title: Effect of nano-structured bioceramic surface on osteogenic differentiation of adipose derived stem cells.
abstract: Tissue engineering strategies to construct vascularized bone grafts potentially revolutionize the treatment of massive bone loss. The surface topography of the grafts plays critical roles on bone regeneration, while adipose derived stem cells (ASCs) are known for their capability to promote osteogenesis and angiogenesis when applied to bone defects. In the present study, the effects of hydroxyapatite (HAp) bioceramic scaffolds with nanosheet, nanorod, and micro-nano-hybrid (the hybrid of nanorod and microrod) surface topographies on attachment, proliferation and osteogenic differentiation, as well as the expression of angiogenic factors of rat ASCs were systematically investigated. The results showed that the HAp bioceramic scaffolds with the micro-/nano-topography surfaces significantly enhanced cell attachment and viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteogenic markers and angiogenic factors of ASCs. More importantly, the biomimetic feature of the hierarchical micro-nano-hybrid surface topography showed the highest stimulatory effect. The activation in Akt signaling pathway was observed in ASCs cultured on HAp bioceramics with nanorod, and micro-nano-hybrid surface topographies. Moreover, these induction effects could be repressed by Akt signaling pathway inhibitor LY294002. Finally, the in vivo bone regeneration results of rat critical-sized calvarial defect models confirmed that the combination of the micro-nano-hybrid surface and ASCs could significantly enhance both osteogenesis and angiogenesis as compared with the control HAp bioceramic scaffold with traditional smooth surface. Our results suggest that HAp bioceramic scaffolds with micro-nano-hybrid surface can act as cell carrier for ASCs, and consequently combine with ASCs to construct vascularized tissue-engineered bone.
authors.affiliation: Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors.forename: Lunguo
authors.initials: L
authors.lastname: Xia
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Lin
authors.affiliation: Oral Bioengineering Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Fang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors.forename: Yuanjin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Oral Bioengineering Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors.forename: Maolin
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Oral Bioengineering Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China. Electronic address: jchang@mail.sic.ac.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China. Electronic address: zhzhy@omschina.org.cn.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002516:Ceramics / Q000494:pharmacology*; D017886:Durapatite / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013194:Staining and Labeling; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D005456:Fluorescent Dyes; D017886:Durapatite; D051057:Proto-Oncogene Proteins c-akt; D000469:Alkaline Phosphatase
keywords: Akt signaling pathway; Angiogenesis; Bone tissue engineering; Hydroxyapatite bioceramic scaffolds; Osteogenesis; Surface topography