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Vol. 16 (2024)

In Situ Deposition of Drug and Gene Nanoparticles on a Patterned Supramolecular Hydrogel to Construct a Directionally Osteochondral Plug

https://doi.org/10.1007/s40820-023-01228-w
Jiawei Kang
Department of Orthopaedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City 310009, Zhejiang Province, People’s Republic of China
Yaping Li
College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, People’s Republic of China
Yating Qin
College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, People’s Republic of China
Zhongming Huang
The Affiliated Nanhua Hospital, Orthopedic Research Centre, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, People’s Republic of China
Yifan Wu
Department of Orthopaedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City 310009, Zhejiang Province, People’s Republic of China
Long Sun
Department of Radiology, Jining No. 1 People’s Hospital, Jining Medical University, Jining 272000, Shandong, People’s Republic of China
Cong Wang
Department of Orthopaedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City 310009, Zhejiang Province, People’s Republic of China
Wei Wang
College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, People’s Republic of China
Gang Feng
Department of Orthopaedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City 310009, Zhejiang Province, People’s Republic of China
Yiying Qi
Department of Orthopaedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City 310009, Zhejiang Province, People’s Republic of China

Corresponding Author: Yiying Qi

qiyiying@zju.edu.cn

Nano-Micro Letters, Vol. 16 (2024), Article Number: 18

Abstract

The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone. Constructing multifactorial, spatially oriented scaffolds to stimulate osteochondral regeneration, has immense significance. Herein, targeted drugs, namely kartogenin@polydopamine (KGN@PDA) nanoparticles for cartilage repair and miRNA@calcium phosphate (miRNA@CaP) NPs for bone regeneration, were in situ deposited on a patterned supramolecular-assembled 2-ureido-4 [lH]-pyrimidinone (UPy) modified gelation hydrogel film, facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands. This hydrogel film can be rolled into a cylindrical plug, mimicking the Haversian canal structure of natural bone. The resultant hydrogel demonstrates stable mechanical properties, a self-healing ability, a high capability for reactive oxygen species capture, and controlled release of KGN and miR-26a. In vitro, KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways, respectively. In vivo, the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration, evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones, along with the successful integration of neocartilage with subchondral bone. This biomaterial delivery approach represents a significant toward improved osteochondral repair.


Highlights:
1 A multifactorial and oriented scaffolds was constructed to stimulate osteochondral regeneration.
2 This is the first demonstration that both drug and gene nanoparticles were spatially deposited on a patterned film through metal-ligand interactions.
3 For the first time, film-rolling approach was employed to construct osteochondral plug to mimick the Haversian canal structure of natural bone.

Keywords

Osteochondral regeneration Oriented hydrogel Kartogenin miRNA-26a
Kang, Jiawei, Yaping Li, Yating Qin, Zhongming Huang, Yifan Wu, Long Sun, Cong Wang, Wei Wang, Gang Feng, and Yiying Qi. 2023. “In Situ Deposition of Drug and Gene Nanoparticles on a Patterned Supramolecular Hydrogel to Construct a Directionally Osteochondral Plug”. Nano-Micro Letters 16 (November):18. https://doi.org/10.1007/s40820-023-01228-w.
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