{
  "abstract": "Hyaluronan-based materials are widely described as hydrogels, yet the term is applied without distinction to preparations that differ fundamentally in structure. This review addresses that imprecision by separating three material states of hyaluronan and by stating the criteria under which each may be called a gel: native linear hyaluronan, which forms a viscoelastic solution; the hexadecylamide derivative (HYADD-4), which self-assembles into a transient physical network through hydrophobic interactions; and hyaluronan cross-linked with 1,4-butanediol diglycidyl ether (BDDE), which forms a covalent three-dimensional network. A material is treated as a gel here only where both a percolated network and a solid-like mechanical response are documented. On that basis the covalent network qualifies; the derivative is elastic-dominated across the walking-to-running frequency band of the knee but has not been subjected to a formal Winter-Chambon analysis and is therefore described as gel-like; and the linear solution does not qualify at the molecular weights and concentrations used in marketed viscosupplements. We review the chemistry of network formation, the comparative physicochemical and rheological behavior, including viscosity, the storage and loss moduli, boundary lubrication, and resistance to enzymatic and oxidative degradation, and the receptor-mediated and anti-inflammatory mechanisms of action involving CD44 and molecular-weight-dependent signaling. Clinical and regenerative applications in osteoarthritis viscosupplementation and in scaffolds and carriers for cells and growth factors are summarized for each state. The networked materials show higher viscoelasticity and greater resistance to degradation than the linear solution, which provides a rationale for longer residence; the evidence for a clinical advantage over conventional hyaluronan, however, rests largely on preclinical and rheological data. A three-state framework is proposed, pending validation, to support clearer interpretation of the literature and more rational material selection.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, FC Sports Traumatology, Salvador 40296-210, BA, Brazil.",
    "Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil.",
    "Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil.",
    "Department of Engineering of Materials and Bioprocesses, School of Chemical Engineering, University of Campinas, P.O. Box 6066, Campinas 13083-852, SP, Brazil.",
    "Medical School, Tiradentes University Center, Maceió 57038-000, AL, Brazil.",
    "Department of Orthopedics and Traumatology, Federal University of Tocantins (UFT), Palmas 77001-090, TO, Brazil.",
    "Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil.",
    "Clinical Research, Anna Vitória Lana Institute (IAVL), Indaiatuba 13334-170, SP, Brazil.",
    "Medical School, Jaguariúna University Center (UniFAJ), Jaguariúna 13911-094, SP, Brazil."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Fábio Ramos Costa",
      "orcid": "0009-0003-0486-8114"
    },
    {
      "affs": [
        3
      ],
      "name": "Maria Helena Andrade Santana"
    },
    {
      "affs": [
        4
      ],
      "name": "Rubens Martins de Andrade",
      "orcid": "0000-0002-2513-9864"
    },
    {
      "affs": [
        5
      ],
      "name": "João Protásio Netto",
      "orcid": "0009-0005-3138-2886"
    },
    {
      "affs": [
        1
      ],
      "name": "Luyddy Pires",
      "orcid": "0009-0007-0725-7940"
    },
    {
      "affs": [
        2
      ],
      "name": "Gabriel Azzini",
      "orcid": "0000-0003-2884-7580"
    },
    {
      "affs": [
        2
      ],
      "name": "André Kruel",
      "orcid": "0000-0002-7415-3953"
    },
    {
      "affs": [
        2
      ],
      "name": "Tomas Mosaner"
    },
    {
      "affs": [
        2
      ],
      "name": "Lucas Furtado da Fonseca",
      "orcid": "0000-0001-6497-833X"
    },
    {
      "affs": [
        1,
        2,
        6,
        7,
        8
      ],
      "name": "José Fábio Lana"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/djc88k9e983he.bib",
  "cited_by": 0,
  "doi": "10.3390/gels12100867",
  "fulltext_url": "https://europepmc.org/articles/PMC13703993",
  "id": "djc88k9e983he",
  "issns": [
    "2310-2861"
  ],
  "landing_url": "https://europepmc.org/article/MED/42929902",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1313|Hydrogels: synthesis, properties, applications"
    ]
  ],
  "openalex": "W7214317646",
  "pdf_url": "https://europepmc.org/articles/PMC13703993?pdf=render",
  "pmcid": "PMC13703993",
  "pmid": "42929902",
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/djc88k9e983he.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42929902",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42929902"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1313|Hydrogels: synthesis, properties, applications",
      "subfield": "general"
    }
  ],
  "title": "Hyaluronan Hydrogels: Three Material States in Regenerative Orthopaedics.",
  "title_text": "Hyaluronan Hydrogels: Three Material States in Regenerative Orthopaedics.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/djc88k9e983he",
  "venue": "Gels (Basel, Switzerland)",
  "versions": []
}