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Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
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Coupling Mitochondrial Homeostasis to Oxi-Inflamm-Aging Network Disruption via Peptide-Functionalized Nanocomposite

Zhao Zhang1, Xiaohe Wang1, Pengyu Fan2

  • 1Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

Advanced Materials (Deerfield Beach, Fla.)
|December 26, 2025
PubMed

Insights

A novel nanocomposite hydrogel targets osteoarthritis by disrupting oxidation, inflammation, and aging. This mitochondria-centered therapy protects chondrocytes and alleviates joint damage in a rat model.

Area of Science:

  • Biomaterials Science
  • Nanomedicine
  • Osteoarthritis Research

Background:

  • Osteoarthritis (OA) is a major global health burden driven by the interplay of oxidation, inflammation, and aging (oxi-inflamm-aging), disrupting chondrocyte homeostasis.
  • Current OA therapies lack clinical efficacy, necessitating innovative treatment strategies.

Purpose of the Study:

  • To develop a mitochondria-centered therapeutic strategy to disrupt the pathogenic oxi-inflamm-aging network in OA.
  • To engineer a peptide-functionalized nanocomposite hydrogel for enhanced OA treatment.

Main Methods:

  • A novel chimeric peptide (MW) integrating mitochondrial protection (MOTS-s) and cartilage targeting (WYRGRL) was synthesized.
  • The MW peptide was immobilized onto GeSe nanosheets and embedded in a responsive hydrogel (HMP) to form MW@GeSe@HMP.
  • In vitro and in vivo OA models were used to evaluate the hydrogel's efficacy in scavenging radicals, targeted release, chondrocyte protection, and OA alleviation.

Main Results:

  • The MW@GeSe@HMP hydrogel demonstrated enzyme-mimicking properties for radical scavenging and MMP-responsive release in chondrocytes.
  • The hydrogel effectively disrupted the oxi-inflamm-aging network, modulated mitochondrial function, and maintained chondrocyte homeostasis.
  • MW@GeSe@HMP protected chondrocytes by inhibiting cGAS/STING signaling, suppressed cartilage damage, and alleviated OA progression in a rat model.

Conclusions:

  • A peptide-functionalized nanocomposite hydrogel (MW@GeSe@HMP) was successfully developed for OA treatment.
  • This strategy offers a prospective therapeutic approach by regulating the oxi-inflamm-aging network and targeting mitochondrial dysfunction.
  • The study highlights a potential new therapeutic target for OA by addressing the integrated pathological pathways.
Keywords:
chimeric peptide: 2D GeSehydrogelosteoarthritisoxi‐inflamm‐aging

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