentiate into fibrochondrocytes, which contribute to fibrocartilaginous repair over the first few weeks. This fibrocartilage contains more variable types of collagen and has inferior biomechanical properties to native hyaline cartilage. The post-operative regime is demanding for the patient, but thought to be vital for success. Non-weight bearing and continuous passive motion at 0e60 degrees only is permitted in the first 6 weeks. This is thought to improve cartilage nutrition and stimulate mesenchymal stem cell differentiation.2,3 Full return to activities is usually permitted at 3 months. Published results are variable. Steadman et al. reported the follow-up of 71 patients for an average of 11 years.4 All patients were under 45 years of age, had full thickness defects and no other intra-articular pathology. At the final follow-up, significant functional improvements were noted using multiple outcome measures. Similarly, Mithoefer et al.5 found a good to excellent results in 67% of patients at a mean of 3.6 years after the operation. Better outcomes have been observed in younger patients,6 in particular those under 40 years of age7 and in those with
Autologous chondrocyte implantation (ACI) ACI is a two-stage tissue engineering procedure that was originally performed by Brittberg and Peterson25 in 1987. The first stage consists of an arthroscopic biopsy of hyaline articular cartilage from a non-weightbearing portion of the knee.
Figure 2 Diagramtatic representation of microfracture of the medial femoral condyle (2a) and magnified view showing subchondral bone penetration (2b).
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MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS
Unlike microfracture and other marrow stimulation techniques, the goal is to achieve hyaline cartilage coverage. Roberts et al.27 demonstrated 22% hyaline cartilage cover, 48% mixed hyaline and fibrocartilage and 30% fibrocartilage. Peterson et al.28 evaluated 62 femoral condyle grafts and showed that 73% had a hyaline-like appearance at arthroscopy and 67% had histological hyaline characteristics. Zaslav et al.29 prospectively assessed the effectiveness of ACI in 126 patients with previously failed interventions for articular cartilage defects of the knee. 76% were deemed to have a good clinical result at a mean follow-up of four years. The results did not differ if the patient had previously had debridement or a marrow stimulation procedure. Poorer outcomes are associated with a raised BMI, smoking, age over 50 years, worker’s compensation and prolonged duration of symptoms.30e32
Chondrocytes are extracted from the biopsy and expanded in culture. These chondrocytes are then re-implanted into the chondral defect during a second-stage open procedure following debridement of the damaged articular surface. As with microfracture, a stable cartilage rim is required to house the transplanted cells. ACI techniques have evolved over time. First generation ACI involved the use of a periosteal flap (ACI-P) or a Type I/III collagen sheet (ACI-C) sutured to the surrounding cartilage to create a contained reservoir for the chondrocyte cell suspension (Figure 3). Second generation techniques used bio-absorbable scaffolds or matrices containing the autologous cells that were then held in place by fibrin glue (e.g. matrix associated ACI or MACI). The more recent third generation techniques use a tissue engineered three-dimensional cartilage cell graft aiming to give a more uniform seeding of the cultured chondrocytes. Post-operatively, the patient is managed fully weight bearing in a knee brace fixed in extension for one week. Progressive flexion and extension exercises are then introduced to provide a chondrogenic stimulus, with the aim of achieving a full range of movement by 6 weeks. Indications are similar to microfracture: full thickness articular cartilage defects in patients less than fifty years old in the absence of malalignment, instability, osteoarthritis or rheumatoid arthritis. In some centres the procedure has been combined with re-alignment surgery and/or ACL reconstruction in either one or two stages and/or meniscal allograft transplantation. Initial outcomes were reported by Brittberg et al. in 1994.25 Satisfactory to good clinical outcomes were published in patients with a mean follow-up of 39 months. Biopsies showed that eleven of fifteen femoral and one of the seven patella transplants had the appearance of hyaline cartilage. Peterson et al.26 reported the two-to nine-year functional and histological data of 101 patients treated with ACI, demonstrating good to excellent results in isolated femoral lesions (67%), osteochondritis dissecans (89%), the patella (65%) and femoral condyle with ACL reconstruction (75%). Histological analysis of 37 specimens showed the formation of hyaline-like tissue in those achieving good to excellent results.
