研发基础、主要研究成果
1.1. 智能型心血管支架
项目申请人及成员主要研究方向聚焦于1)心血管动脉粥样硬化病理发病机制、以及用于心血管疾病治疗的具有病变血管组织再生修复及病灶治愈功能的冠脉、外周及颅内血管支架;2)新型可降解金属基血管支架研发;3)基于微流控芯片的细胞作用机制。以通讯/第一作者在包括PNAS(IF=11.205),Nature Communications(IF=14.919),Advanced Science(IF=16.806),Research,Biomaterials(IF=12.479),Bioactive Materials(IF=14.593)及Small(IF=13.281)等国际知名期刊上共发表SCI收录论文48篇(论文平均IF=9.4542,其中IF>10的论文22篇,IF=8-10的论文8篇)。获得授权发明专利19项(包括美国发明专利1项,其中转让专利5项)。主导研发的具有完全自主知识产权的“镁合金血管支架制造专有技术”已成功实现转让(转让费:1500万,贡献排名第1)。基于该“一氧化氮催化释放的内皮功能仿生血管支架涂层技术”于2019年成立了广州南创珠峰医疗科技有限公司,本人担任该公司董事会董事(负责支架涂层技术)。目前,基于该核心涂层技术研发的新一代心血管支架进入到产业化工程和申报检验阶段。
1. 杨志禄
1)教育经历:
1. 2009-09至2014-06,西南交通大学,材料学,博士
2. 2005-09至2008-06,西南交通大学,材料物理化学,硕士
3. 2001-09至2005-06,南昌航空大学,高分子材料与工程,学士
2)工作经历:
1. 2021-06至今,南方医科大学,附属东莞医院,研究员
2. 2019-12至2021-06,西南交通大学,材料科学与工程学院,研究员
3. 2015-04至2019-12,西南交通大学,材料科学与工程学院,副教授
3)近年来主持或参加的项目/课题:
1. 南方医科大学附属东莞医院高层次人才支持与发展计划(项目号:K202102),具有调控病变血管再生修复功能的血管支架研究,2021/06-2024/06,300万,主持(在研)。
2. 国家自然科学基金--面上项目(项目号:82072072),具有一氧化氮催化和免疫抑制剂可控释放的聚肟氨酯涂层改性镁合金血管支架研究,2021/01-2024/12,56万,主持(在研)。
3. 四川省国际科技创新合作项目(项目号:2021YFH0056),具有仿生内皮功能和细胞外基质结构的水凝胶支架涂层构建及抗再狭窄和抗血栓研究,2021/03-2023/03,30万,主持(在研)。
4. 四川省杰出青年基金(项目号:2016JQ0027),基于原位一氧化氮催化释放的内皮功能仿生涂层血管支架研究,2016/03-2019/03,50万,主持(结题)。
5. 国家自然科学基金--面上项目(项目号:31570957),原位催化持续、稳定、可控释放一氧化氮的内皮功能仿生涂层研究,2016/01-2019/12,61万,主持(结题)。
6. 国家自然科学基金--青年科学基金项目(项目号:81501596),具有原位催化一氧化氮释放的内皮功能仿生涂层用于心血管支架表面改性研究,2016/01-2018/12,18万,主持(结题)。
4)代表性研究成果和学术奖励情况:
成果技术转让:
① 镁合金血管支架制造专有技术(转让费:1500万,2019年,1/13)
获奖:
① 具有调控内膜增生和内皮再生修复功能的血管支架及临床应用, 中国生物材料学会, 科技进步, 省部一等奖, 2021 (2/7)
代表性科研论文:
1. Jie Sun, Yingkang Huang, Huan Zhao, Junjie Niu, Xuwei Ling, Can Zhu, Lin Wang, Huilin Yang, Zhilu Yang*, Guoqing Pan*, Qin Shi*. Bio-clickable mussel-inspired peptides improve titanium-based material osseointegration synergistically with immunopolarization-regulation. Bioactive Materials. 2022;9:1-14 (IF=14.593).
2. Ying Wang, Ranjith Kumar Kankala, Caiwen Ou, Aizheng Chen*, Zhilu Yang*. Advances in hydrogel-based vascularized tissues for tissue repair and drug screening. Bioactive Materials. 2022;9:198-220 (IF=14.593).
