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

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

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: weich_doctor@163.com.
  • 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: yichen_doctor@163.com.
  • 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: yzgad@163.com.
  • 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: doctorguo_301@163.com.
  • 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: clear_ann@163.com.
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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