in adults , damaged cartilage has a very limited capacity for self - healing due to the absence of blood vessels , the low intrinsic density of chondrocytes , and the low turnover of the extracellular matrix .
the absence of stem cells and the low capacity of resident chondrocytes to migrate and proliferate also reduce cartilage regeneration capacity . therefore , numerous methods have been proposed to repair cartilage defects in young or osteoarthritis ( oa ) subjects .
intrinsic repair can be stimulated by bleeding induced by drilling or microfracturing the subchondral bone .
fibrin clot formation , vascular invasion , and recruitment of stem cells into the defect result in the formation of scar tissue that is inferior biomechanically to normal cartilage and susceptible , therefore , to degeneration . in osteochondral transplantation ( or mosaicplasty ) , osteochondral plugs are transferred from undamaged and relatively non - weight - bearing regions to a debrided site .
however , studies have shown that this technique results in donor site morbidity and extensive chondrocyte death in the margins of the osteochondral plugs .
one option to treat focal cartilage lesions is autologous chondrocyte implantation ( aci ) , a procedure developed in the late 1980s to treat traumatic and symptomatic cartilage lesions in the knees of young adults .
the idea behind the aci procedure is to take a cartilage biopsy from the knee by arthroscopy , to isolate cells and grow them in the lab and , once millions of cells have been grown , to implant them into the area of cartilage damage beneath a periosteal flap or a collagen sheet sutured to the surrounding healthy cartilage rim .
more recently , matrix - assisted autologous chondrocyte implantation ( maci ) has been proposed as an alternative to aci .
this technique uses a biomaterial as a chondrocyte carrier that is directly implanted in the lesion [ 3 - 5 ] .
the matrix can be synthetic , including but not limited to poly(lactic acid ) , poly(glycolic acid ) , poly(lactic - co - glycolic acid ) copolymer , poly(ethylene oxide ) , or poly(propylene oxide ) polymers that all gel at body temperature , ceramic composite and hydrogel - containing polyethylene glycol polymer - based derivatives , or natural substances such as fibrin , collagens , alginate , agarose , chitosan , and hyaluronic acid .
these substances have been used to design and produce scaffolds in a rich variety of configurations , including woven and non - woven meshes , sponges , foam , glues , bilayer or trilayer composites   and , more recently , small - size magnetic beads . to promote chondrogenesis ( differentiation to chondrocyte - like cells ) and scaffold integration ,
many maci systems using growth factors , either attached to the scaffolds or through recombinant expression , have been proposed .
several studies have also shown that pulsed electromagnetic field and continuous passive motion may promote chondrogenesis and implant integration to the existing cartilage .
until now , aci / maci techniques have been reserved for patients who meet the following criteria : age 15 - 60 years ; body mass index ( bmi ) 35 ; presence of disabling pain and/or knee locking ; focal articular cartilage defect down to but not through the subchondral bone on a load bearing surface of the femoral condyle ( medial , lateral , trochlear ) ( not in the patella ) ; size of defect < 7 mm in depth , < 6 cm in length , and 1.6 - 10 cm in area ; stable knee with intact meniscus and normal joint space on x - ray ; no active inflammatory or other arthritis , clinically and by x - ray ; procedure is not being done for treatment of degenerative arthritis ( oa ) ; failure of conservative therapy ( minimum of 2 months of physical therapy ) as well as established surgical interventions ( i.e. , microfracture , drilling , abrasion ) - diagnostic arthroscopy , lavage , or debridement are not considered adequate to meet this criterion ; cooperation with post - operative weight - bearing restrictions and activity restrictions together with a potential for completion of post - operative rehabilitation ; and informed consent with realistic expectations .
currently , aci is contraindicated in oa because the risks of complications and failure are high and clinical superiority has not been demonstrated compared with other treatments . in young adults with traumatic chondral lesions ,
re - operation is a common sequel of aci with an incidence of 15 - 30% .
periosteal hypertrophy and delamination , which account for 22.1% and 17.7% , respectively , of adverse effects reported to the us food and drug administration , frequently require aci site debridement .
failure of aci occurs in 4 - 22% of patients depending on defect traits and duration of follow - up .
a study of single condylar defects reported 5% failure at 2 years , which increased to 22.5% at 5 years .
one comparison of aci by patient age demonstrated good to excellent results in 85.7% of patients younger than 20 years compared with 55.9% in those older than 40 years .
recently , an extensive case report has shown that maci based on a bioresorbable two - component gel - polymer scaffold is effective for the treatment of focal degenerative cartilage defects of the knee in subjects between 25 and 50 years of age .
