Current Concepts in Viscosupplementation: New Classification System and Emerging Frontiers

Viscosupplementation with intra-articular hyaluronic acid (HA) is a key therapeutic option for osteoarthritis (OA), yet the field is hampered by clinical controversies and an outdated classification of available products. This comprehensive review critically analyzes the current landscape, moving from a mechanical to a biological paradigm of HA’s mechanism of action. We argue that the traditional HA product classification based solely on molecular weight is insufficient, as it conflates chemically distinct products. Therefore, we propose a new, two-tiered classification framework: the primary distinction is based on chemical structure, separating linear (non-modified) HA from cross-linked (chemically modified) HA. Linear HA is then sub-classified by molecular weight (Low, Intermediate, and High), while cross-linked HA is defined as a separate category of hydrogels with a ultra-high effective molecular weight. Within this clearer framework, we analyze the central controversy between formulations, highlighting the pivotal emergence of high-concentration, high-molecular-weight (>2 million Dalton) linear HA. These formulations not only challenge the durability rationale for cross-linking by providing year-long efficacy but also possess a superior biological profile for chondroprotection, preserving chondrocyte viability and function. Furthermore, we explore the expanding frontier of combination therapies, where linear HA serves as the ideal physiological scaffold for agents like corticosteroids, PRP and other injectable orthobiologics such as bone marrow aspirate and stromal vascular fraction.