Radiofrequency chondroplasty In recent years radiofrequency (RF) energy has become a popular tool during knee arthroscopy to debride and contour rough and irregular edged articular cartilage defects. A RF probe produces a plasma field as a result of electrolyte oscillation and a localised heating effect through molecular friction.33 Between 40 and 70 C the collagen in the articular cartilage becomes denatured. As it cools, new bonds are formed creating fibres arranged more parallel to the joint surface.34 It is thought these fibres may be more resistant to shear stress and subsequent degradation compared to a surface left by mechanical debridement alone. Despite the biological arguments, clinical results and data are relatively lacking. There are also potential side effects of RF energy including chondrocyte death and osteonecrosis from excessive heat production. Most recently two studies (one a randomised prospective RCT, the other a prospective review of RF chondroplasty) showed no evidence of any increased risk of osteonecrosis compared with mechanical debridement alone.35,36 In the United Kingdom the National Institute for Health and Care Excellence (NICE) has suggested RF chondroplasty is beneficial, at least in the short-term, for symptomatic discrete, chondral defects, with no major safety concerns. In addition Spahn et al.37 reported improvements at 4 years post-operatively in knee scores, need for further surgery and progression of disease in the RF group compared to the mechanical debridement group.
Autologous matrix-induced chondrogenesis (AMIC) AMIC combines the microfracture and bone marrow stimulation method described by Steadman with a collagen I/III matrix (Chondro-Glide, Geistlich Pharma AG, Wolhusen, Switzerland) that serves to act as a scaffold for new cells. It was first described by Behrens et al. in 2003.38 The blood clot formed in microfracture is fragile and has little ability to withstand tangential forces. An implanted collagen matrix scaffold over the prepared cartilage defect is used in AMIC to improve the mechanical stability and provide a better platform for cartilage repair. Only one stage is needed, there is no donor site morbidity and it is more cost effective than ACI.39
Figure 3 Intra-operative photograph of cell injection during ACI-C. Reproduced with permission. Treating articular cartilage injuries of the knee in young people. BMJ 2010; 340: 998. Macmull S, Skinner J, Bentley G, Carrington R, Briggs T.
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MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS
scaffold for stem cell differentiation. Data and long-term outcomes are minimal.43,44
The procedure can be done open or arthroscopically. The chondral defect is prepared in much the same way as for microfracture. The collagen membrane is then appropriately sized and circles of it are placed in the cartilage defect (Figure 4a). Fibrin glue is applied to all membrane covered areas (Figure 4b and c) and the knee is flexed and extended to check the membrane stability. Published outcomes are limited. In a follow-up of 27 patients an improvement in all clinical scores was seen in 87% of patients40 and follow-up MRI analysis showed moderate to complete in-filling. A recent prospective study of 17 patients showed that 13 of the patients were satisfied or extremely satisfied.41 Gille et al.42 assessed 57 patients with a mean defect size of 3.4 cm at two years follow-up. They found significant improvements in the Lysholm score at 1 year and further improvements at 2 years.
Autologous osteochondral transplantation (osteoarticular transfer system [OATS] or mosaicplasty) This technique involves transplanting multiple small cylindrical autogenous osteochondral plugs from a non-weightbearing, peripheral part of the knee to the articular cartilage defect (Figure 5). The procedure is done in a single stage, either open or arthroscopically. There are commercial kits available which aim to transplant a plug 1 mm bigger than the recipient hole to achieve a press fit. The procedure is limited by the availability of graft that can be harvested, potential differences in structure, thickness and contours between donor and recipient cartilage, as well as graft subsidence. In addition, absence of fill and the potential dead space between plugs may limit the quality of the repair. Clinical use began in 1992.45 Indications include full thickness defects less than 4 cm.2 The largest series of 831 mosaicplasties was published by Hangody and Fules.46 They reported good to excellent results for 92% of femoral lesions, 87% of tibial lesions and 79% of patellofemoral lesions. 80% of the second look arthroscopies demonstrated congruent gliding surfaces and histological
Chondrotissue Chondrotissue is similar to AMIC. It involves a one-step procedure whereby a cell free scaffold of polyglycolic and hyaluronic acid is inserted after bone marrow stimulation. It theoretically offers protection of the bleeding bone and prevents dispersion of the mesenchymal stem cells into the joint, as well as providing a
Figure 4 AMIC. (a) The membrane matching the cartilage defect. (b) and (c) The membranes covered with tissue glue. Reproduced with permission from Surg Sports Traumatol Arthrosc 2012; 20: 922e925. Tomasz Piontek, Kinga Ciemniewska-Gorzela, Andrzej Szulc, Jakub Naczk, Micha1 S1omczykowski. Allarthroscopic AMIC procedure for repair of cartilage defects of the knee.