this product is composed of fibrin and a polymer - based scaffold of polyglycolic / polylactic acid ( polyglactin , vicryl ) and polydioxanone . in this study , 18 patients with preoperatively radiologically confirmed oa and a kellgren - lawrence score of 2 or more were included and followed up for 4 years .
the average age of patients ( 8 females and 10 males ) was 35 years ( 25 - 50 years ) , the mean bmi was 25 ( ranging from 19 to 24 ) and mean defect size was 4 cm ( 2 - 6 cm ) .
clinical improvement has been assessed by different scoring systems , including the lysholm and international cartilage repair society ( icrs ) scores and the knee injury and osteoarthritis outcome score ( koos ) .
after 1 year , mean scores improved between 30% and 50% compared with the pre - operative situation , depending on which score was analyzed .
the clinical results 1 year after implantation of the scaffold were good and remained stable for at least 4 years .
this indicates a significant decrease in pain and disability as well as a significant increase in quality of life .
however , nine patients were subjected to second - look arthroscopy due to symptoms such as persistent grinding , catching pain , or swelling .
magnetic resonance imaging performed 4 years after transplantation in 17 patients showed a complete filling of the defect with cartilage repair tissue in 11 patients . in five patients ,
the defects were filled more than 50% and one patient showed a defect fill of less than 50% .
the cartilage signal in 16 out of 17 defects was normal or showed a slight alteration of the signal .
strong to moderate subchondral edema was evident in 6 patients , and 11 out of 17 patients showed no or mild edema .
no to mild knee joint effusion was evident in 12 out of 17 patients treated at 4-year follow - up .
these results are promising but need to be reproduced in older patients with chondrocytes affected by the aging processes . in a retrospective study by minas et al . , 56 patients 45 years of age were treated with aci using periosteal flap .
the mean transplant size was 4.7 cm per defect ( range , 1 - 15 cm ) and 9.8 cm per knee ( range , 2.5 - 31.6 cm ) .
there were eight failures ( 14% ) , mainly in patients receiving workers compensation , and 24 additional arthroscopic surgical procedures for periosteal - related problems and adhesion . at their latest available
follow - up , 72% of patients rated themselves as good or excellent , and 78% felt improved and would again choose aci as a treatment option .
these studies , even if they are limited to prospective or retrospective non - controlled trials , suggest that aci / maci systems could be used to prevent or delay total joint replacement in oa .
these repair techniques are invasive , associated with some complications ( locking of the joint and adhesions , extension deficit , recurrent knee effusion , and so on ) and have an approximately 10% risk of failure .
aci / maci show great promise as treatments for chondral lesions , with a potential for them to be highly cost effective .
but at present this has not been demonstrated and recommendation of this technique for the treatment of cartilage defects in oa joint can not yet be justified .
the superiority of aci / maci compared with other oa treatments , such as hyaluronic acid injection or other surgical procedures ( debridement , microfractures ) , needs to be demonstrated .
further , these methods require a complex process of tissue harvest , cell culture , scaffold implantation and finally post - operative rehabilitation . what are the clinical benefits that justify this investment in oa ?
promising developments are underway with regards to cell - based techniques in combination with scaffolds , growth factors , and gene therapy .
unfortunately , this effort has not been followed by appropriate or sufficient clinical studies to assess these new methods and to compare them with existing systems .
further research is needed to simplify the implantation procedure and to improve the success level .
oa patients are generally older and heavier than the population included in the current studies and we lack data on the incidence of failure in this population .
altogether , the use of aci or maci techniques in oa patients remains experimental but constitutes a real opportunity for such patients in the next decade .
the main problems still to be resolved are how to produce a hyaline cartilage rather than a fibrocartilage , how to facilitate the integration of the repair within the surrounding tissue , and how to simplify the implementation procedure .
 as medical advances lengthen average life expectancy , osteoarthritis ( oa ) will become a larger public health problem - not only because it is a manifestation of aging but also because it usually takes many years to reach clinical relevance . 
 oa is already one of the ten most disabling diseases in industrialized countries . 
 the huge financial burden emphasizes the acute need for new and more effective treatments for articular cartilage defects , especially since there are few disease modifying drugs or treatments for oa . 
 there is no cure for oa and the management of oa is largely palliative , focusing on the alleviation of symptoms . 
 recent longitudinal non - controlled trials suggest that autologous chondrocyte transplantation techniques , which are indicated for young people with traumatic cartilage defects , could also be used in degenerative defects of elderly people with oa . 
 this report discusses this therapeutic opportunity in view of some recently published data . 
Introduction and context
Recent advances
Implications for clinical practice
Competing interest