Smart μ-Fiber Hydrogels with Macro-Porous Structure for Sequentially Promoting Multiple Phases of Articular Cartilage Regeneration

被引:37
作者
Ma, Zhijie [1 ]
Song, Wei [2 ]
He, Dan [1 ]
Zhang, Xin [1 ]
He, Yaohua [2 ,3 ]
Li, Haiyan [1 ,4 ]
机构
[1] Shanghai Jiao Tong Univ, Dept Orthoped, Affiliated Peoples Hosp 6, Sch Biomed Engn, 600 Yishan Rd, Shanghai 200233, Peoples R China
[2] Shanghai Jiao Tong Univ, Dept Orthoped, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China
[3] Shanghai Sixth Peoples Hosp, Jinshan Branch, Dept Orthoped, 147 Jiankang Rd, Shanghai 201599, Peoples R China
[4] RMIT Univ, Chem & Environm Engn, Sch Engn, 124 La Trobe St, Melbourne, Vic 3000, Australia
基金
中国国家自然科学基金;
关键词
cartilage regeneration; exosomes; macro-porous hydrogels; sequential delivery; MESENCHYMAL STEM-CELLS; HYALURONIC-ACID; DEGRADATION RATE; TISSUE; SCAFFOLDS; BONE; REPAIR; OSTEOARTHRITIS; PROLIFERATION; INFLAMMATION;
D O I
10.1002/adfm.202113380
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Hydrogels are widely utilized for articular cartilage regeneration. However, traditional hydrogels with nano-sized pores lead to poor cell and tissue infiltration. Furthermore, hydrogels that can stimulate each phase of cartilage regeneration to enhance cartilage repair are highly demanded. Herein, a macro-porous hydrogel is fabricated by crosslinking mixed sodium alginate (SA) and hyaluronic acid (HA) solution into SA/HA micro-fibers (mu-fibers) first and subsequently crosslinking the mu-fibers into hydrogel blocks. Besides, exosomes derived from NR8383 cells activated by lipopolysaccharides (LPS) and stimulated with bioglass (BG) ion extracts (LPS/BG-exo) are incorporated into the hydrogel as they exhibit a strong ability to regulate inflammation homeostasis and recruit bone marrow mesenchymal stem cells (BMMSCs). Meanwhile, poly (lactic-co-glycolic acid) (PLGA) microspheres containing kartogenin (KGN) (PLGA(KGN)) are encapsulated within the hydrogel for inducing the chondrogenic differentiation of recruited BMMSCs when KGN is released after the LPS/BG-exo. Thus, the obtained macro-porous SA/HA(exo)-PLGA(KGN) hydrogel can not only significantly improve the infiltration of tissues into the hydrogel but also sequentially deliver LPS/BG-exo and KGN to enhance the cartilage regeneration in a rat cartilage defect model. Prospectively speaking, the SA/HA(exo)-PLGA(KGN) hydrogel is a potential candidate for other tissue regeneration as the bioactive substances can be adjusted according to different purposes.
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页数:20
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