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Conclusion The treatment of articular cartilage lesions remains a challenge and remains controversial. There are a number of treatment options for symptomatic chondral defects in the knee. Procedures either involve some form of bone marrow stimulation in an effort to recruit mesenchymal stem cells and a fibrocartilaginous repair, or cartilage transplant with the hope of forming new hyaline cartilage. Outcomes for each technique vary and quality data is lacking. Knutsen et al.57 found no difference between ACI and microfracture; Bentley et al.58 found better results for ACI than OATS; Horas et al.59 reported better clinical histological and clinical results with OATS compared to ACI. The only study by a single surgeon comparing microfracture, ACI and OATS was performed and published by Lim et al.60 Post-operative functional examination, follow-up MRI appearances and arthroscopic evaluation, were all used to compare the treated patients. Seventy knees were assessed in patients with isolated cartilage defects and otherwise normal knees. All three procedures showed improvements in functional outcome scores but there was no observable difference in clinical scores, range of movement, follow-up MRI or arthroscopic appearance between the groups. A systematic review in 2011 compared studies on the current treatment of chondral defects of the knee.61 The authors noted there was little level one or two evidence and that studies were often difficult to compare due to heterogeneity and unvalidated scores. They concluded no evidence-based results could be defined between the treatment groups for articular cartilage repair. Each technique has its own advantages and disadvantages and the choice ultimately depends on the surgeon’s preference and familiarity. It is also important to assess and treat any other co-existing pathology such as malalignment, patellar maltracking or bone defects. A
Figure 5 Autologous osteochondral transplantation.
evidence of hyaline cartilage. Similarly, Ozturk et al.47 showed 85% good to excellent results and excellent fill in 84% on MRI.
Osteochondral allografts The use of massive osteochondral allografts remains a salvage procedure following failed previous therapies for large chondral or osteochondral lesions, or where there is extensive bone loss and it is felt that a total knee replacement is not appropriate. A cadaver graft consisting of intact viable articular cartilage and its underlying subchondral bone are transplanted into the defect. It is an expensive procedure and is technically demanding. Graft availability may also be limited, particularly in the UK. There is a risk of disease transmission, immunological rejection and possible incomplete graft incorporation. Grafts can be fresh, cryopreserved or fresh-frozen. Fresh allograft is histologically and functionally preferred48 and should be implanted within 24 days.49 Fixation can be achieved with internal fixation for larger asymmetric grafts or for regular contained defects the press fit plug technique can be used. A number of studies have confirmed the long-term survival of donor chondrocytes after transplantation,50,51 likely due to the relative immunoprivilege of the avascular hyaline cartilage. Williams et al.52 showed in retrieval specimens at an average survival of 42 months that the allograft bone was necrotic but being replaced by creeping substitution, which provided a stable platform for the transplanted articular surface. Gross et al.53 reported 95% survival at five years, 85% survival at ten years and 74% at fifteen years for post-traumatic disease in the femoral condyles. Inferior results were seen with tibial allografts. The authors suggested that a high density of viable chondrocytes and mechanical stability of the allograft are crucial for long-term survival. Similarly, Levy et al.54 demonstrated improvements in pain and function of 129 transplants of the medial femoral condyle as well as 82% survival at ten years. Outcomes from other studies show inferior results in primary osteoarthritis, inflammatory arthropathy, limb malalignment, workers’ compensation and bipolar knee lesions.55,56
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53 Gross AE, Kim W, Las Heras F, Backstein D, Safir O, Pritzker KPH. Fresh osteochondral allografts for posttraumatic knee defects: long-term follow-up. Clin Orthop Relat Res 2008; 466: 1863e70. 54 Levy YD, Gortz S, Pulido PA, McCauley JC, Bugbee WD. Do fresh osteochondral allografts successfully treat femoral condyle lesions? Clin Orthop Relat Res 2013; 471: 231e7. 55 Bugbee WD, Convery FR. Osteochondral allograft transplantation. Clin Sports Med 1999; 18: 67e75. 56 Davidson PA, Rivenburgh DW, Dawson PE, Rozin R. Clinical, histologic, and radiographic outcomes of distal femoral resurfacing with hypothermically stored osteoarticular allografts. Am J Sports Med 2007; 35: 1082e90. 57 Knutsen G, Engebretsen L, Ludvigsen TC, et al. Autologous chondrocyte implantation compared with microfracture in the knee: a randomized trial. J Bone Joint Surg Am 2004; 86: 455e64. 58 Bentley G, Biant LC, Carrington RW, et al. A prospective, randomized comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Joint Surg Br 2003; 85: 223e30. 59 Horas U, Pelinkovic D, Herr G, Aigner T, Schnettler R. Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint: a prospective, comparative trial. J Bone Joint Surg Am 2003; 85: 185e92. 60 Lim Hong-Chul, Bae Ji-Hoon, Song Sang-Heon, Park Young-Eun, Kim Seung-Ju. Current treatments of isolated articular cartilage lesions of the knee achieve similar outcomes. Clin Orthop Relat Res 2012; 470: 2261e7. 61 Benthien J, Schwaninger M, Behrens P. We do not have evidence based methods for the treatment of cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc 2011; 19: 543e52.
