Temporal Hierarchy of Hydrogels and Orthobiologic Therapies for Knee Osteoarthritis

Knee osteoarthritis is commonly managed with intra-articular therapies that differ widely in composition, mechanism, and clinical persistence, yet the duration of their benefit is discussed inconsistently, which limits practical comparison between ozone, hyaluronic acid, platelet-derived products, and cell-rich orthobiologics. In this narrative review we examine the mechanism-driven temporal behavior of these therapies, focusing on the physicochemical, biomechanical, biological, and regenerative factors that influence how long a clinical response persists. By temporal hierarchy we mean the mechanistically informed pattern by which therapies differ in the duration of their physicochemical presence, biological activity, and clinical benefit, not a ranking of efficacy or a claim of equivalence. Read against this definition, ozone occupies the shortest end of the spectrum; conventional hyaluronic acid shows intermediate persistence; modified hyaluronic acid hydrogels may extend activity through improved rheology and enzymatic resistance; platelet-rich plasma and injectable platelet-rich fibrin provide more sustained biological signaling; and bone marrow aspirate concentrate and stromal vascular fraction may act over longer periods through trophic and paracrine pathways. Heterogeneity in study design, patient selection, and outcome reporting still limits firm conclusions, and standardized reporting of product characteristics and time-related endpoints will be essential to validate or refine the proposed framework.