Precision 3D printed meniscus scaffolds to facilitate hMSCs proliferation and chondrogenic differentiation for tissue regeneration

Journal of Nanobiotechnology

Fangqian Wang¹  Yikai Wang¹  Xiaohua Yu²  Fang Geng³  Xin Tang³  Wei Zhang³  Zhenzhen Li⁴  Xingyu Deng⁴  Jie Zhang⁴  Xiabin Chen⁴  Shurong Hou⁴  Na Zheng⁵  Peng Wang⁶ 

[1] Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, 310009, Hangzhou, China;Zhejiang Provincial Key Laboratory of Orthopaedics, Hangzhou, Zhejiang Province, China;Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, 310009, Hangzhou, China;Zhejiang Provincial Key Laboratory of Orthopaedics, Hangzhou, Zhejiang Province, China;Orthopedics Research Institute of Zhejiang University, 310009, Hangzhou, Zhejiang Province, China;Medtronic Technology Center, 201114, Shanghai, China;School of Pharmacy, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, China;State Key Laboratory of Chemical Engineering, School of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, China;The State Key Laboratory of Translational Medicine and Innovative Drug Development, 210042, Nanjing, China;

关键词: Meniscus;    Tissue engineering;    Scaffold;    Chondrogenic differentiation;   

DOI  :  10.1186/s12951-021-01141-7

来源: Springer

【 摘 要 】

BackgroundThe poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue.ResultsHerein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility.ConclusionsOverall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration.Graphical Abstract

【 授权许可】

CC BY