43 Erggelet C, Endres M, Neumann K, et al. Formation of cartilage repair tissue in articular cartilage defects pretreated with microfracture and covered with cell-free polymer-based implants. J Orthop Res 2009 Oct; 27: 1353e60. 44 Siclari A, Mascaro G, Gentili C, Kaps C, Cancedda R, Boux E. Cartilage repair in the knee with subchondral drilling augmented with a platelet-rich plasma-immersed polymer-based implant. Knee Surg Sports Traumatol Arthrosc 2014 Jun; 22: 1225e34. 45 McCoy B, Miniaci A. Osteochondral autograft transplantation/mosaicplasty. J Knee Surg 2012; 25: 99e108. 46 Hangody L, Fules P. Autologous osteochondral mosaicplasty for the treatment of full-thickness defects of weight-bearing joints: ten years of experimental and clinical experience. J Bone Joint Surg Am 2003; 2(suppl 85): 25e32. 47 Ozturk A, Ozdemir MR, Ozkan Y. Osteochondral autografting (mosaicplasty) in grade IV cartilage defects in the knee joint: 2- to 7year results. Int Orthop 2006; 30: 200e4. €rtz S, Chen AC, et al. Treatment of articular cartilage 48 Pallante AL, Go defects in the goat with frozen vs fresh osteochondral allografts: effects on cartilage stiffness, zonal composition, and structure at six months. J Bone Joint Surg Am 2012; 94: 1984e95. 49 Pearsall IAW, Tucker JA, Hester RB, Heitman RJ. Chondrocyte viability in refrigerated osteochondral allografts used for transplantation within the knee. Am J Sports Med 2004; 32: 125e31. 50 Langer F, Gross AE. Immunogenicity of allograft articular cartilage. J Bone Joint Surg Am 1974; 56: 297e304. 51 McGoveran BM, Pritzker KP, Shasha N, Price J, Gross AE. Long-term chondrocyte viability in a fresh osteochondral allograft. J Knee Surg 2002; 15: 97e100. 52 Williams SK, Amiel D, Ball ST, et al. Analysis of cartilage tissue on a cellular level in fresh osteochondral allograft retrievals. Am J Sports Med 2007; 35: 2022e32.
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(ii) Treatment options for articular cartilage damage in the knee
Basic science Articular cartilage is a thin layer of highly specialised connective tissue with complex viscoelastic biomechanical properties. It provides a smooth, lubricated surface for articulation and facilitates the transmission of loads to the underlying subchondral bone. Articular cartilage is historically described as avascular, alymphatic and aneural, and as such has a limited capacity for intrinsic healing and repair. Hyaline articular cartilage is 2e4 mm thick and is composed of a dense extracellular matrix (ECM) composed of water, collagen (predominantly type 2), proteoglycans, non-collagenous proteins and glycoproteins. The cellular component consists of specialised chondrocytes. Three zones of articular cartilage are recognised: superficial (10%e20% of volume), middle (40%e60%), deep (30%) and the calcified zone (Figure 1). The superficial zone protects the deeper layers from shear stresses and the collagen fibres are aligned parallel to the surface to facilitate this. The middle zone has obliquely oriented collagen and resists compressive forces. The deep zone provides the greatest resistance to compressive stresses and the collagen fibres here are arranged perpendicular to the articular surface. This zone has the highest proteoglycan content and the lowest water content. The calcified layer anchors the collagen fibrils of the deep zone to the subchondral bone. Chondrocytes are metabolically active and are derived from mesenchymal stem cells that play a role in the development, maintenance and repair of the ECM. A deep laceration to articular cartilage (through the tidemark between the deep and calcified zones) leads to fibrocartilaginous healing from undifferentiated mesenchymal cells. This response is initiated by bleeding, haematoma and stem cell migration. The resultant cartilage is largely type 1 collagen, which has inferior biomechanical properties to resist wear. A superficial laceration leads to some degree of chondrocyte proliferation but limited healing. Chondral injury, usually from trauma or degeneration, can result in mechanical knee symptoms, pain and functional impairment and ultimately premature secondary osteoarthritis.