3. Yin Chen#, Peng Gao#, Lu Huang, Xing Tan, Ningling Zhou, Tong Yang, Hua Qiu, Xin Dai, Sean Michael, Qiufen Tu, Nan Huang, Zhihong Guo, Jianhua Zhou*, Zhilu Yang*, Hongkai Wu*. A tough nitric oxide-eluting hydrogel coating suppresses neointimal hyperplasia on vascular stent. Nature Communications. 2021;12:7079 (IF=14.919).
1. Qing Ma#, Xiuying Shi#, Xing Tan, Rui Wang, Kaiqin Xiong, Manfred F. Maitz, Yuanyuan Cui, Zhangmei Hu, Qiufen Tu*, Nan Huang, Li Shen*, Zhilu Yang*. Durable endothelium-mimicking coating for surface bioengineering cardiovascular stents. Bioactive Materials. 2021;12:4786-4800 (IF=14.593).
2. Han Yu#, Hua Qiu#, Wenmei Ma, Manfred F. Maitz, Qiufen Tu, Kaiqin Xiong, Jiang Chen*, Nan Huang*, Zhilu Yang*. Endothelium-Mimicking Surface Combats Thrombosis and Biofouling via Synergistic Long- and Short-Distance Defense Strategy. Small. 2021;2100729. (IF=13.281).
3. Wenxuan Wang#, Lei Lu#, Bei Ho Pan#, Xiangyang Li, Zeyu Du, Manfred F. Maitz, Qiufen Tu*, Nan Huang, Xin Zhao*, Zhilu Yang*. Self-protonating, plasma polymerized, superimposed multi-layered biomolecule nanoreservoir as blood-contacting surfaces. Chemical Engineering Journal. 2021;410:128313. (IF=13.273).
4. Hua Qiu, Qiufen Tu, Peng Gao, Xiangyang Li, Manfred F. Maitz, Kaiqin Xiong*, Nan Huang, Zhilu Yang*. Phenolic-amine chemistry mediated synergistic modification with polyphenols and thrombin inhibitor for combating the thrombosis and inflammation of cardiovascular stents. Biomaterials. 2021;269:120626 (IF=12.479).
5. Han Yu, Shaoxing Yu, Hua Qiu, Peng Gao, Yingzhong Chen, Xin Zhao, Qiufen Tu, Minggang Zhou*, Lin Cai, Nan Huang, Kaiqin Xiong*, Zhilu Yang*. Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions. Bioactive Materials. 2021;6:1618-1627 (IF=14.593).
6. Nan Lyu, Zeyu Du, Hua Qiu, Peng Gao, Qin Yao, Kaiqin Xiong, Qiufen Tu, Xiangyang Li, Binghai Chen, Guoqing Pan*, Nan Huang*, Zhilu Yang*. Mimicking the Nitric Oxide-Releasing and Glycocalyx Functions of Endothelium on Vascular Stent Surfaces. Advanced Science. 2020;7:202002330 (IF=16.806).
7. Zhilu Yang#, Xin Zhao#, Rui Hao, Qiufen Tu, Xiaohua Tian, Yu Xiao, Kaiqin Xiong, Miao Wang, Yonghai Feng, Nan Huang*, Guoqing Pan*. Bio-clickable and Mussel Adhesive Peptide Mimics for Engineering Vascular Stent Surfaces. PNAS. 2020;117:16127-16137 (IF=11.205).
8. Yu Xiao, Wenxuan Wang, Xiaohua Tian, Xing Tan, Tong Yang, Peng Gao, Kaiqing Xiong, Qiufen Tu, Miao Wang, Manfred F. Maitz, Nan Huang, Guoqing Pan*, Zhilu Yang*. A Versatile Surface Bioengineering Strategy Based on Mussel-Inspired and Bioclickable Peptide Mimic. Research. 2020;7236946.
9. Ying Yang, Peng Gao, Juan Wang, Qiufen Tu, Long Bai, Kaiqin Xiong, Hua Qiu, Xin Zhao, Manfred F. Maitz, Huaiyu Wang, Xiangyang Li, Qiang Zhao, Yin Xiao, Nan Huang*, Zhilu Yang*. Endothelium-Mimicking Multifunctional Coating Modified Cardiovascular Stents via a Stepwise Metal-Catechol-(Amine) Surface Engineering Strategy. Research. 2020;9203906.
