{
  "abstract": "Microcurrent stimulation has emerged as a promising biophysical cue for cartilage regeneration, but its dose-dependent effects in 3-dimensional engineered cartilage constructs remain unclear. Here, we investigated the effects of continuous direct microcurrent stimulation on auricular chondrocytes and engineered cartilage spheroids using 0-, 10-, 25-, 50-, 100-, and 200-μA stimulation for 30 min daily. In 2-dimensional culture, microcurrent stimulation did not markedly increase the DNA content or Cell Counting Kit-8 value, indicating that it did not markedly promote cell expansion or overall metabolic activity. 5-Ethynyl-2'-deoxyuridine and Ki67 assays showed that low to moderate (<50 μA) stimulation had limited effects on proliferation, whereas 100 to 200 μA attenuated proliferative activity. Nevertheless, microcurrent stimulation enhanced chondrogenic marker expression in a biphasic manner, with type II collagen, SRY-box transcription factor 9, aggrecan, and cartilage oligomeric matrix protein increasing from 0 to 50 μA and declining from 50 to 200 μA. In 3-dimensional spheroids, 50 μA produced the most favorable morphology, cartilage-specific extracellular matrix deposition, mechanical properties, and hyaline cartilage-like phenotype. Excessive stimulation increased catabolic, inflammatory, and apoptosis-associated molecular responses without causing obvious cytotoxicity, apoptosis, reactive oxygen species production, temperature change, or pH alteration. Mechanistically, 50 μA induced coordinated Ca²⁺ signaling and promoted nuclear factor of activated T cells (NFAT) nuclear translocation, whereas 200 μA generated dysregulated Ca²⁺ responses and inefficient NFAT activation. Verapamil, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, and cyclosporin A attenuated 50-μA-induced NFAT activation, supporting the involvement of the Ca²⁺/calcineurin/NFAT pathway. Furthermore, 50-μA-preconditioned spheroids showed superior cartilage-forming capacity after subcutaneous implantation. These findings identify 50 μA as a favorable bioelectrical stimulation condition within the tested intensity range and provide a practical strategy for enhancing cartilage spheroid maturation in cartilage tissue engineering.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yong Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Siqiang Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiangsheng Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Bo Tao",
      "orcid": "0009-0008-8569-2953"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fdd0qbt56akje.bib",
  "cited_by": 0,
  "doi": "10.34133/research.1462",
  "fulltext_url": "https://europepmc.org/articles/PMC13678085",
  "id": "fdd0qbt56akje",
  "issns": [
    "2639-5274"
  ],
  "landing_url": "https://europepmc.org/article/MED/42898673",
  "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",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
  ],
  "openalex": "W7216118685",
  "pdf_url": "https://europepmc.org/articles/PMC13678085?pdf=render",
  "pmcid": "PMC13678085",
  "pmid": "42898673",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fdd0qbt56akje.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42898673",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898673"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "Effect of Microcurrent Stimulation on Cartilage Regeneration in Engineered Chondrocyte Spheroids.",
  "title_text": "Effect of Microcurrent Stimulation on Cartilage Regeneration in Engineered Chondrocyte Spheroids.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/fdd0qbt56akje",
  "venue": "Research (Washington, D.C.)",
  "versions": []
}