James Donaldson Francois Tudor Ian D McDermott
Abstract Chondral damage within the knee of young patients remains a challenge to orthopaedic surgeons, with the chance of resulting mechanical symptoms limiting activity and the risk of progression to osteoarthritis. There are a number of different treatment options which utilize one of two principles for filling chondral defects: either bone marrow stimulation leading to fibrocartilaginous repair or transplantation of mature hyaline cartilage into the defect. In this article we review the current treatment options for symptomatic chondral damage within the knee, discussing the basic science, techniques involved and the evidence supporting each method.
Keywords cartilage transplant; chondral damage; chondroplasty; microfracture
Introduction Articular cartilage damage is commonly seen in the elderly as part of the pathological process of arthritis, and can relatively easily be managed with arthroplasty when symptoms are sufficiently severe. Articular cartilage damage in the younger population is a far more challenging dilemma. Arthroplasty in active, younger patients often gives inferior outcomes and results in premature implant failure rates due to the higher functional demands being placed on the implant. It is therefore vital for orthopaedic surgeons to be aware of the different options available for the treatment of cartilage injuries in order to delay the onset of symptomatic arthritis and the need for joint replacement surgery.
Microfracture Microfracture is a well-established procedure and one of the most widely used treatment techniques for chondral lesions of the knee. It was developed by Steadman1 and is a form of bone marrow stimulation. It is performed arthroscopically and is a relatively simple procedure. It also has low costs compared to other treatment modalities. The primary indication is for full thickness articular cartilage defects on the femoral condyles without significant bone loss (Outerbridge grade 3e4) measuring less than 2e4 cm. The procedure involves debridement of all unstable articular cartilage around the defect down to subchondral bone. Crucial to the repair process is creating a contained lesion with vertical edges of stable cartilage surrounding it. Multiple perforations of the subchondral plate are performed in order to promote bleeding and create a stable blood clot containing mesenchymal stem cells within the lesion. Holes are made perpendicular to the defect a few mm apart, starting peripherally (Figure 2a). A sufficient depth must be drilled or perforated to reach the bone marrow (Figure 2b). This is confirmed when the tourniquet is
James Donaldson MBBS BSc FRCS (Tr & Orth) Fellow, Lower Limb Reconstruction & Arthroplasty, Holland Orthopaedic & Arthritic Centre, Sunnybrook Health Sciences, Toronto, Canada. Conflict of interest: none declared. Francois Tudor MBBS MSc FRCS (Tr & Orth) Fellow, Lower Limb Reconstruction & Arthroplasty, Holland Orthopaedic & Arthritic Centre, Sunnybrook Health Sciences, Toronto, Canada. Conflict of interest: none declared. Ian D McDermott MBBS MS FRCS (Orth) FFSEM (UK) Consultant Orthopaedic Surgeon, London Sports Orthopaedics, Honorary Professor Associate, Brunel University, London Sports Orthopaedics, London, UK. Conflict of interest: none declared.
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MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS
smaller lesions (<4 cm2).8 Long-term quality data is lacking,9 but even with meticulous patient selection and technique, studies suggest the initial clinical effectiveness is reduced after 24 months.6,10,11 The most common problem that can lead to poorer outcomes is bony overgrowth and its incidence has been reported as between 25 and 49% in different studies.5,12 Numerous adjuncts to microfracture have also been described to improve the stability of the initial clot and the subsequent infilling of the chondral lesion. Biomembranes or scaffold devices,13,14 thrombogenic and adhesive polymers,15 growth factors,16,17 hyaluronic acid viscosupplementation,18 stem cells19 and platelet rich plasma20 have all shown some benefit in animal or lab studies but remain to be proven in the human population.
Abrasion arthroplasty Figure 1 Articular cartilage structure.