10. Peng Gao, Hua Qiu, Kaiqin Xiong, Xiangyang Li, Qiufen Tu, Huaiyu Wang, Nan Lyu, Xiao Chen, Nan Huang*, Zhilu Yang*. Metal-Catechol-(Amine) Networks for Surface Synergistic Catalytic Modi?cation: Therapeutic Gas Generation and Biomolecule Grafting. Biomaterials. 2020;248:119981 (IF=12.479).
11. Xiangyang Li#, Jingxia Liu#, Tong Yang, Hua Qiu, Lei Lu, Qiufen Tu, Kaiqing Xiong, Nan Huang*, Zhilu Yang*. Mussel-inspired “built-up” surface chemistry for combining nitric oxide catalytic and vascular cell selective properties. Biomaterials. 2020;241:119904 (IF=12.479).
12. Tong Yang, Zeyu Du, Hua Qiu, Peng Gao, Xin Zhao, Huaiyu Wang, Qiufen Tu, Kaiqin Xiong, Nan Huang, Zhilu Yang*. From surface to bulk modification: Plasma polymerization of amine-bearing coating by synergic strategy of biomolecule grafting and nitric oxide loading. Bioactive Materials. 2020;5:17-25 (IF=14.593).
13. Qiufen Tu#, Xin Zhao#, Shuai Liu, Xiangyang Li, Qiang Zhang, Han Yu, Kaiqin Xiong, Nan Huang, Zhilu Yang*. Spatiotemporal Dual-Delivery of Therapeutic Gas and Growth Factor for Prevention of Vascular Stent Thrombosis and Restenosis. Applied Materials Today. 2020;19:100546 (IF=10.041).
14. Hua Qiu#, Pengkai Qi#, Xing Tan, Yu Xiao, Jingxia Liu, Lei Lu, Peng Gao, Ying Yang, Nan Huang*, Zhilu Yang*. Biomimetic Engineering Endothelium-like Coating on Cardiovascular Stent through Heparin and Nitric Oxide-Generating Compound Synergic Modification Strategy. Biomaterials. 2019;207:10-22 (IF=12.479).
15. Feng Zhang#, Qiang Zhang#, Xiangyang Li, Nan Huang, Xin Zhao*, Zhilu Yang*. Mussel-inspired dopamine-CuII coatings for sustained in situ generation of nitric oxide for prevention of stent thrombosis and restenosis. Biomaterials. 2019;194:117-129 (IF=12.479).
16. Xiangyang Li, Peng Gao, Jianying Tan, Kaiqin Xiong, Changjiang Pan, Hongkai Wu, Yin Chen, Zhilu Yang*, Nan Huang*. Assembly of Metal-Phenolic/Catecholamine Networks for Synergistically Anti-Inflammatory, Antimicrobial and Anticoagulant Coatings. ACS Applied Materials & Interfaces. 2018;10:40844-40853 (IF=9.229).
17. Zhilu Yang*, Ying Yang, Kaiqin Xiong, Jin Wang, Haeshin Lee*, Nan Huang*, Metal-Phenolic Surfaces for Generating Therapeutic Nitric Oxide Gas. Chemistry of Materials. 2018;30:5220-5226 (IF=9.811).
18. Zhilu Yang*, Ying Yang, Li Zhang, Kaiqin Xiong, Xiangyang Li, Feng Zhang, Jin Wang, Xin Zhao*, Nan Huang*, Mussel-inspired Catalytic Selenocystamine-Dopamine Coatings for Long-Term Generation of Therapeutic Gas on Cardiovascular Stents. Biomaterials. 2018;178:1-10 (IF=12.479).
19. Xiangyang Li, Hua Qiu, Peng Gao, Ying Yang, Zhilu Yang*, Nan Huang*, Synergetic coordination- and catecholamine chemistry for catalytic generation of nitric oxide on vascular stents. NPG Asia Materials. 2018;10:482-496 (IF=10.481).
