Lipid nanoparticle-assisted miR29a delivery based on core-shell nanofibers improves tendon healing by cross-regulation of the immune response and matrix remodeling

  • Biomaterials. 2022 Nov 12;291:121888. doi: 10.1016/j.biomaterials.2022.121888.
Wei Chen  1 ,  Yi Chen  2 ,  Yiming Ren  3 ,  Cangjian Gao  3 ,  Chao Ning  4 ,  Haotian Deng  3 ,  Peiqi Li  3 ,  Yang Ma  4 ,  Hao Li  3 ,  Liwei Fu  3 ,  Guangzhao Tian  3 ,  Zhen Yang  3 ,  Xiang Sui  4 ,  Zhiguo Yuan  5 ,  Quanyi Guo  6 ,  Shuyun Liu  7
Affiliations
  • 1. Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No.28 Fuxing Road, Haidian District, Beijing, 100853, China; School of Medicine, Nankai University, Tianjin, 300071, China. Electronic address: [email protected].
  • 2. School of Medicine, Nankai University, Tianjin, 300071, China; Department of Plastic and Reconstructive Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: [email protected].
  • 3. Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No.28 Fuxing Road, Haidian District, Beijing, 100853, China; School of Medicine, Nankai University, Tianjin, 300071, China.
  • 4. Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No.28 Fuxing Road, Haidian District, Beijing, 100853, China.
  • 5. Department of Bone and Joint Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. Electronic address: [email protected].
  • 6. Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No.28 Fuxing Road, Haidian District, Beijing, 100853, China; School of Medicine, Nankai University, Tianjin, 300071, China. Electronic address: [email protected].
  • 7. Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No.28 Fuxing Road, Haidian District, Beijing, 100853, China; School of Medicine, Nankai University, Tianjin, 300071, China. Electronic address: [email protected].
PMID: 36403324 DOI: 10.1016/j.biomaterials.2022.121888
Abstract

Inferior healing and peritendinous adhesions are the major clinical problems following Achilles tendon injury, leading to impaired motor function and an increased risk of re-rupture. These complications are presumed to be inextricably linked to inflammation and fibroscar formation. Here, microRNA29a is identified as a promising therapeutic target for tendon injury through the cross-regulation of the immune response and matrix remodeling. MiR29a-LNPs were successfully prepared by microfluidic technology. They are then loaded into the core-shell nanofibers to achieve local delivery in the injured tendon, where the shell layer is composed of PELA for anti-adhesion. Our studies reveal that miR29a regulates Collagen synthesis and NF-κB activation in tenocytes, and promotes macrophage polarization by inhibiting the inflammasome pathway. In vivo studies of the Achilles tendon-rupture model indicate the best repair in the miR29a group, as evidenced by superior Collagen composition and alignment, higher mechanical strength, and better functional recovery. In conclusion, a functionalized anti-adhesive membrane that promotes nascent tendon matrix remodeling and improves the regenerative immune microenvironment is developed for the treatment of tendon injury.

Keywords
Coaxial electrospun; Immune regulation; Lipid nanoparticles; Matrix remodeling; MicroRNA-29a; Tendon.
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