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However, no consensus exists regarding optimal interconnection sizes for vascularization and its scaffold bioperformance with different interconnection sizes. Therefore, a series of disk-type beta-tricalcium phosphates with the same pore sizes and variable interconnections were produced to evaluate how the interconnection size influenced biomaterial vascularization <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. We incubated human umbilical vein endothelial cells on scaffolds with interconnections of various sizes. Results showed that scaffolds with a 150\u2005\u03bcm interconnection size ameliorated endothelial cell function evidenced by promoting cell adhesion and migration, increasing cell proliferation and enhancing expression of platelet-endothelial cell adhesion molecules and vascular endothelial growth factor. <jats:italic>In vivo<\/jats:italic> study was performed on rabbit implanted with scaffolds into the bone defect on femoral condyles. Implantation with scaffolds with 150\u2005\u03bcm interconnection size significantly improved neovascularization as shown by micro-CT as compared to scaffolds with 100 and 120\u2005\u03bcm interconnection sizes. Moreover, the aforementioned positive effects were abolished by blocking PI3K\/Akt\/eNOS pathway with LY-294002. Our study explicitly demonstrates that the scaffold with 150\u2005\u03bcm interconnection size improves neovascularization via the PI3K\/Akt pathway and provides a target for biomaterial inner structure modification to attain improved clinical performance in implant vascularization.<\/jats:p>","DOI":"10.1038\/srep09409","type":"journal-article","created":{"date-parts":[[2015,3,23]],"date-time":"2015-03-23T10:04:42Z","timestamp":1427105082000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":156,"title":["The promotion of angiogenesis induced by three-dimensional porous beta-tricalcium phosphate scaffold with different interconnection sizes via activation of PI3K\/Akt pathways"],"prefix":"10.1038","volume":"5","author":[{"given":"Xin","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoqiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,23]]},"reference":[{"key":"BFsrep09409_CR1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/35025220","volume":"407","author":"P Carmeliet","year":"2000","unstructured":"Carmeliet, P. & Jain, R. 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