20. Ying Yang, Xiangyang Li, Hua Qiu, Ping Li, Manfred F. Maitz, Tianxue You, Ru Shen, Zhilu Yang*, Wenjie Tian*, and Nan Huang*. Polydopamine modified TiO2 nanotube arrays for long term controlled elution of bivalirudin and improved hemocompatibility. ACS Applied Materials & Interfaces. 2018;10:7649?7660 (IF=9.229).
21. Zhilu Yang*, Hua Qiu, Xiangyang Li, Peng Gao, Nan Huang*, Plant-inspired gallolamine catalytic surface chemistry for engineering an efficient nitric oxide generating coating. Acta Biomaterialia. 2018;76:89-98 (IF=8.947).
22. Zhilu Yang*, Ying Yang, Kaiqin Xiong, Xiangyang Li, Pengkai Qi, Qiufen Tu, Fengjuan Jing, Yajun Weng, Jin Wang*, Nan Huang*. Nitric oxide producing coating mimicking endothelium function for multifunctional vascular stents. Biomaterials. 2015;63:80-92 (IF=12.479).
23. Zhilu Yang*, Kaiqin Xiong, Pengkai Qi, Ying Yang, Qiufen Tu, Jin Wang*, Nan Huang*. Gallic acid tailoring surface functionalities of plasma-polymerized allylamine-coated 316L SS to selectively direct vascular endothelial and smooth muscle cell fate for enhanced endothelialization. ACS Applied Materials & Interfaces. 2014;6:2647-2656 (IF=9.229).
24. Ying Yang, Pengkai Qi, Feng Wen, Xiangyang Li, Qin Xia, Manfred F. Maitz, Zhilu Yang*, Ru Shen, Qiufen Tu, Nan Huang*. Mussel-inspired one-step adherent coating rich in amine groups for covalent immobilization of heparin: hemocompatibility, growth behaviors of vascular cells and tissue response. ACS Applied Materials & Interfaces. 2014;6:14608-14620 (IF=9.229).
25. Zhilu Yang#,*, Ying Yang#, Wei Yan, Qiufen Tu*, Jin Wang*, Nan Huang. Construction of polyfunctional coatings assisted by gallic acid to facilitate co-immobilization of diverse biomolecules. ACS Applied Materials & Interfaces. 2013;5:10495-10501 (IF=9.229).
26. Zhilu Yang, Qiufen Tu*, Manfred F. Maitz, Shou Zhou, Jin Wang, Nan Huang*. Direct thrombin inhibitor-bivalirudin functionalized plasma polymerized allylamine coating for improved biocompatibility of vascular devices. Biomaterials. 2012;33:7959-7971 (IF=12.479).
27. Zhilu Yang, Qiufen Tu, Ying Zhu, Rifang Luo, Xin li, Yichu Xie, Manfred F. Maitz, Jin Wang*, Nan Huang*. Mussel-inspired coating of polydopamine directs endothelial and smooth muscle cell fate for re-endothelialization of vascular devices. Advanced Healthcare Materials. 2012;1:548-559 (IF=9.933).
28. Zhilu Yang*, Qiufen Tu, Jin Wang*, Nan Huang*. The role of heparin binding surface in the direction of endothelial and smooth muscle cell fate and re-endothelialization. Biomaterials. 2012;33:6615-6625 (IF=12.479).
29. Zhilu Yang, Jin Wang*, Rifang Luo, Manfred F. Maitz, Fengjuan Jing, Hong Sun, Nan Huang. The covalent immobilization of heparin to pulsed-plasma polymeric allylamine films on 316L stainless steel and the resulting effects on hemocompatibility. Biomaterials. 2010;31:2072–2083 (IF=12.479).