Arthroscopic abrasion arthroplasty was introduced over 30 years ago as an alternative to existing open procedures. It involves debridement of the inflamed and degenerate tissues, as well as abrasion of the sclerotic exposed bone to expose viable bone and surface vascularity. In the earlier version of this technique, multiple superficial dimples were created in the sclerotic subchondral bone to produce areas of fibrocartilaginous repair. The technique was subsequently extended to removing the entire superficial layer of the subchondral bone plate, resulting in fibrocartilage repair over the entire lesion.21 This repair has some of the properties of articular cartilage (similar to microfracture) but again differs biomechanically. Post-operatively patients need to remain non-weightbearing for 2 months to protect the blood clot from dislodging during the tissue maturation phase. Historically this procedure was used for older patients with degenerative joint disease who did not want a joint replacement. It may also be combined with a realignment procedure if indicated. Results have been variable and often are not comparable between groups due to differing indications, patient heterogeneity, case selection, surgical technique, depth of abrasion and post-operative regimens.22e24
deflated at the end of the procedure and fatty droplets are noted to be coming from the channels. Typical microfracture holes on the medial femoral condyle Penetration of subchondral bone with the microfracture awl The mesenchymal stem cells are able to differentiate into fibrochondrocytes, which contribute to fibrocartilaginous repair over the first few weeks. This fibrocartilage contains more variable types of collagen and has inferior biomechanical properties to native hyaline cartilage. The post-operative regime is demanding for the patient, but thought to be vital for success. Non-weight bearing and continuous passive motion at 0e60 degrees only is permitted in the first 6 weeks. This is thought to improve cartilage nutrition and stimulate mesenchymal stem cell differentiation.2,3 Full return to activities is usually permitted at 3 months. Published results are variable. Steadman et al. reported the follow-up of 71 patients for an average of 11 years.4 All patients were under 45 years of age, had full thickness defects and no other intra-articular pathology. At the final follow-up, significant functional improvements were noted using multiple outcome measures. Similarly, Mithoefer et al.5 found a good to excellent results in 67% of patients at a mean of 3.6 years after the operation. Better outcomes have been observed in younger patients,6 in particular those under 40 years of age7 and in those with
Autologous chondrocyte implantation (ACI) ACI is a two-stage tissue engineering procedure that was originally performed by Brittberg and Peterson25 in 1987. The first stage consists of an arthroscopic biopsy of hyaline articular cartilage from a non-weightbearing portion of the knee.
Figure 2 Diagramtatic representation of microfracture of the medial femoral condyle (2a) and magnified view showing subchondral bone penetration (2b).
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MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS
Unlike microfracture and other marrow stimulation techniques, the goal is to achieve hyaline cartilage coverage. Roberts et al.27 demonstrated 22% hyaline cartilage cover, 48% mixed hyaline and fibrocartilage and 30% fibrocartilage. Peterson et al.28 evaluated 62 femoral condyle grafts and showed that 73% had a hyaline-like appearance at arthroscopy and 67% had histological hyaline characteristics. Zaslav et al.29 prospectively assessed the effectiveness of ACI in 126 patients with previously failed interventions for articular cartilage defects of the knee. 76% were deemed to have a good clinical result at a mean follow-up of four years. The results did not differ if the patient had previously had debridement or a marrow stimulation procedure. Poorer outcomes are associated with a raised BMI, smoking, age over 50 years, worker’s compensation and prolonged duration of symptoms.30e32
Chondrocytes are extracted from the biopsy and expanded in culture. These chondrocytes are then re-implanted into the chondral defect during a second-stage open procedure following debridement of the damaged articular surface. As with microfracture, a stable cartilage rim is required to house the transplanted cells. ACI techniques have evolved over time. First generation ACI involved the use of a periosteal flap (ACI-P) or a Type I/III collagen sheet (ACI-C) sutured to the surrounding cartilage to create a contained reservoir for the chondrocyte cell suspension (Figure 3). Second generation techniques used bio-absorbable scaffolds or matrices containing the autologous cells that were then held in place by fibrin glue (e.g. matrix associated ACI or MACI). The more recent third generation techniques use a tissue engineered three-dimensional cartilage cell graft aiming to give a more uniform seeding of the cultured chondrocytes. Post-operatively, the patient is managed fully weight bearing in a knee brace fixed in extension for one week. Progressive flexion and extension exercises are then introduced to provide a chondrogenic stimulus, with the aim of achieving a full range of movement by 6 weeks. Indications are similar to microfracture: full thickness articular cartilage defects in patients less than fifty years old in the absence of malalignment, instability, osteoarthritis or rheumatoid arthritis. In some centres the procedure has been combined with re-alignment surgery and/or ACL reconstruction in either one or two stages and/or meniscal allograft transplantation. Initial outcomes were reported by Brittberg et al. in 1994.25 Satisfactory to good clinical outcomes were published in patients with a mean follow-up of 39 months. Biopsies showed that eleven of fifteen femoral and one of the seven patella transplants had the appearance of hyaline cartilage. Peterson et al.26 reported the two-to nine-year functional and histological data of 101 patients treated with ACI, demonstrating good to excellent results in isolated femoral lesions (67%), osteochondritis dissecans (89%), the patella (65%) and femoral condyle with ACL reconstruction (75%). Histological analysis of 37 specimens showed the formation of hyaline-like tissue in those achieving good to excellent results.
