Phase III Study to Evaluate Safety and Effectiveness of NOVOCART 3D Plus vs. Microfracture in Knee Cartilage Defects

Inclusion Criteria: 1. Patient is between 18 and 65 years old at screening OR (in selected countries only) is a pediatric patient (14-17 years old) with closed epiphyseal growth plate (confirmation of closure of epiphyseal growth plate of the index knee by x-ray or MRI required). 2. Patient has a localized articular cartilage defect of the femoral condyle or the trochlea of the knee. 2 localized cartilage defects are accepted if the total defect size is ≤ 6 cm2 and the size of each individual lesion is ≥ 2 cm2, both cartilage defects are located at the femoral condyle and/or the trochlea and both cartilage defects are to be treated with NOVOCART 3D plus or microfracture. 3. Patient has a defect size is between 2 and 6 cm2. Note: defect size can be estimated by MRI at visit 1 if no data is available from medical history. 4. Patient has an intact articulating joint surface (not higher than Grade 2 International Cartilage Repair Society classification, no kissing lesions). Note: ICRS classification can be estimated by MRI at visit 1 if no data is available from medical history. 5. Patient has an intact meniscus; a maximum of 50% resection is allowed. Note: status of meniscus can be estimated at visit 1 if no data is available from medical history. 6. Patient has a stable knee joint or sufficiently reconstructed ligaments. If not, ligament repair must be done before, during or within 6 weeks after cartilage treatment (ACT/microfracture). 7. Patient has free range of motion of the affected knee joint or ≤ 10° of extension and flexion loss. 8. Patient has a defect-grade of III or IV according to the ICRS classification. Note: ICRS classification can be estimated by MRI at visit 1 if not data is available from medical history. 9. Patient has a baseline score of 60/100 on the 2000 International Knee Documentation Committee (IKDC) subjective knee evaluation. 10. Patient is willing and able to give written informed consent to participate in the study and to comply with all study requirements, including attending all follow-up visits and assessments and postoperative rehabilitation regimen. 11. Mandatory for France only: Patient benefits of a health insurance regimen. Exclusion Criteria (pre-operative): 1. Patient is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study. 2. Patient is unable to undergo magnetic resonance imaging (MRI). 3. Patient has prior surgical treatment of the target knee using mosaicplasty, autologous chondrocyte transplantation and/or microfracture. Note: prior diagnostic arthroscopies with debridement and lavage are acceptable. Ligament repair is accepted, if performed before, during or within 6 weeks after cartilage treatment (ACT/microfracture). 4. Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade \> 2 (see Appendix A). 5. Patient has chronic inflammatory arthritis and/or infectious arthritis. 6. Patient has joint space narrowing \> 1/3 in the target knee when compared to the other knee or smaller than 3 mm joint space measured on x-ray. 7. Patient has malalignment (valgus- or varus-deformity) in the target knee. Note: In suspected cases, the mechanical axis must be established radiographically by complete leg imaging in standing position and in a.p. or rather p.a. projection. The Mikulicz line is not allowed to deviate more than 5 mm of the eminentia intercondylaris. If alignment is necessary, surgery has to be performed before, during or within 6 weeks after cartilage treatment (ACT/microfracture). 8. Patient has prior surgical treatment of clinical relevance of the target knee. 9. Patient has an osteochondral defect. 10. Patient has bilateral lower limb pain or low back pain. 11. Patient has a known systemic connective tissue disease. 12. Patient has a current uncontrolled diabetes. 13. Patient has a known history of autoimmune disease. 14. Patient has a known history of immunological suppressive disorder or is taking immunosuppressants. 15. Patient is currently systemically or intra-articularly taking steroids and/or has used steroids within the last 30 days prior to screening visit 1. 16. The patient has a history of HIV/AIDS. 17. The patient has a history of syphilis (Treponema pallidum). 18. The patient has an active hepatitis B or C infection with verified antigens. Note: Patients with a cured hepatitis B or C infection and/or verified antibodies are not excluded. 19. The patient has at the site of surgery an active systemic or local microbial infection, eczematization or inflammable skin alterations (including protozoonosis: Babesiosis, Trypanosomiasis (e.g. Chagas-Disease), Leishmaniasis, persistent bacterial infections, like Brucellosis, spotted and typhus fever, other Rickettsiosis, Leprosy, Recurrent Fever, Melioidosis or Tularaemia). 20. Patient has a known history of cancer within the past 5 years. 21. Patient has a known history of osteoporosis; also patients with primary hyperparathyroidism or hyperthyroidism without satisfactory treatment, chronic renal failure or patients with prior pathological fractures independent of the genesis are excluded. 22. Patient has any degenerative muscular or neurological condition that would interfere with evaluation of outcome measures including but not limited to Parkinson's disease, amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS). 23. Patient has a body mass index (BMI) higher than 35 kg/m2. 24. Patient is a woman who is pregnant or lactating. Note: contraception is indicated for female patients of childbearing potential until the day of cartilage treatment. Female patients who are unwilling to practice a medically acceptable method of birth control until the day of cartilage treatment cannot be included. 25. Patient is currently participating, or has participated in any other clinical study within 3 months prior to the screening visit. 26. Patient has known current or recent history of illicit drug or alcohol abuse or dependence 27. Patient has psychiatric or cognitive impairment that, in the opinion of the investigator, would interfere with the patient's ability to comply with the study requirements, e.g., Alzheimer's disease. 28. Patient has any other condition, which, in the opinion of the investigator, would make the patient unsuitable for the study. 29. Patient has a history of HTLV. Intra-operative Inclusion Criteria: 1. Patient is not pregnant as confirmed by urine pregnancy test before arthroscopy. 2. Patient has a localized articular cartilage defect of the femoral condyle or the trochlea of the knee. 2 localized cartilage defects are accepted if the total defect size is up to 6 cm2 and the size of each individual lesion is at least 2 cm2, both cartilage defects are located at the femoral condyle and/or the trochlea and both cartilage defects are to be treated with NOVOCART 3D plus or microfracture. 3. Patient has a defect size of 2 to 6 cm2 post-debridement. 4. Patient has an intact articulating joint surface (at least (or higher) Grade 2 International Cartilage Repair Society classification) no kissing lesions). 5. Patient has an intact meniscus; a maximum of 50% resection is allowed (no indication for concurrent meniscus transplant). 6. Patient has a stable knee joint or sufficiently reconstructed ligaments. If not, ligament repair must be done during or within 6 weeks after cartilage treatment (ACT/microfracture). 7. Patient has a defect grade of III or IV according to the ICRS classification.