Promoting in vivo early angiogenesis with sub-micrometer strontium-contained bioactive microspheres through modulating macrophage phenotypes

Fujian Zhao; Bo Lei; Xian Li; Yunfei Mo; Renxian Wang; Dafu Chen; Xiaofeng Chen

doi:10.1016/j.biomaterials.2018.06.004

Promoting in vivo early angiogenesis with sub-micrometer strontium-contained bioactive microspheres through modulating macrophage phenotypes

Biomaterials. 2018 Sep:178:36-47. doi: 10.1016/j.biomaterials.2018.06.004. Epub 2018 Jun 8.

Authors

Fujian Zhao¹, Bo Lei², Xian Li¹, Yunfei Mo¹, Renxian Wang³, Dafu Chen⁴, Xiaofeng Chen⁵

Affiliations

¹ Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510641, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou, 510006, China; Key Laboratory of Biomedical Materials and Engineering, Ministry of Education, South China University of Technology, Guangzhou, 510006, China.
² Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710000, China; Instrument Analysis Center, Xi'an Jiaotong University, Xi'an, 710054, China; State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710054, China. Electronic address: [email protected].
³ Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Orthopaedics and Traumatology, Beijing Jishuitan Hospital, Beijing, 100035, China.
⁴ Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Orthopaedics and Traumatology, Beijing Jishuitan Hospital, Beijing, 100035, China. Electronic address: [email protected].
⁵ Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510641, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou, 510006, China; Key Laboratory of Biomedical Materials and Engineering, Ministry of Education, South China University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].

PMID: 29908343
DOI: 10.1016/j.biomaterials.2018.06.004

Abstract

Early vascularization capacity of biomaterials plays an essential role in efficient wound healing and tissue regeneration, especially in large tissue tension implanting position such as bone augmentation. Strontium-contained silica-based bioactive materials have shown the role of promoting angiogenesis by stimulating osteoblasts to secrete angiogenesis related cytokines. However, osteoblasts have little effect on early angiogenesis due to the inflammatory reaction of implantation site. Here, for the first time, we found that the monodispersed strontium-contained bioactive glasses microspheres (SrBGM) could significantly promote the early angiogenesis through regulating macrophage phenotypes. After being stimulated with SrBGM in vitro, RAW cells (macrophages) presented a trend towards to M2 phenotype and expressed high level of platelet-derived growth factor-BB (PDGF-BB). Moreover, the RAW conditioned medium of SrBGM significantly enhanced the angiogenic capacity of HUVECs. The in vivo early vascularization studies showed that significant new vessels were observed at the center of SrBGM-based scaffolds after implantation for 1 week in a bone defect model of rats, suggesting their enhanced early vascularization. Due to the efficient vascularization, the in vivo new bone formation was promoted significantly. Our study may provide a novel strategy to promote the early vascularization of biomaterials through modulating the microphage phenotypes, which has wide applications in various tissue regeneration and wound healing.

Keywords: Angiogenesis; Bioactive glasses; Bone regeneration; Macrophage phenotypes; Micro-nano particles; Strontium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Regeneration / drug effects
Cell Polarity / drug effects
Culture Media, Conditioned / pharmacology
Glass / chemistry
Human Umbilical Vein Endothelial Cells / drug effects
Humans
Implants, Experimental
Macrophages / cytology*
Macrophages / drug effects
Male
Mice
Mice, Inbred BALB C
Microspheres*
Neovascularization, Physiologic / drug effects*
Particle Size*
Phenotype
RAW 264.7 Cells
Rats, Sprague-Dawley
Strontium / pharmacology*
Tissue Scaffolds / chemistry

Substances

Culture Media, Conditioned
Strontium