Radiofrequency chondroplasty In recent years radiofrequency (RF) energy has become a popular tool during knee arthroscopy to debride and contour rough and irregular edged articular cartilage defects. A RF probe produces a plasma field as a result of electrolyte oscillation and a localised heating effect through molecular friction.33 Between 40 and 70 C the collagen in the articular cartilage becomes denatured. As it cools, new bonds are formed creating fibres arranged more parallel to the joint surface.34 It is thought these fibres may be more resistant to shear stress and subsequent degradation compared to a surface left by mechanical debridement alone. Despite the biological arguments, clinical results and data are relatively lacking. There are also potential side effects of RF energy including chondrocyte death and osteonecrosis from excessive heat production. Most recently two studies (one a randomised prospective RCT, the other a prospective review of RF chondroplasty) showed no evidence of any increased risk of osteonecrosis compared with mechanical debridement alone.35,36 In the United Kingdom the National Institute for Health and Care Excellence (NICE) has suggested RF chondroplasty is beneficial, at least in the short-term, for symptomatic discrete, chondral defects, with no major safety concerns. In addition Spahn et al.37 reported improvements at 4 years post-operatively in knee scores, need for further surgery and progression of disease in the RF group compared to the mechanical debridement group.
Autologous matrix-induced chondrogenesis (AMIC) AMIC combines the microfracture and bone marrow stimulation method described by Steadman with a collagen I/III matrix (Chondro-Glide, Geistlich Pharma AG, Wolhusen, Switzerland) that serves to act as a scaffold for new cells. It was first described by Behrens et al. in 2003.38 The blood clot formed in microfracture is fragile and has little ability to withstand tangential forces. An implanted collagen matrix scaffold over the prepared cartilage defect is used in AMIC to improve the mechanical stability and provide a better platform for cartilage repair. Only one stage is needed, there is no donor site morbidity and it is more cost effective than ACI.39
Figure 3 Intra-operative photograph of cell injection during ACI-C. Reproduced with permission. Treating articular cartilage injuries of the knee in young people. BMJ 2010; 340: 998. Macmull S, Skinner J, Bentley G, Carrington R, Briggs T.
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MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS
scaffold for stem cell differentiation. Data and long-term outcomes are minimal.43,44
The procedure can be done open or arthroscopically. The chondral defect is prepared in much the same way as for microfracture. The collagen membrane is then appropriately sized and circles of it are placed in the cartilage defect (Figure 4a). Fibrin glue is applied to all membrane covered areas (Figure 4b and c) and the knee is flexed and extended to check the membrane stability. Published outcomes are limited. In a follow-up of 27 patients an improvement in all clinical scores was seen in 87% of patients40 and follow-up MRI analysis showed moderate to complete in-filling. A recent prospective study of 17 patients showed that 13 of the patients were satisfied or extremely satisfied.41 Gille et al.42 assessed 57 patients with a mean defect size of 3.4 cm at two years follow-up. They found significant improvements in the Lysholm score at 1 year and further improvements at 2 years.
Autologous osteochondral transplantation (osteoarticular transfer system [OATS] or mosaicplasty) This technique involves transplanting multiple small cylindrical autogenous osteochondral plugs from a non-weightbearing, peripheral part of the knee to the articular cartilage defect (Figure 5). The procedure is done in a single stage, either open or arthroscopically. There are commercial kits available which aim to transplant a plug 1 mm bigger than the recipient hole to achieve a press fit. The procedure is limited by the availability of graft that can be harvested, potential differences in structure, thickness and contours between donor and recipient cartilage, as well as graft subsidence. In addition, absence of fill and the potential dead space between plugs may limit the quality of the repair. Clinical use began in 1992.45 Indications include full thickness defects less than 4 cm.2 The largest series of 831 mosaicplasties was published by Hangody and Fules.46 They reported good to excellent results for 92% of femoral lesions, 87% of tibial lesions and 79% of patellofemoral lesions. 80% of the second look arthroscopies demonstrated congruent gliding surfaces and histological
Chondrotissue Chondrotissue is similar to AMIC. It involves a one-step procedure whereby a cell free scaffold of polyglycolic and hyaluronic acid is inserted after bone marrow stimulation. It theoretically offers protection of the bleeding bone and prevents dispersion of the mesenchymal stem cells into the joint, as well as providing a
Figure 4 AMIC. (a) The membrane matching the cartilage defect. (b) and (c) The membranes covered with tissue glue. Reproduced with permission from Surg Sports Traumatol Arthrosc 2012; 20: 922e925. Tomasz Piontek, Kinga Ciemniewska-Gorzela, Andrzej Szulc, Jakub Naczk, Micha1 S1omczykowski. Allarthroscopic AMIC procedure for repair of cartilage defects of the knee.
