Amniotic and Umbilical Products: Evidence and Regulatory Questions

Amniotic, umbilical-cord, and Wharton's jelly products are marketed and used in orthopedic practice. Patients considering these treatments should understand what these products are, what the evidence shows, and what the regulatory landscape means for their use.

Amniotic membrane: Derived from the innermost layer of the placenta. Amniotic membrane products may be processed as dehydrated, cryopreserved, or fresh tissue. They contain extracellular matrix proteins, growth factors, and cytokines. They do not contain live cells after standard processing.

Amniotic fluid: Contains growth factors, cytokines, and hyaluronic acid. Processed amniotic fluid products are used as injections for joint and soft-tissue conditions.

Umbilical cord tissue: The umbilical cord contains Wharton's jelly, a gelatinous substance rich in mesenchymal stromal cells, growth factors, and extracellular matrix proteins. Umbilical cord tissue products are processed from donated umbilical cords after birth.

Wharton's jelly: The connective tissue matrix of the umbilical cord. Wharton's jelly products contain mesenchymal stromal cells and growth factors. Whether these cells survive standard processing and remain viable after injection is a subject of ongoing scientific debate.

The FDA regulates human cells, tissues, and cellular and tissue-based products (HCT/Ps) under 21 CFR Part 1271. Products that meet specific criteria — including minimal manipulation and homologous use — may be exempt from the full drug approval process. Products that do not meet these criteria require an Investigational New Drug (IND) application or a Biologics License Application (BLA).

The FDA has stated that many amniotic and umbilical cord products used for orthopedic conditions do not meet the criteria for the HCT/P exemption because orthopedic injection is not a homologous use of amniotic or umbilical tissue. This means that, under the FDA's interpretation, these products require BLA approval for orthopedic use — approval that most products do not have.

These products are not FDA-approved for orthopedic conditions. This does not mean they are illegal to use — the FDA has exercised enforcement discretion for certain products while the regulatory framework evolves — but it does mean that the FDA has not reviewed and approved the safety and efficacy data for these specific orthopedic applications.

Patients should not interpret the availability of these products as evidence of FDA approval. "FDA-registered" or "FDA-cleared" are not the same as "FDA-approved."

The clinical evidence for amniotic and umbilical products in orthopedic conditions is limited and of lower quality than the evidence for PRP.

Knee osteoarthritis: A 2018 randomized controlled trial by Vines et al. (Journal of Knee Surgery, 2016; DOI: 10.1055/s-0035-1568988) compared amniotic fluid injection to saline placebo in 45 patients with knee osteoarthritis and found no significant difference in outcomes at three months. A 2019 randomized trial by Farr et al. found amniotic suspension allograft superior to saline at 12 months in a small trial, but this study has been criticized for methodological limitations.

Tendon conditions: Case series and small observational studies have reported improvements after amniotic membrane injection for rotator cuff tendinopathy and plantar fasciitis, but randomized controlled trial data is limited.

Overall assessment: The evidence base for amniotic and umbilical products in orthopedic conditions is insufficient to support strong clinical recommendations. Most published studies are small, lack adequate controls, and have short follow-up periods. The heterogeneity of products — different tissue sources, processing methods, and storage conditions — makes comparison across studies difficult.

These products should not be described as containing live stem cells unless that claim is specifically supported by validated product documentation and legally appropriate regulatory authorization. Standard processing methods for most commercially available amniotic and umbilical products do not preserve cell viability. Marketing claims that these products deliver "live stem cells" to the injection site are not supported by the available evidence for most products.

Before receiving an amniotic or umbilical product injection, patients should ask:

• What is the specific product name and manufacturer?
• Is this product FDA-approved for this specific orthopedic application?
• What is the evidence basis for using this product for my specific diagnosis?
• What are the facility and product costs?

References

• U.S. Food and Drug Administration. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use. FDA Guidance Document, 2017.
• Vines JB, et al. Cryopreserved Amniotic Suspension for the Treatment of Knee Osteoarthritis. J Knee Surg. 2016;29(6):443–450. DOI: 10.1055/s-0035-1568988
• Farr J, et al. A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. J Knee Surg. 2019;32(11):1143–1154.

Reviewed by Joseph Blythe, DO — July 2026 Last medical review: July 31, 2026

For a broader overview of evidence-based orthopedic treatments and injections offered at Blythe Orthopedics & Spine — including PRP, bone marrow aspirate, and peptide services — see the Orthobiologics & Injections page.

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