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Current Concepts in Viscosupplementation: New Classification System and Emerging Frontiers.

Gustavo Constantino de Campos1, Alberto Cliquet1

  • 1Departamento de Ortopedia, Reumatologia e Traumatologia, Universidade Estadual de Campinas, Campinas 13083-887, Brazil.

Bioengineering (Basel, Switzerland)
|October 29, 2025
PubMed
Summary

Hyaluronic acid (HA) injections for osteoarthritis (OA) need better classification. A new framework based on chemical structure, not just molecular weight, clarifies product differences and guides optimal treatment strategies.

Keywords:
classificationhyaluran receptorshyaluronic acidinjectionsintra-articularknee osteoarthritisviscosupplementation

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Area of Science:

  • Orthopedics
  • Biomaterials Science
  • Rheumatology

Background:

  • Viscosupplementation with intra-articular hyaluronic acid (HA) is a primary treatment for osteoarthritis (OA).
  • Current product classification based solely on molecular weight is inadequate, conflating chemically distinct HA formulations.
  • Clinical controversies and outdated classifications hinder effective therapeutic application.

Purpose of the Study:

  • To critically analyze the current landscape of HA viscosupplementation for OA.
  • To propose a new, two-tiered classification framework for HA products based on chemical structure and molecular weight.
  • To evaluate the clinical and biological implications of different HA formulations and combination therapies.

Main Methods:

  • Comprehensive literature review and critical analysis of existing HA viscosupplementation products.
  • Development of a novel classification system distinguishing between linear (non-modified) and cross-linked (chemically modified) HA.
  • Evaluation of the mechanism of action, efficacy, and biological profiles of various HA formulations.

Main Results:

  • A new classification framework separates HA into linear (sub-classified by molecular weight: Low, Intermediate, High) and cross-linked (hydrogels with ultra-high effective molecular weight) categories.
  • High-concentration, high-molecular-weight linear HA demonstrates year-long efficacy and superior chondroprotective biological effects.
  • Linear HA serves as a versatile scaffold for combination therapies with corticosteroids, PRP, bone marrow aspirate, and stromal vascular fraction.

Conclusions:

  • A revised classification of HA products based on chemical structure is essential for understanding their distinct properties and clinical applications.
  • High-molecular-weight linear HA formulations offer significant advantages in efficacy and chondroprotection over traditional cross-linked products.
  • Combination therapies utilizing linear HA as a scaffold represent a promising frontier for advanced OA management.