吉林大学学报(医学版) ›› 2021, Vol. 47 ›› Issue (2): 519-527.doi: 10.13481/j.1671-587X.20210235
张诗晨1,2,金丽鸥1,李跃1,郑晓雪1,2,王婧1,2,魏欣1,2,王众泽1,2,韩冰1()
收稿日期:
2020-05-03
出版日期:
2021-03-28
发布日期:
2021-03-25
通讯作者:
韩冰
E-mail:hbing@jlu.edu.cn
作者简介:
张诗晨(1993-),女,吉林省通化市人,在读硕士研究生,主要从事口腔颌面外科方面的研究。
基金资助:
Received:
2020-05-03
Online:
2021-03-28
Published:
2021-03-25
摘要:
kartogenin (KGN) 是近年来发现的小分子物质,其可通过调节核心结合因子β亚基(CBFβ)-Runt相关转录因子1(RUNX1)等信号通路促进间充质干细胞(MSCs)增殖和成软骨分化修复软骨缺损,并可与转化生长因子β3(TGF-β3)产生协同作用。KGN的成软骨分化作用还与其旁分泌机制有关。除促软骨再生修复外,KGN还可通过保护软骨和软骨细胞,促进人润滑素分泌,保护和改建软骨下骨及缓解疼痛,从而对骨关节炎(OA)产生治疗作用。此外,利用KGN的结构和功能特点,大量软骨组织工程学研究将其以物理或化学方法结合于各类载体以修复软骨缺损和治疗OA。现结合相关文献阐述KGN对OA的治疗作用机制,并从纳米级和微米级聚合物、水凝胶及其他聚合物支架三3方面就软骨组织工程学研究中用以搭载KGN的载体组成、理化特点、释药特点及优势性能等进行综述,旨在为OA的软骨组织工程学治疗提供新思路和新靶点。
中图分类号:
张诗晨,金丽鸥,李跃,郑晓雪,王婧,魏欣,王众泽,韩冰. kartogenin对骨关节炎的治疗作用机制及其在软骨组织工程学中应用的研究进展[J]. 吉林大学学报(医学版), 2021, 47(2): 519-527.
表1
搭载KGN的纳米载体及主要特点"
Composition | Size by DLS(l/nm) | Surface charge | Carrying method and loading rate | KGN release characteristic | Scaffold | Advantage and feature |
---|---|---|---|---|---|---|
RGD-KGN- UCNP@SiO2 NPs | 35 | n/a | Conjugated; n/a | More than 50% in 4 h with NIR irradiation | n/a | Long-term tracking of hMSCs by using NIR light; NIR-triggered release of KGN in hMSCs |
PN-KGN NPs | 25 | + | Conjugated; n/a | 20% in 30 d | n/a | Promoting electrostatic interactions with cartilage matrix; protecting cartilage for more than 12 weeks after IA injection |
PN-KGN NPs | 25 | + | Conjugated; 13% | 11% in 11 d | AMSA/AG hydrogels | Recruiting endogenous MSCs; synergistically enhancing the chondrogenesis of MSCs by loading both KGN and TGF-β3 |
USPIO-KGN NPs | 14±3 | n/a | Conjugated; n/a | 32% in 6 d | Collagen /cellulose nanocrystals scaffold | Recruiting endogenous MSCs;noninvasively monitoring the sca?olds degradation process and observing the neocartilage regeneration by MRI |
USPIO-KGN NPs | 14±2(TEM) | n/a | Conjugated; n/a | 32% in 6 d | Cellulose nanocrystal/ dextran hydrogels | Recruiting endogenous MSCs; noninvasively monitoring the degradation of hydrogels and neocartilage regeneration in realtime by MRI |
F127/COS/ KGNDCF nanospheres | 4 ℃:650; 37 ℃:305 | n/a | Conjugated; n/a | 20%—50% in 14 d (enhanced with decreasing F127 content ) | n/a | Rapid release of DCF for subsidence of inflammation, sustained release of KGN for cartilage regeneration; release enhanced by cold treatment |
PGS-KGN nanofibers | 617±235(SEM) | n/a | Loaded; n/a | (0.32±0.03) μg·mg-1(weight of scaffold) in 21 d | PGS/PCL aligned nanofibers | Mimicking structural features of ECM in superficial zone of articular cartilage |
HNT/KGN | 0.002wt% HNT:235±20;0.005wt% HNT: 219±13 | — | Loaded; 6wt% | In PBS:70% in 7 d; In synovial fluid: 100% in 38 d; Hydrogels in PBS:more than 50% in 25 h | HNT/ KGN/ Lap hydrogels | HNT reinforced the rheological properties of the hydrogel;self-repairing after disruption; stable to ultrasound irradiation |
PLGA-KGN NPs | 270 | n/a | Loaded; 7.5wt% | Free : 85% in 60 d; In hydrogels: 70% in 60 d | Acylated HA hydrogels | Recruiting endogenous MSCs;in situ gelation under UV light;sustained release manner |
CHI-KGN NPs/ CHI-KGN MPs | NPs: 150±39; MPs: 1840±540 | —/+ | Conjugated; NPs:(98.1±1.6)%;MPs:(97.9±1.9)% | NPs: 30% in 50 d; MPs: 50% in 50 d | n/a | Sustained release profiles; greater ability for NPs to promote chondrogenic differentiation and cartilage regeneration |
PEG-PAMAM- KGN(PPK)/KGN-PEG- PAMAM(KPP) | PPK:36.2±0.2; KPP:33.3±0.4 | —/+ | Conjugated; PPK:(5.50± 0.2)wt%; KPP:(5.23±0.34)wt% | n/a | n/a | Positive surface charge promoting cellular uptake |
PEG-KGN micelles/ HA-PEG-KGN hydrogels | Free: 341.4±58.5;HA hydrogels: 424.7±102.3 | n/a | Conjugated; n/a | Micelles:(51.2±5.7)% in 48 h; Hydrogels:(32.4±3.3)% in 5 d | HA hydrogels | Synergistically acting with HA to inhibit the progress of OA |
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