Inclusion Criteria:  Signed written informed consent Willing to be randomized to either the investigational or control group Male or female at least 18 years of age and less than 80 Clinical diagnosis of symptomatic tibiotalar (ankle) OA (primary idiopathic OA or post-traumatic OA), modified K-L grade 1-3a One ankle is the most symptomatic lower extremity joint and the only lower extremity joint currently planned for treatment Willing and able to comply with all study requirements including all postoperative clinical and radiographic evaluations For women of childbearing potential (not post-menopausal for 12 months or surgically sterile), a urine pregnancy test with a negative result must be obtained at screening and on the day of procedure, prior to injection Male and female trial participants must commit to adequate birth control (e.g., surgically sterilized, oral contraceptive, two methods of barrier birth control, or abstinence) through the final follow-up Chronic ankle pain for ≥ 6 months SAOS Pain score ≥ 30 and ≤ 80 and AOS Function score ≥ 30 and ≤ 80 Willing to discontinue all prescription and over-the-counter pain medications being used for ankle OA symptoms for the duration of the study, except for acetaminophen, which is not allowed for the 3 days preceding each scheduled follow-up visit and the day of the follow-up visit.  Exclusion Criteria:  Previously received intra-articular injections in the index joint of Axolotl Ambient, bone marrow aspirate concentrate (BMAC), platelet-rich plasma (PRP), or other biologic-based products within the last 12 months. Modified K-L Grade 3b or 4 osteoarthritis of the index joint Diagnosis of ipsilateral peri-articular arthritis (e.g. subtalar joint) that the investigator determines may significantly confound the study results Received intra-articular hyaluronic acid injection in the index joint within the last 6 months Received intra-articular steroid injection in the index joint within the last 3 months Prior major surgical repair or reconstruction of the ankle that the investigator determines may significantly confound the study results Baseline pain catastrophizing score ≥ 23 Any surgery of the index ankle within the last 12 months Planned arthroscopy or other procedure on the ankle during the study Bilateral ankle OA requiring treatment of both ankles Pregnancy, breastfeeding, or woman of child-bearing potential not using adequate contraception Bone deficit Charcot foot disease Radiographic evidence of open epiphyses Systemic inflammatory condition Substantial vascular insufficiency Current treatment with anticoagulants Deformity in coronal, axial or sagittal plane greater the 30° Patients weighing less than 47 kg. BMI greater than 45 kg/m2 Documented medical history of, or radiographic evidence of, a bone disease (e.g. severe osteoporosis or avascular necrosis) or other condition (e.g., osteolysis) Comorbidity that would limit the ability to administer any functional measurements Has at the time of injection, a systemic or local infection at the site of injection Medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the study or potentially decrease survival or interfere with ambulation or rehabilitation (e.g., history of transient ischemic attack, stroke or liver disease) Known hypersensitivity to penicillin Known allergy to phenol red Currently receiving treatment with a drug known to interfere with bone or cartilage metabolism [e.g., systemic steroid therapy (topical steroid therapy is permissible), methotrexate] Medical condition requiring radiation, chemotherapy or immunosuppression Have an active history of malignancy (except for basal cell carcinoma of the skin) Has a history of autoimmune disease known to affect bone or cartilage. Examples include spondyloarthropathies (e.g., ankylosing spondylitis, Crohn's disease, and ulcerative colitis), Juvenile Arthritis, rheumatoid arthritis, Grave's disease, and Hashimoto's thyroiditis Has obvious or documented alcohol or illicit drug addictions Is a prisoner in a correctional institution/facility Actively involved in litigation or workman's compensation Has participated in clinical studies evaluating investigational devices, pharmaceuticals or biologics within 6 months of randomization Bedridden, confined to a wheelchair, or unable to walk 50 m without the help of a walker, crutches, or cane Is currently taking prescription pain medication for any conditions other than ankle osteoarthritis.