DeNovo NT Natural Tissue Graft Stratified Knee Study

Inclusion Criteria:

1. Voluntary signature of the IRB approved Informed Consent,
2. Male or female subjects between the ages of 18 to 55 years,

3. If female:

   • Actively practicing a contraception method and willing to continue for a minimum of 1 year postoperatively, or
   • Practicing abstinence and willing to continue for a minimum of 1 year postoperatively, or
   • Surgically sterilized, or
   • Postmenopausal.
4. Pretreatment arthroscopic confirmation indicating one or two contained lesion(s) of the femoral condyle, trochlear groove, or patella equal to an ICRS Grade 3 or 4, or OCD lesions with healed bone base, which is non sclerotic and no loss of bone greater than 6mm measured from the surrounding subchondral plate,
5. Has peripheral cartilage debridement to healthy cartilage that results in a lesion(s) with an area of > 1 cm2 and ≤ 5 cm2,
6. Lesion(s) to be treated must be contained/shouldered by surrounding native cartilage > 70% of the periphery,
7. Ligaments in the affected knee are stable,
8. Ipsilateral knee compartment has intact menisci (or meniscectomized remnant with > 5 mm rim),
9. The contralateral knee is asymptomatic, stable, and fully functional,
10. Is refractory to conservative non-surgical management (e.g. hyaluronic acid injection, activity modification) or previous minimal surgical intervention (e.g., arthroscopic lavage, debridement) or ACI or marrow stimulation for this condition and is further than 3 months from either the initiation of nonsurgical management or from minimal surgical intervention or is further than 12 months from ACI or marrow stimulation,
11. Must record a response, at the preoperative study visit, of moderate to extreme pain for any one of the KOOS Pain Scale questions, P2 through P9.
12. Must be physically and mentally willing and able, in the Investigator's opinion at the time of enrollment, to be compliant with the protocol - including all follow-up visits, survey completion, weight-bearing restrictions, and post-operative rehabilitation.

Exclusion Criteria:

1. Clinical and/or radiographic disease diagnosis of the indexed affected joint that includes:

   • Osteoarthritis or avascular necrosis,
   • Rheumatoid arthritis, or history of septic or reactive arthritis,
   • Gout or a history of gout or pseudogout in the affected knee,
   • Bipolar articular cartilage involvement (or kissing lesions) of the ipsilateral compartment (i.e., > than ICRS Grade 2 on the opposing articular surface),
   • Has more than two clinically relevant chondral lesion(s) on the index knee,
   • Osteochondritis dissecans of the knee with significant bone loss (greater than 6 mm deep from the subchondral plate).
   • Associated damage to the underlying subchondral bone requiring bone graft,
   • Has well-defined subchondral cyst(s),
   • Has current or impending subchondral avascular necrosis,
2. History of secondary arthropathies (i.e., sickle cell disease, hemochromatosis, or autoimmune disease),
3. Uncontrolled diabetes,
4. Displays a high surgical risk due to unstable cardiac and/or pulmonary disease,
5. Has HIV or other immunodeficient state including subjects on immunosuppressant therapies, or has significant illness (metastasis of any type) that decreases the probability of survival to the 2 year endpoint,
6. Is at substantial risk for the need of organ transplantation, such as renal insufficiency,
7. Is pregnant or breast-feeding,
8. Body Mass Index >35 (BMI=kg/m2),
9. Is participating concurrently in another clinical trial, or has participated in a clinical trial within 30 days of surgery,
10. Is receiving prescription pain medication other than NSAIDs or acetaminophen for conditions unrelated to the index knee condition, chronic use of anticoagulants, or taking corticosteroids,
11. Has a neuromuscular, neurosensory, or musculoskeletal deficiency that limits the ability to perform objective functional assessment of either knee,
12. Active joint infection or history of chronic joint infection at the surgical site,
13. Prior total meniscectomy of either knee,
14. Radiographically has >5 degrees of malalignment as measured from the hip, knee and ankle mechanical axis.
15. Has received, within the past three months intra-articular hyaluronic acid therapy or cortisone injections in the index knee,
16. Has prior tendon repair, meniscus repair, ligament repair or realignment surgery in the affected knee within the past 6 months,
17. Failed marrow stimulation or ACI treatment performed less than 12-months before baseline,
18. Index knee has been surgically treated for cartilage repair with OATs, mosaicplasty or osteochondral allograft,
19. Requires concomitant procedures (i.e., anterior cruciate ligament repair, high tibial osteotomy of the affected knee) with the exception of incidental loose body removal, debridement, synovectomy and/or partial meniscectomy with remaining rim >5mm wide,
20. Has contraindications for Magnetic Resonance Imaging (MRI),
21. Has an allergy to Polymyxin B sulfate or Bacitracin antibiotics,
22. Is receiving workman's compensation or currently involved in litigation relating to the index knee