Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration

被引：441

作者：

Chen, Pengfei ^{[1
,2
]}

Zheng, Lin ^{[1
,2
,3
]}

Wang, Yiyun ^{[1
,2
]}

Tao, Min ^{[1
,2
]}

Xie, Ziang ^{[1
,2
]}

Xia, Chen ^{[1
,2
]}

Gu, Chenhui ^{[1
,2
]}

Chen, Jiaxin ^{[1
,2
]}

Qiu, Pengcheng ^{[1
,2
]}

Mei, Sheng ^{[1
,2
]}

Ning, Lei ^{[1
,2
]}

Shi, Yiling ^{[1
,2
]}

Fang, Chen ^{[1
,2
]}

Fan, Shunwu ^{[1
,2
]}

Lin, Xianfeng ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Orthopaed Surg, Med Coll, Hangzhou, Zhejiang, Peoples R China

[2] Key Lab Musculoskeletal Syst Degenerat & Regenera, Hangzhou, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Affiliated Hosp 5, Lishui Municipal Cent Hosp, Dept Orthoped, Lishui, Peoples R China

来源：

THERANOSTICS | 2019年 / 9卷 / 09期

基金：

国家重点研发计划;

关键词：

3D printing; cartilage extracellular matrix; exosome; osteochondral defect; ARTICULAR-CARTILAGE; COLLAGEN SCAFFOLD; IN-VITRO; MATRIX; REPAIR; HYDROGEL; OSTEOARTHRITIS; MICROSPHERES; PATHOGENESIS; ORIENTATION;

D O I：

10.7150/thno.31017

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods: We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro. We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results: The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion: This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.

引用

页码：2439 / 2459

页数：21

共 53 条

[21]

A Difunctional Regeneration Scaffold for Knee Repair based on Aptamer-Directed Cell Recruitment [J].