Microfragmented Adipose Tissue Compared to Saline Injection for the Treatment of Knee Osteoarthritis

Inclusion Criteria:

• In order to be eligible to participate in this study, participants must meet all ofthe following criteria:

1. Age ≥ 18 years old at the date of screening

2. Have both clinical and radiographic findings consistent with osteoarthritis ofthe knee:

3. Participant has clinical findings including (but not limited to)tenderness to palpation, swelling/effusion, stiffness, chronic limitedrange of motion.

4. Participant has a diagnosis of knee OA defined as Grade 2 to 3 by (K/L)weight bearing X-ray and physician review within the past 3 months.

5. The index knee must present with symptomatic knee pain using WOMAC-A VisualAnalog Scale (VAS) of 40mm or greater despite conservative therapies for 3months prior to enrollment:CONFIDENTIAL Page 12 of 52 Version 2.0, 10JUL2023a. Failure of conservative therapies include the following: Participants musthave failed a minimum of at least 3 months, including (1) physical therapy, and (2) oral OTC pain medications such as an NSAID (Aleve® or Advil®) orAcetaminophen (Tylenol®), or a prescription NSAID, for a period of 90 days atthe Maximum Tolerable Dose according to the respective manufacturer'sinstructions on dose and duration, or their physician's over-riding guidance.Patients who are unable to tolerate this dosing regimen for 90 days, or thosein whom NSAIDS or Acetaminophen are contraindicated, shall be deemed to havesatisfied this inclusion criteria.

6. Willing to give written Informed Consent to voluntarily participate in thestudy and sign the Health Insurance Portability and Accountability Act (HIPAA)Authorization prior to study participation

7. Ability to return for multiple follow-up visits

8. Ability read and understand English language

9. Females of child-bearing potential must have a negative urine pregnancy testperformed within 7 days of study enrollment or be postmenopausal (for at least 2 years) or surgically sterilized (bilateral tubal ligation, bilateraloophorectomy, or hysterectomy)

Exclusion Criteria:

• Participants who meet any of the following criteria will be excluded fromparticipating in this study. Study eligibility of participants reporting isolateduse of prohibited medications during the restricted periods defined by thisprotocol, will be evaluated on a case-by-case basis by the medical monitor.

1. Diagnosis of knee OA defined as K/L grade 1 or 4.

2. BMI greater than 35 kg/m2.

3. Diagnosis of rheumatoid arthritis, psoriatic arthritis, or any other disorderwhich attributes to the primary source of their knee pain, including but notlimited to: osteonecrosis, radiculopathy, bursitis, tendinitis, tumor, cancer.

4. Presence of any clinically observed active infection including in the indexknee joint, infection at the site of adipose tissue harvest, and/or any activesystemic or local infection.

5. Undergone injection in target knee within 6 months prior to screening visit,including but not limited to corticosteroids, hyaluronic acid (HA), bone marrowconcentrate (BMAC), platelet rich plasma (PRP), human cellular exosomes,amniotic fluid, or any human birth tissue.

6. Undergone surgical procedures of either knee within 6 months prior to thescreening visit.

7. Bilateral knee pathology can only be treated in one knee for the study. Thecontralateral knee must have a WOMAC-A Visual Analog Scale (VAS) pain score ofno more than 20mm at the time of screening (48-hr recall).

8. Index knee greater than 10 degrees varus/valgus deformities (anatomictibiofemoral angle).

9. Knee pain associated with osteochondritis dissecans, ligament damage ordisplaced meniscus tear.

10. Current or historical autoimmune disease that requires immunosuppressivemedication.

11. Any disorder affecting musculoskeletal pain and/or function, includingsymptomatic OA of the back, hips, or ankle that would interfere with theevaluation of the treated knee.

12. Planned or expected surgery within the next 12 months.

13. Allergy to lidocaine, epinephrine, or valium.

14. Diagnosis of HIV or viral hepatitis.

15. Use of oral systemic corticosteroids within the last 90 days and for theduration of the study.

16. History of any chemotherapy or radiation therapy of the targeted/treatment legor adipose harvest site.

17. Active worker's compensation case.

18. Diagnosis of coagulation disorders (e.g., Von Willebrand's disease) and/orcurrently on anti-coagulant therapy.

19. Occurrence of knee trauma to the index knee within six months prior toscreening.

20. Unwilling to stop usage of over-the-counter pain medication (e.g.,Acetaminophen or NSAID), "Rescue Analgesics", for 7 days prior to any follow-upvisit, with the exception of one "baby aspirin" per day for cardiovasculartherapy or prophylaxis.

21. Unwilling to stop taking prescription pain or prescription anti-inflammatorymedication for the duration of the study, with the exception of Tramadol duringthe immediate post-procedure period noted below.

22. Unwilling to abstain from NSAIDS for 7 days pre-injection and 2 weekspost-injection. Tramadol is allowed during the 72 hours immediatelypost-injection, with diary documentation of usage.

23. Currently taking prescription pain medication for a condition other than theindex knee.

24. Currently in prison.

25. Untreated symptomatic injury of the index knee (e.g., acute traumatic injury,anterior cruciate ligament injury, clinically symptomatic meniscus injurycharacterized by mechanical issue such as locking or catching).

26. Impossibility to harvest enough adipose tissue.

27. Any medical issue that the clinician feels would be a contraindication to thestudy treatment including, but not limited to:

28. Uncontrolled diabetes defined as HbA1c >7%,

29. History of uncontrolled hypertension defined by average systolic BP >140mmHg or diastolic BP > 90 mmHg on ≥ 3 blood pressure medications,

30. History of cardiovascular disease,

31. History of cerebrovascular disease,

32. Uncontrolled asthma, defined as symptomatic (i.e., shortness of breathand/or wheezing) despite therapy,

33. History of solid organ or hematologic transplantation,

34. Diagnosis of non-basal cell malignancy within preceding 5 years,

35. Change in prescription medication within 1 month prior to enrollment,

36. Clinically significant abnormalities in vital signs at the time ofscreening defined by

• Systolic BP >140 or <90 mmHg or diastolic BP >90 or <60 mmHg
• Pulse <55 or >100 bpm
• Respiratory Rate <9 or >20
• Temperature >99 °F

28. History of septic arthritis or sepsis/bacteremia in the affected knee within 6months prior to screening, or infection requiring antibiotic treatment withinthe preceding 3 months.

29. Women who are breastfeeding.

30. Unwilling to use contraception for 3 months post procedure unlesspostmenopausal (for at least 2 years) or surgically sterilized (bilateral tuballigation, bilateral oophorectomy, or hysterectomy).