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Conclusion The treatment of articular cartilage lesions remains a challenge and remains controversial. There are a number of treatment options for symptomatic chondral defects in the knee. Procedures either involve some form of bone marrow stimulation in an effort to recruit mesenchymal stem cells and a fibrocartilaginous repair, or cartilage transplant with the hope of forming new hyaline cartilage. Outcomes for each technique vary and quality data is lacking. Knutsen et al.57 found no difference between ACI and microfracture; Bentley et al.58 found better results for ACI than OATS; Horas et al.59 reported better clinical histological and clinical results with OATS compared to ACI. The only study by a single surgeon comparing microfracture, ACI and OATS was performed and published by Lim et al.60 Post-operative functional examination, follow-up MRI appearances and arthroscopic evaluation, were all used to compare the treated patients. Seventy knees were assessed in patients with isolated cartilage defects and otherwise normal knees. All three procedures showed improvements in functional outcome scores but there was no observable difference in clinical scores, range of movement, follow-up MRI or arthroscopic appearance between the groups. A systematic review in 2011 compared studies on the current treatment of chondral defects of the knee.61 The authors noted there was little level one or two evidence and that studies were often difficult to compare due to heterogeneity and unvalidated scores. They concluded no evidence-based results could be defined between the treatment groups for articular cartilage repair. Each technique has its own advantages and disadvantages and the choice ultimately depends on the surgeon’s preference and familiarity. It is also important to assess and treat any other co-existing pathology such as malalignment, patellar maltracking or bone defects. A
Figure 5 Autologous osteochondral transplantation.
evidence of hyaline cartilage. Similarly, Ozturk et al.47 showed 85% good to excellent results and excellent fill in 84% on MRI.
Osteochondral allografts The use of massive osteochondral allografts remains a salvage procedure following failed previous therapies for large chondral or osteochondral lesions, or where there is extensive bone loss and it is felt that a total knee replacement is not appropriate. A cadaver graft consisting of intact viable articular cartilage and its underlying subchondral bone are transplanted into the defect. It is an expensive procedure and is technically demanding. Graft availability may also be limited, particularly in the UK. There is a risk of disease transmission, immunological rejection and possible incomplete graft incorporation. Grafts can be fresh, cryopreserved or fresh-frozen. Fresh allograft is histologically and functionally preferred48 and should be implanted within 24 days.49 Fixation can be achieved with internal fixation for larger asymmetric grafts or for regular contained defects the press fit plug technique can be used. A number of studies have confirmed the long-term survival of donor chondrocytes after transplantation,50,51 likely due to the relative immunoprivilege of the avascular hyaline cartilage. Williams et al.52 showed in retrieval specimens at an average survival of 42 months that the allograft bone was necrotic but being replaced by creeping substitution, which provided a stable platform for the transplanted articular surface. Gross et al.53 reported 95% survival at five years, 85% survival at ten years and 74% at fifteen years for post-traumatic disease in the femoral condyles. Inferior results were seen with tibial allografts. The authors suggested that a high density of viable chondrocytes and mechanical stability of the allograft are crucial for long-term survival. Similarly, Levy et al.54 demonstrated improvements in pain and function of 129 transplants of the medial femoral condyle as well as 82% survival at ten years. Outcomes from other studies show inferior results in primary osteoarthritis, inflammatory arthropathy, limb malalignment, workers’ compensation and bipolar knee lesions.55,56
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Please cite this article in press as: Donaldson J, et al., (ii) Treatment options for articular cartilage damage in the knee, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.11.009
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Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Donaldson J, et al., (ii) Treatment options for articular cartilage damage in the knee, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.11.009