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Nano-hydroxyapatite formation via co-precipitation with chitosan-g-poly（N-isopropylacrylamide） in coil and globule states for tissue engineering application

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Frontiers of Chemical Science and Engineering 2013年第4期7卷 388-400页

作者： Yang YU Hong ZHANG Hong SUN Dandan XING Fanglian YAO School of Chemical Engineering and Technology Key Laboratory of Systems Bioengineering of Ministry of Education Tianjin University Tianjin 300072 China Consolidated Research Institute for Advanced Science and Medical Care Waseda University (ASMeW) Shinjuku-ku Tokyo 162-0041 Japan Basic Medical College Hebei United University Tangshan 063000 China

With the excellent biocompatibility and osteo- conductivity, nano-hydroxyapatite （nHA） has shown significant prospect in the biomedical applications. Con- trolling the size, crystallinity and surface properties of nHA crystals is a critical challenge in the design of HA based biomaterials. With the graft copolymer of chitosan and poly（N-isopropylacrylamide） in coil and globule states as a template respectively, a novel composite from chitosan-g-poly（N-isopropylacrylamide） and nano-hydro- xyapatite （CS-g-PNIPAM/nHA） was prepared via co- precipitation. Zeta potential analysis, thermogravimetric analysis and X-ray diffraction were used to identify the formation mechanism of the CS-g-PNIPAM/nHA compo- site and its morphology was observed by transmission electron microscopy. The results suggested that the physical aggregation states of the template polymer could induce or control the size, crystallinity and morphology of HA crystals in the CS-g-PNIPAM/nHA composite. The CS-g-PNIPAM/nHA composite was then introduced to chitosan-gelatin （CS-Gel） polyelectronic complex and the cytocompatibility of the resulting CS- Gel/composite hybrid film was evaluated. This hybrid film was proved to be favorable for the proliferation of MC 3T3-E1 cells. Therefore, the CS-g-PNIPAM/nHA compo- site is a potential biomaterial in bone tissue engineering.

关键词： chitosan poly（N-isopropylacrylamide）,hydroxyapatite coil globule bone tissue engineering

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Milk fat globule epithelial growth factorⅧ(MFG-E8)sustains survival of cancer cells by prompting tumor angiogenesis and suppressing host immunities

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Oncology and Translational Medicine 2017年第1期3卷 31-37页

作者： Keke Nie Shichao Liu Ling Zhang Zhongfa Zhang Xiao Zou Youxin Ji Oncology Department Qingdao Cancer HospitalQingdao 266042China Oncology Department Qingdao Central HospitalThe 2nd Affiliated Hospital of Qingdao UniversityQingdao 266042China

Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.

关键词： milk fat globule epithelial growth factor VIII (MFG-E8) carcinoma target therapy angiogenesis apoptosis

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