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Team of Biomaterial Process and Engineering

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Brief Introduction

Biomaterials are the substances which, alone or as part of a complex system, are derived from living system or used for biomedical application, such as protein, nucleic acid, polysaccharide, lipid composition, and other biocompatible materials.The team of biomaterial process and engineering focuses on the scientific study and technical obstacles in biomaterial-related process and engineering. The team members have made good efforts for extraction and separation of biological materials with high purity and bioactivity, controllable degradation and modification of biomolecules, assembly and formulation of these biomolecules into desired structure, and applications of these products from bench to practice. Based on the discovery at molecular level and the breakthrough in the manufacturing process, they have made great success in the development of biological drug, tissue engineering, drug carrier, vaccine adjuvant, functional food, and pesticide, which are playing an important role in human health and food safety.

Research Activities

1. Exploration of novel particle adjuvant and mucosal adjuvant

Aiming at the deficiency of aluminum adjuvant (the only FDA approved adjuvant for human use), the team members devoted themselves to exploring novel particle adjuvant and mucosal adjuvant. To endow the particle with uniform size and tunable structure, they successfully developed membrane emulsification technique and new preparation process. Based on these, they unsealed the size/structure-activity relationship between particle and immune response. To overcome the hurdles in mucosal vaccine (rapid clearance in nasal cavity and poor penetration in epithelial cells), they also developed a thermal-sensitive hydrogel system. The thermal-sensitive property could anchor the antigen to mucosal surface, and further improve the antigen penetration due to opened tight conjugations between epithelial cells. As-developed micro/nano particles and thermal-sensitive hydrogel enabled us to construct a series of high-performance vaccines for prevention or cure of influenza, hepatitis B, hand foot and mouth disease, diabetes, and tumor.

2. Key technologies of preparation and application for konjac glucomannan microspheres

China is the largest country in the world for planting and producing konjak. The main component, konjac glucomannan (KGM), is a natural polysaccharide with excellent properties. However, it is still in the early stages of processing with meager profits. The team developed a series of KGM microsphere products with higher value for separation medium, microcarrier for cell culture, enzyme immobilization carrier, and so on. They mastered the know-how of preparation of KGM microspheres with controllable structure according to the demand of application. They also solved the key problems in the process of scale-up. These novel KGM microspheres have led to good results in more than 30 companies.

3. Development of forage composite enzymes

The team focuses on forage composite enzymes derived from marine microorganisms. Aiming at degradation of complex structure of corn, wheat, soybean meal, and other cell wall of non-starch polysaccharides, they efficiently screened

Team of Biomaterial Process and Engineering

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glucosidase by using metagenomic technology and ultra-high throughput screening platform in chip laboratory. They also established high expression system of enzymes and broke up the key technical bottleneck in fully using of starch and non-starch polysaccharide. They obtained a number of forage composite enzymes with specific effects and ruled the related product quality evaluation methods to ensure the biological efficiency of raw feed materials. Their research provided a new way of solving the shortage of forage resource, reducing environment pollution, and protecting the quality of livestock, poultry, and aquatic products.

4. Research of chitosan adjuvant

Chitosan has attracted a booming interesting in biomedical application due to its excellent properties of bio-degradability, bio-compatibility, and safety. The team focuses on innovative preparation method of chitosan gel, micro/nano particles with uniform size, and chitosan oligosaccharide with controllable molecular weight. To realize high value utilization, these chitosan-based products are being explored as immune adjuvant for human, livestock, and poultry.

5. Key technology of targeted delivery of gene drugs for tumor therapy

The team members focus on targeted delivery of gene drugs for tumor therapy. Based on non-viral vectors, (such as polymer particles and liposomes), they ingeniously designed and constructed several targeted delivery systems with good biocompatibility, excellent targeting delivery, and controlled release. These systems can significantly improve the efficacy of gene therapy drugs in vivo. They also studied druggability of these delivery systems and established the evaluation standard to promote the gene therapy from bench to clinic.

Infrastructure

The team has 24 core members, including 5 professors, 15 associate professors, 4 assistant professors. According to their outperformance, they have been supported by the National Science Foundation for Distinguished Young Scholars, Global Youth Experts Program, Hundred Talents Program, Beijing Nova Program, and Youth Innovation Promotion Association.

The team sets up excellent instrument plat form for biomaterial preparation, characterization, and evaluation. It is worth mentioning that the team has successfully designed and established a series of membrane emulsion equipment for applications from laboratory to industry, and expanded our technology and equipment to more than 80’s enterprises to develop new science and breakthrough technologies. The equipment for scale-up has been used in Zhejiang ZhengGuang

Membrane emulsion equipments from laboratory scale to industry scale

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Biodistribution of chitosan microspheres with different particle size

A variety of microfluidic chip and chip control / detection system

Industrial Co.,Ltd. (China), Taiwan Etemal Chemical Industry Limited Company, Unilever of UK, and so forth. We also succeed in academic and commercial corporations with international famous companies, as for example, two research projects with Unilever, and one patent ZL 200710098700.9 transfer to GE Healthcare.

Research Progress

1. Microsphere and microcapsule with uniformed size and controllable structure for separation and drug delivery

Uniformed chitosan microspheres with novel structures and the corresponding optimized release profile

To solve the problems sourced traditional non-uniform particles (prepared by stirr ing method), the team successfully developed membrane emulsion technology, which offered a mild and simple way for the preparation of uniform-sized microspheres and microcapsules. These particles can be further endowed with controllable structure by optimizing the preparation process. Based on the uniformity and controllability of particle size and structure, systematical studies have been carried on to clarify how the physicochemical properties affect the purification and therapy effect. Accordingly, a series of high-performance separation medium and drug carrier have been developed.

