2. Academic Validation
  3. An injectable self-lubricating supramolecular polymer hydrogel loaded with platelet lysate to boost osteoarthritis treatment

An injectable self-lubricating supramolecular polymer hydrogel loaded with platelet lysate to boost osteoarthritis treatment

  • J Control Release. 2024 Oct 7:376:20-36. doi: 10.1016/j.jconrel.2024.09.052.
Peng Zhang 1,  Jianhai Yang 2,  Zhuoya Wang 2,  Hongying Wang 2,  Mingyang An 3,  Maihemuti Yakufu 4,  Wenliang Wang 5,  Yujie Liu 6,  Wenguang Liu 7,  Chunbao Li 8
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Department of Sports Medicine, Characteristic Medical Center of Chinese People's Armed Police Forces, Tianjin 300162, China.
  • 2 School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300350, China.
  • 3 Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China.
  • 4 Department of Orthopedic Research Center, Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi 830002, China.
  • 5 Department of Sports Medicine, Characteristic Medical Center of Chinese People's Armed Police Forces, Tianjin 300162, China.
  • 6 Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China. Electronic address: liuyujie301@163.com.
  • 7 School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300350, China. Electronic address: wgliu@tju.edu.cn.
  • 8 Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China. Electronic address: lichunbao301@163.com.
PMID: 39362609 DOI: 10.1016/j.jconrel.2024.09.052
Abstract

Globally, osteoarthritis (OA) is the most prevalent joint disease and is characterized by infiltration of M1 macrophages in the synovium, anabolic-catabolic imbalance of the extracellular matrix (ECM), increased articular shear force and overproduction of Reactive Oxygen Species (ROS). Disease-modifying OA drugs are not yet available, and treatments for OA focus solely on reducing pain and inflammation and have limited therapeutic effect. Herein, we developed an injectable self-lubricating poly(N-acryloyl alaninamide) (PNAAA) hydrogel loaded with platelet lysate (PL) (termed "PNAAA@PL") for treating OA. Tribological and drug release tests revealed suitable lubrication properties and sustained release of bioactive factors in PNAAA@PL. In vitro experiments showed that PNAAA@PL alleviated interleukin-1β (IL-1β)-induced anabolic-catabolic imbalance of chondrocytes and repolarized pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype via intracellular ROS scavenging. Additionally, the PNAAA@PL hydrogel enhanced the migratory capacity and chemotaxis ability of stem cells, which are essential for chondrogenesis. In vivo, the functionalized PNAAA@PL hydrogel acted like synovial fluid following intra-articular injection into a rat OA model with anterior cruciate ligament transection, ultimately attenuating cartilage degeneration and synovitis. According to molecular mechanism studies, PNAAA@PL repairs cartilage in the OA model by inhibiting the NF-ĸB pathway. Overall, this self-lubricating PNAAA@PL hydrogel offers a comprehensive strategy for preventing OA progression by engineering a biophysiochemical microenvironment to generate high-quality hyaline cartilage.

Keywords

Osteoarthritis; Platelet lysate; Reactive oxygen species; Self-lubricating; Supramolecular polymer hydrogels.

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