摘要
Cartilage tissue engineering is a promising strategy for repairing cartilage defects.However,achieving satisfactory cartilage regeneration in vitro and maintaining its stability in vivo remains a challenge.The key to achieving this goal is establishing an efficient cartilage regeneration culture system to retain sufficient active cells with physiological functions,generate abundant cartilage extracellular matrix(ECM)and maintain a low level of cartilage ECM degradation.The current chondrogenic medium(CM)can effectively promote cartilage ECM production;however,it has a negative effect on cell proliferation.Meanwhile,the specific c-Jun N-terminal kinase pathway inhibitor SP600125 promotes chondrocyte proliferation but inhibits ECM synthesis.Here,we aimed to construct a three-dimensional cartilage regeneration model using a polyglycolic acid/polylactic acid scaffold in combination with chondrocytes to investigate the effect of different culture modes with CM and SP600125 on in vitro cartilage regeneration and their long-term outcomes in vivo systematically.Our results demonstrate that the long-term combination of CM and SP600125 made up for each other and maximized their respective advantages to obtain optimal cartilage regeneration in vitro.Moreover,the long-term combination achieved stable cartilage regeneration after implantation in vivo with a relatively low initial cell-seeding concentration.Therefore,the long-term combination of CM and SP600125 enhanced in vitro and in vivo cartilage regeneration stability with fewer initial seeding cells and thus optimized the cartilage regeneration culture system.
基金
supported by the National Key Research and Development Program of China(2017YFC1103900 and 2018YFC1105800)
the National Natural Science Foundation of China(81871502 and 81701843)
the Program of Shanghai Academic/Technology Research Leader(19XD1431100)
the Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(2019CXJQ01)
the Clinical Research Plan of SHDC(No.SHDC2020CR2045B),Shanghai Municipal Key Clinical Specialty(shslczdzk06601)
Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiao Tong University School of Medicine(2022LHA07).
作者简介
Peiling Zhang,These authors contributed equally to this work and share the first authorship;Qianyi Wang,These authors contributed equally to this work and share the first authorship;Jie Chen,These authors contributed equally to this work and share the first authorship;Correspondence address:Xiaoyun Wang.E-mail:gaokongliuyun@126.com;Correspondence address:Guangdong Zhou,guangdongzhou@126.com。
