Injectable hydrogel microspheres that enhance autophagy can improve cartilage microenvironment and resist chondrocyte senescence
- VernacularTitle:增强自噬的可注射水凝胶微球改善软骨微环境抗软骨细胞衰老
- Author:
Wenming LI
1
;
Yonghang LI
1
;
Caiping YAN
1
;
Xingkuan WANG
1
;
Chao XIANG
1
;
Yuan ZHANG
1
;
Ke JIANG
1
;
Lu CHEN
1
Author Information
- Publication Type:Journal Article
- Keywords: osteoarthritis; hydrogel microsphere; autophagy; senescent cell; senescence-associated secretory phenotype; rapamycin
- From: Chinese Journal of Tissue Engineering Research 2025;29(22):4710-4719
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Cell senescence is one of the major risk factors for osteoarthritis,but there is no widely accepted anti-osteoarthritis therapy targeting senescent cells.OBJECTIVE:To develop a feasible treatment strategy targeting senescent cells in osteoarthritis.METHODS:The cationic liposome containing rapamycin,RAPA@Lipo,was prepared by thin film dispersion method.Methylallylated hyaluronic acid hydrogel was synthesized,and RAPA@Lipo was added to the methylallylated hyaluronic acid hydrogel aqueous phase solution.The hydrogel microspheres were prepared by microfluidic equipment.Solid hydrogel microspheres(RAPA@Lipo@MS)were crosslinked under violet light.Primary human chondrocytes were co-cultured with RAPA@Lipo and RAPA@Lipo@MS,respectively.The biocompatibility of the materials was evaluated by CCK-8 assay and live/dead staining.Primary rat chondrocytes were cultured in four groups.Normal control group was cultured for 48 hours.The model group was stimulated with H2O2 for 24 hours to establish senescent cell model.RAPA@Lipo group and RAPA@Lipo@MS group were cultured for 24 hours after establishing senescent cell model with RAPA@Lipo and RAPA@Lipo@MS,respectively.After culture,immunofluorescence was used to observe the expression of p62 and type Ⅱ collagen.RT-PCR was used to detect the mRNA expression of interleukin 6,matrix metalloproteinase 13,type Ⅱ collagen,aggrecan,and ADAMTS-5.RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead staining showed that RAPA@Lipo and RAPA@Lipo@MS had good biocompatibility.(2)Compared with the normal control group,the protein expression of p62 was increased(P<0.05);the expression of type Ⅱ collagen was decreased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were increased(P<0.05);mRNA expression levels of type Ⅱ collagen and aggrecan were decreased(P<0.05)in the model group.Compared with the model group,the expression of p62 protein was decreased(P<0.05);the expression of type Ⅱ collagen was increased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were decreased(P<0.05);mRNA expression of type Ⅱ collagen and aggrecan increased(P<0.05)in the RAPA@Lipo@MS group.(3)These findings indicate that RAPA@Lipo@MS can control the quality of cells in vivo by enhancing autophagy,reduce senescent cells in vivo,and locally eliminate senescent cells and senescence-associated secretory phenotype factors in osteoarthritis,thereby slowing the progression of osteoarthritis and creating a cartilage microenvironment that promotes regeneration.
