Wharton’s Jelly in Regenerative Joint Therapy: A Case for IND-Exempt Inclusion in Randomized Controlled Trials

Platelet-rich plasma (PRP) and Wharton’s jelly (WJ) remain two of the most widely explored biologic injectables for the treatment of degenerative joint disease. To date, only PRP is permitted in randomized controlled trials (RCTs) without FDA oversight under an Investigational New Drug (IND) application. This regulatory disparity persists despite the fact that WJ, particularly in its acellular or lyophilized form, shares critical biological, biochemical, and biomechanical functions with PRP—including anti-inflammatory, viscoelastic, and extracellular matrix (ECM) remodeling properties. This article reexamines the native role of WJ during fetal development—where it withstands physiologic strain, undergoes active remodeling, and supports vascular integrity—as the appropriate frame through which to assess its clinical utility in adult joint degeneration. When used intra-articularly, WJ performs the same basic structural and reparative functions required of cartilage matrix support, making its exclusion from homologous use designation a contradiction under the FDA’s own regulatory logic. We argue that WJ, when minimally manipulated and applied for the structural repair of degenerated joints, qualifies as a homologous-use allograft under 21 CFR 1271.3(c). As such, it should be exempt from IND requirements in the context of randomized, controlled, or comparative clinical trials. Enabling such studies is not only scientifically and ethically justified—it is essential to fulfill medicine’s obligation to pursue truth through evidence. RCTs are the cornerstone of clinical validation, and they must be equally accessible for all biologic candidates with plausible mechanistic parity. At stake is not just regulatory fairness, but the future of non-operative care for millions of Americans suffering from joint degeneration.