title: The promotion of angiogenesis induced by three-dimensional porous beta-tricalcium phosphate scaffold with different interconnection sizes via activation of PI3K/Akt pathways.
abstract: The porous architectural characteristics of biomaterials play an important role in scaffold revascularization. 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 in vitro and in vivo. We incubated human umbilical vein endothelial cells on scaffolds with interconnections of various sizes. Results showed that scaffolds with a 150 μm 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. In vivo study was performed on rabbit implanted with scaffolds into the bone defect on femoral condyles. Implantation with scaffolds with 150 μm interconnection size significantly improved neovascularization as shown by micro-CT as compared to scaffolds with 100 and 120 μm 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 μm 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.
authors: Department of Orthopedics, Xijing Hospital, Forth Military Medical University, Xi'an, Shaanxi, PR China.
authors: Xin
authors: X
authors: Xiao
authors: The State Key Laboratory of Cancer Biology, Department of Immunology, Forth Military Medical University, Xi'an, Shaanxi, PR China.
authors: Wei
authors: W
authors: Wang
authors: Department of Orthopedics, Xijing Hospital, Forth Military Medical University, Xi'an, Shaanxi, PR China.
authors: Dong
authors: D
authors: Liu
authors: Department of Orthopedics, Xijing Hospital, Forth Military Medical University, Xi'an, Shaanxi, PR China.
authors: Haoqiang
authors: H
authors: Zhang
authors: Department of Orthopedics, Xijing Hospital, Forth Military Medical University, Xi'an, Shaanxi, PR China.
authors: Peng
authors: P
authors: Gao
authors: Department of Orthopedics, Xijing Hospital, Forth Military Medical University, Xi'an, Shaanxi, PR China.
authors: Lei
authors: L
authors: Geng
authors: Department of Orthopedics, Xijing Hospital, Forth Military Medical University, Xi'an, Shaanxi, PR China.
authors: Yulin
authors: Y
authors: Yuan
authors: Shanghai Bio-lu Biomaterials Co., Ltd., Shanghai, P.R. China.
authors: Jianxi
authors: J
authors: Lu
authors: Department of Orthopedics, Xijing Hospital, Forth Military Medical University, Xi'an, Shaanxi, PR China.
authors: Zhen
authors: Z
authors: Wang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016062:Porosity; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship; D013499:Surface Properties; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt; D042461:Vascular Endothelial Growth Factor A; C485817:beta-tricalcium phosphate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one