2. Academic Validation
  3. Carnosine-modified gelatin-hyaluronic acid hydrogel comprising fenofibrate-loaded nanoparticles targeting chondrocyte ferroptosis and macrophage polarization for synergistic osteoarthritis therapy

Carnosine-modified gelatin-hyaluronic acid hydrogel comprising fenofibrate-loaded nanoparticles targeting chondrocyte ferroptosis and macrophage polarization for synergistic osteoarthritis therapy

  • Int J Biol Macromol. 2026 Apr:354:151281. doi: 10.1016/j.ijbiomac.2026.151281.
Weibei Sheng 1,  Tianyou Guo 2,  Bo Yu 3,  Jin Zhao 1,  Cehui Hu 1,  Jianjing Lin 4,  Jian Weng 1,  Yingqi Chen 3,  Deli Wang 1,  Fei Yu 5,  Yan Hu 6,  Hui Zeng 7,  Peng Liu 8
Affiliations

Affiliations

  • 1 Department of Bone & Joint Surgery, Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
  • 2 Department of Bone & Joint Surgery, Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, 518036, China; Anhui Medical University, China.
  • 3 Department of Orthopedic Trauma, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
  • 4 Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, 518035, China.
  • 5 Department of Spine Surgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China. Electronic address: [email protected].
  • 6 Obstetrics and Gynecology Center of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen, 518035, China. Electronic address: [email protected].
  • 7 Department of Bone & Joint Surgery, Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, 518036, China; Department of Orthopedic Trauma, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China. Electronic address: [email protected].
  • 8 Department of Bone & Joint Surgery, Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, 518036, China. Electronic address: [email protected].
PMID: 41812949 DOI: 10.1016/j.ijbiomac.2026.151281
Abstract

Osteoarthritis (OA), a debilitating and progressive joint disease, presents major therapeutic challenges due to chondrocyte Ferroptosis, chronic synovial inflammation, and the pharmacokinetic limitations of conventional intra-articular therapies, such as rapid clearance and poor retention. To overcome these barriers, we developed a dual-functional intra-articular delivery platform composed of a gelatin-hyaluronic acid hydrogel encapsulating fenofibrate-loaded, cartilage-targeting nanoparticles (FNPs-GelHA hydrogel). This system synergistically inhibits OA progression by simultaneously suppressing chondrocyte Ferroptosis and modulating the inflammatory joint microenvironment. In vitro studies revealed that FNPs-GelHA hydrogel markedly attenuates chondrocyte Ferroptosis, inflammation, oxidative stress, and lipid peroxidation. Furthermore, this system effectively reprograms macrophage polarization by suppressing pro-inflammatory M1 phenotypes and promoting reparative M2 phenotypes, thereby contributing to immunomodulation and cartilage repair. In addition, in vivo experiments demonstrated prolonged joint retention of this system and significant therapeutic efficacy in delaying OA progression. By integrating targeted drug delivery, Ferroptosis inhibition, and immune microenvironment remodeling, this composite hydrogel-nanoparticle platform offers a synergistic and promising strategy for OA treatment.

Keywords

Fenofibrate; Ferroptosis; Gelatin–hyaluronic acid hydrogel; Macrophage polarization; Osteoarthritis; Targeted nanoparticles.

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