Metallic Scaffold with Micron-Scale Geometrical Cues Promotes Osteogenesis and Angiogenesis via the ROCK/Myosin/YAP Pathway

Liu, Yang1; Yang, Qihao2; Wang, Yue3; Lin, Minmin1; Tong, Yanrong1; Huang, Hanwei1; Yang, Chengyu1; Wu, Jianqun4; Tang, Bin1; Bai, Jiaming3; Liu, Chao1

2022-07-01

10.1021/acsbiomaterials.2c00225

ACS Biomaterials Science & Engineering   Impact Factor & Quartile

2373-9878

The advent of precision manufacturing has enabled the creation of pores in metallic scaffolds with feature size in the range of single microns. In orthopedic implants, pore geometries at the micron scale could regulate bone formation by stimulating osteogenic differentiation and the coupling of osteogenesis and angiogenesis. However, the biological response to pore geometry at the cellular level is not clear. As cells are sensitive to curvature of the pore boundary, this study aimed to investigate osteogenesis inhigh- vs low-curvature environments by utilizing computer numerical control laser cutting to generate triangular and circular precision manufactured micropores (PMpores). We fabricated PMpores on 100 mu m-thick stainless-steel discs. Triangular PMpores had a 30 degrees vertex angle and a 300 mu m base, and circular PMpores had a 300 mu m diameter. We found triangular PMpores significantly enhanced the elastic modulus, proliferation, migration, and osteogenic differentiation of MC3T3-E1 preosteoblasts through Yes-associated protein (YAP) nuclear translocation. Inhibition of Rho-associated kinase (ROCK) and Myosin II abolished YAP translocation in all pore types and controls. Inhibition of YAP transcriptional activity reduced the proliferation, pore closure, collagen secretion, alkaline phosphatase (ALP), and Alizarin Red staining in MC3T3-E1 cultures. In C166 vascular endothelial cells, PMpores increased the VEGFA mRNA expression even without an angiogenic differentiation medium and induced tubule formation and maintenance. In terms of osteogenesis-angiogenesis coupling, a conditioned medium from MC3T3-E1 cells in PMpores promoted the expression of angiogenic genes in C166 cells. A coculture with MC3T3-E1 induced tubule formation and maintenance in C166 cells and tubule alignment along the edges of pores.Together, curvature cues in micropores are important stimuli to regulate osteogenic differentiation and osteogenesis-angiogenesis coupling. This study uncovered key mechanotransduction signaling components activated by curvature differences in a metallic scaffold and contributed to the understanding of the interaction between orthopedic implants and cells.

bone tissue engineering precision laser cutting pore geometry osteogenic differentiation angiogenesis

SCI ; EI

English

First ; Corresponding

Shenzhen Science and Technology Innovation Commission["JCYJ20190809114209434","KQTD20200820113012029"] ; Guangdong Provincial Key Laboratory of Advanced Biomaterials[2022B1212010003]

Materials Science

Materials Science, Biomaterials

WOS:000830010600001

AMER CHEMICAL SOC

20223312565518

Computer control systems ; Endothelial cells ; Geometry ; Laser beams ; Phosphatases ; Scaffolds (biology)

Biomedical Engineering:461.1 ; Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Computer Applications:723.5 ; Control Systems:731.1 ; Laser Beam Interactions:744.8 ; Chemical Products Generally:804 ; Mathematics:921

Web of Science

1.Southern Univ Sci & Technol, Coll Engn, Dept Biomed Engn, Guangdong Prov Key Lab Adv Biomat, Shenzhen 518055, Peoples R China
2.Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou 510150, Peoples R China
3.Southern Univ Sci & Technol, Coll Engn, Dept Mech & Energy Engn, Shenzhen 518055, Peoples R China
4.Southern Univ Sci & Technol, Coll Med, Shenzhen 518055, Peoples R China

Liu, Yang,Yang, Qihao,Wang, Yue,et al. Metallic Scaffold with Micron-Scale Geometrical Cues Promotes Osteogenesis and Angiogenesis via the ROCK/Myosin/YAP Pathway[J]. ACS Biomaterials Science & Engineering,2022,8(8):3498-3514.

Liu, Yang.,Yang, Qihao.,Wang, Yue.,Lin, Minmin.,Tong, Yanrong.,...&Liu, Chao.(2022).Metallic Scaffold with Micron-Scale Geometrical Cues Promotes Osteogenesis and Angiogenesis via the ROCK/Myosin/YAP Pathway.ACS Biomaterials Science & Engineering,8(8),3498-3514.

Liu, Yang,et al."Metallic Scaffold with Micron-Scale Geometrical Cues Promotes Osteogenesis and Angiogenesis via the ROCK/Myosin/YAP Pathway".ACS Biomaterials Science & Engineering 8.8(2022):3498-3514.