代表性发明专利:
1. 杨志禄,高鹏,黄楠,李向阳,熊开琴,涂秋芬,刘静霞,一种血管支架及其制备方法和应用,授权时间2021年12月07日,中国,发明专利号:ZL201911292435.7。
2. 黄楠,于绍兴,杨志禄,涂秋芬,熊开琴,高鹏,邱华,抗菌抗凝血涂层及其制备方法和医用材料,授权时间2021年8月13日,中国,发明专利号:ZL202010652100.8。
3. 杨志禄,黄楠,杨彤,杜泽煜,熊开琴,涂秋芬,多功能薄膜的制备方法及多功能薄膜材料,授权时间2020年9月4日,中国,发明专利号:ZL201910194089.2。
4. 杨志禄,黄楠,王进,翁亚军,一种构建一氧化氮催化型粘附涂层的方法,授权时间 2020年8月11日,美国,发明专利号:PCT/ZL2015/086773。
5. 涂秋芬、夏俊秋、杨志禄、乔峰、黄楠、谭星、高鹏、邱华、陈枭、杨彤,一种抗凝血材料及其制备方法,授权时间 2020年8月11日,中国,发明专利号:ZL201910230258.3。
6. 杨志禄,黄楠,杨彤,光刻胶、其制备方法、应用和医用材料表面的改性方法,授权时间2020年6月30日,中国,发明专利号:ZL201910435664.3。
7. 杨志禄,乔峰,黄楠,涂秋芬,夏俊秋,邱华,高鹏,富胺基儿茶酚胺化合物及其制备方法、富胺基表面改性产品、材料及其浸涂方法,授权时间2020年6月16日,中国,发明专利号:ZL201910309688.4。
8. 杨志禄,郭倩如,黄楠,涂秋芬,熊开琴,赵昕,区域选择性可控化固定双分子薄膜及其制备方法,授权时间2020年6月9日,中国,发明专利号:ZL201910027335.5。
9. 杨志禄,郝蕊,潘国庆,黄楠,涂秋芳,熊开琴,具有NO催化释放与EPCs捕获功能的生物材料及其制备方法,授权时间2020年1月31日,中国,发明专利号:ZL201910194707.3。
10. 黄楠,杨志禄,王进,齐鹏凯,涂秋芬,杨莹,熊开琴,翁亚军,李龙,李亚龙,一种具有一氧化氮(NO)催化活性的涂层的制备方法,授权时间 2017年5月17日,中国,发明专利号:ZL 201510020342.4。
11. 黄楠,杨志禄,王进,齐鹏凯,涂秋芬,杨莹,熊开琴,翁亚军,李龙,李亚龙,一种具有一氧化氮(NO)催化活性的材料的制备方法,授权时间 2016年10月5日,中国,发明专利号:ZL 201410394884.3。
12. 黄楠,杨志禄,王进,齐鹏凯,涂秋芬,杨莹,熊开琴,翁亚军,李龙,李亚龙,一种具有可控一氧化氮催化释放的含有铜离子与多酚配位物的螯合物材料的制备方法,授权时间 2016年8月24日,中国,发明专利号:ZL 201410394483.8。
13. 黄楠,杨志禄,王进,齐鹏凯,涂秋芬,杨莹,熊开琴,翁亚军,李龙,李亚龙,一种具有可控一氧化氮催化释放的铜离子与多酚配位物的螯合物涂层的制备方法,授权时间 2016年5月18日,中国,发明专利号:ZL 201410393778.3。
14. 王进,罗日方,杨志禄,黄楠,翁亚军,赵元聪,冷永祥,杨苹,一种具有诱导催化内源性NO释放功能的抗凝血材料制备方法,授权时间2015年11月25日,中国,发明专利号ZL 201410394981.2。
15. 王进,杨志禄,黄楠,冷永祥,赵元聪,一种具有高生物功能性的肝素化界面材料制备方法,授权时间2013年7月31日,中国,发明专利号:ZL 201110195704.5。
16. 王进,杨志禄,冷永祥,孙鸿,黄楠,基于类聚乙二醇的可回收下腔静脉滤器表面膜制备方法,授权时间2013年6月12日,中国,发明专利号:ZL 201110277736.X。
17. 王进,杨志禄,黄楠,涂秋芬,陈思,罗日方,一种富含氨基、羧基和醌基的多类功能团的生物医用材料制备方法,授权时间 2014年11月26日,中国,发明专利号:ZL 201210147674.5。
18. 王进,杨志禄,吕磊,周烁,黄楠,一种抗凝血材料的制备方法,授权时间 2014年7月23日,中国,发明专利号:ZL 201210147263.6。
19. 黄楠,翁亚军,杨志禄,宋强,罗日方,冷永祥,杨萍,王进,陈俊英,孙鸿,吴熹,李全利,一种基于聚多巴胺的生物功能化改性方法,授权时间 2013年4月3日,中国,发明专利号:ZL 201010588977.1。