INCLUSION CRITERIA

1. Age 18-75; diagnosed osteoarthritis in the knee being considered for treatment (study knee).
2. Nonsurgical treatments, such as physical therapy, injections, weight loss, or pain medication, have not helped enough after at least 3 months.
3. X-rays show moderate arthritis in the study knee (KL grade 2-3).
4. MRI shows significant thighbone cartilage damage (Outerbridge grade 3-4), totaling 2-9 sq cm, with at least one area of 2 sq cm or more.
5. BMI of 35 or less.
6. At screening: study knee pain score 40-90/100; other knee pain 30/100 or less; WOMAC daily activity difficulty score 25-90/100 and pain score 40-90/100.
7. Willing to avoid other study knee treatments through the final follow-up and follow pain medication restrictions. Acetaminophen for breakthrough pain and certain postoperative medications are allowed. All pain medications must be stopped at least 48 hours before baseline and follow-up visits, as instructed.
8. Severely high blood pressure must be controlled before surgery. Lab results must be acceptable to the study doctor.
9. Able to follow rehabilitation, visits, and study instructions; use adequate birth control if able to become pregnant; and provide written consent.

EXCLUSION CRITERIA

1. Injection into either knee within 3 months before consent involving hyaluronic acid, PRP, bone marrow products, steroids, or an investigational drug. Other-knee injections are allowed during the trial.
2. Imaging shows disqualifying arthritis, bone, cartilage, or meniscus findings, including:

• Study knee KL grade 0, 1, or 4; other knee KL grade 4.
• Bow-legged or knock-kneed alignment of at least 6 degrees in either knee.
• Severe ligament instability (grade 3 or higher) or instability needing surgery.
• Complete meniscus loss, root tears, or severe displacement.
• Severe cartilage damage on opposing joint surfaces exceeding 25% of the thighbone lesion area and/or extending through underlying bone.
• Severe bone marrow lesions outside the thighbone treatment area, bone tissue death, fractures, bone bruises, tumors, infection, abnormal bone marrow tissue, or a cyst over 4 mm at the treatment site.

1. Study knee surgery within 6 months, incomplete recovery from earlier surgery, or prior radiation to that knee.
2. Prior cartilage repair, partial knee replacement, implants, or other invasive arthritis treatments in the study knee. Prior microfracture may be allowed if the underlying bone is intact without significant bone spurs.
3. Certain inflammatory, autoimmune, genetic, metabolic, blood vessel, or nerve conditions. Examples include rheumatoid arthritis, lupus, gout, fibromyalgia, IBD/IBS, multiple sclerosis, or myasthenia gravis. Celiac disease and varicose veins alone do not exclude participation.
4. Certain infections or blood disorders, including HIV, hepatitis, syphilis, or clotting/bleeding disorders. A deep vein clot at least 5 years before consent does not exclude participation.
5. Blood thinners such as warfarin, Eliquis, Xarelto, or Plavix. Aspirin 81 mg is allowed.
6. HbA1c over 8%; infection needing injected/infused antibiotics; immune-suppressing drugs within 6 months; chemotherapy within 12 months; or prior donor stem cell therapy.
7. Hyaluronan allergy; pregnancy/breastfeeding; current or past psychotic illness or epilepsy; substance/alcohol abuse within 3 years; or inability/unwillingness to have MRI.
8. Current workers' compensation, personal injury, or disability benefits or related litigation.
9. Any other condition the study doctor considers inappropriate.

BASELINE/SURGERY REQUIREMENTS

Baseline pain must remain 40-90/100 and WOMAC function 25-90/100. Surgery must confirm qualifying cartilage damage totaling no more than 9 sq cm. Disqualifying meniscus, opposing cartilage, bone/joint, prior repair, or pregnancy findings prevent treatment.

This is a summary. The study team will review all detailed criteria.