2. Academic Validation
  3. Injectable immunomodulation-based porous chitosan microspheres/HPCH hydrogel composites as a controlled drug delivery system for osteochondral regeneration

Injectable immunomodulation-based porous chitosan microspheres/HPCH hydrogel composites as a controlled drug delivery system for osteochondral regeneration

  • Biomaterials. 2022 Jun;285:121530. doi: 10.1016/j.biomaterials.2022.121530.
Xiongfa Ji 1,  Hongwei Shao 2,  Xiaohong Li 3,  Muhammad Wajid Ullah 4,  Guowen Luo 2,  Ziyang Xu 2,  Limin Ma 5,  Xuecheng He 5,  Zehua Lei 5,  Qian Li 2,  Xulin Jiang 6,  Guang Yang 7,  Yu Zhang 8
Affiliations

Affiliations

  • 1 Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China. Electronic address: [email protected].
  • 2 Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; School of Medicine, South China University of Technology, Guangzhou, 510006, China.
  • 3 State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.
  • 4 Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China; Biofuels Institute, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, 212013, China.
  • 5 Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
  • 6 Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, China. Electronic address: [email protected].
  • 7 Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. Electronic address: [email protected].
  • 8 Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; School of Medicine, South China University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
PMID: 35504181 DOI: 10.1016/j.biomaterials.2022.121530
Abstract

The inappropriate regenerated fibrous cartilage and subchondral bone of the injured chondral defect ultimately cause degeneration of the regenerated cartilage, which eventually leads to the failure of cartilage repair. In this study, we developed a macrophage-modulated and injectable 'building block' drug delivery system comprised of porous chitosan (CS) microspheres and hydroxypropyl chitin (HPCH) hydrogel, where the dimethyloxallyl glycine (DMOG) was encapsulated in the thermosensitive HPCH hydrogel (HD) while kartogenin (KGN) was conjugated on the porous CS microspheres (CSK-PMS). The developed HD/CSK-PMS composite scaffold effectively modulated the microenvironment at the defect site, achieved local macrophage M2 polarization and promoted cartilage regeneration. The fast-degradable HD favored hyaline cartilage regeneration, while the highly stable CSK-PMS supported the endochondral ossification and regenerated the subchondral bone. In vitro and in vivo evaluations revealed that the newly developed HD/CSK-PMS as a controlled drug delivery system could effectively create M2 macrophage microenvironment and orchestrate osteochondral (OC) regeneration. These findings indicate the importance of the immune microenvironment and subchondral bone for high-quality cartilage repair, and thus the immunomodulation-based hydrogel/PMS composite system could be a promising candidate for OC regeneration.

Keywords

Drug delivery system; Hydrogel; Immunomodulation; Osteochondral regeneration; Porous microsphere.

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