2 . P latform of ul tra-high throughput screening and glycosidase library for sugar bioengineering tool enzyme

Using natural polysacchar ide as raw mater ia ls , preparation of oligosaccharide with specific polymerization degree and structure is a main tendency of development of oligosaccharide. The core technique is the selection of enzyme for controllable degradation. The team established a glycosidase library (163 enzymes) from various kinds of natural polysaccharide by using metagenomic integrated

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3. Biomaterial process and engineering based on peptide and protein self-assembly

The team focused on controllable preparation of biomaterials with various structure and function by self-assembly technology. They also studied the fundamental mechanisms of self-assembly which contributes to reveal the basic law of life and the pathogenesis of many major diseases. Their design and functionalization at the molecular level had unique advantages in developing novel smart materials, nano devices, and biomedical materials. Combined with uniform-sized controlling technology, the functional self-assembled vaccine achieved excellent results in immunotherapy.

microfluidic chip technology, and obtained a lot of functional oligosaccharide products. Further researches have been carried out including regulation mechanism of functional oligosaccharide on animal bioactivity, oligosaccharide vaccine adjuvant, oligosaccharide lead compounds and the related products, controllable degradation, modification, separation, and clean preparation process for scale production.

Functional self-assembled vaccine

Schematic diagramof DSPE-PCB lipoplexes for siRNA delivery with enhanced siRNA endosomal/lysosomal escape ability

Liver section observed under confocal microscopy and In vivo functional study of lipoplexes in C57BL/6 mice

Collagen peptides coating microcarriers with controllable structure and the cell culture result (144 h)

4. Biomaterial formulat ions based on lipid molecules

Nano biomaterial systems with various structure and function were developed by using biocompatible lipid molecules. Effects of molecular structure on lipid material were investigated to reveal the relationship between changes of the structure on molecular level and the transport function of drug delivery system. They worked on the key scientific problems existing in the nano lipid system used as biomedical carrier and developed clinical formulations and scaled preparation process.

5. Preparation and application of functional protein and peptide

Proteins and peptide with high purity is the basis for modern biotechnology. The team broke through the key technology

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of preparing collagen peptide with controlled molecular weight and distribution by integrating enzyme degradation and membrane separation. They obtained collagen peptides with controllable sequence and charge density and used HPLC-MALLS or MALDI-TOF for product quality inspection. The above-mentioned biomaterial as health care products, nutrition, and microcarrier for animal cell culture achieved good application results.

Selected Publications and Achievements

National Science and Technology Award of China 2009, Second gradeA super macroporous polymeric microsphere and preparation process thereof, European Patentgranted, EP2088160, 2012.10.31Preparation of polysaccharide beads, American Patent granted, US8137563, 2012.2.29Xuehai Yan, Junbai Li, Helmuth Möhwald. Templating Assembly of Multifunctional Hybrid Colloidal Spheres, Adv. Mater. 24(2012): 2663-2667. (Frontispiece). IF: 13.877Zhanguo Yue, Wei Wei, Zuoxiang You, Qin zheng Yang, HuaYue, Zhiguo Su, Guanghui Ma. Iron Oxide Nanotube for Magnetically Guided Delivery and pH Activated-Release of Insoluble Anticancer Drugs. Adv. Funct. Mater., 21(18)(2011): 3446-3453. IF 10.342Weifeng Zhang, Lianyan Wang, Yuan Liu, Xiaoming Chen, Qi Liu, JileiJia, Tingyuan Yang, ShaohuiQiu, Guanghui Ma. Immune responses to vaccines involving a combined antigen-nanoparticle mixture and nanoparticle-encapsulated antigen formulation. Biomaterials 35 (2014) : 6086-6097. IF 8.496Wei Wei, Pi-Ping Lv, Xiao-Ming Chen, Zhan-GuoYue, Qiang Fu, Shi-Ying Liu, HuaYue, Guang-Hui Ma. Codelivery of mTERTsiRNA and paclitaxel by chitosan-based nanoparticles promoted synergistic tumor suppression. Biomaterials 34 (2013): 3912-3923. IF 8.496Shiying Liu, Wei Wei, Hua Yue, Dezhi Ni, Zhanguo Yue, Shuang Wang, Qiang Fu, Yueqi Wang, Guanghui Ma, Zhiguo Su. Nanoparticles-based multi-adjuvant whole cell tumor vaccine for cancer immunotherapy. Biomaterials. 34 (2013) : 8291-8300. IF 8.496Youbin Wu, Wei Wei, Meng Zhou, Yueqi Wang, Jie Wu, Guanghui Ma, Zhiguo Su. Thermal-sensitive hydrogel as adjuvant-free vaccine delivery system for H5N1 intranasal immunization. Biomaterials. 33(7)(2012): 2351-2360. IF 8.496Guanghui Ma, Zhiguo Su, “Microspheres and Microcapsules in Biotechnology - Design, Preparation and Applications”, Pan Stanford Publishing, 2013, Singapore

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Research Professors

Prof. Guanghui Ma (Team Leader), received her Bc.D from Gunma University (Japan) in 1988, Master degree and Ph.D. degree from Tokyo Institute of Technology (Japan) respectively in 1990 and 1993. Then, she joined in Tokyo University of Agriculture and Technology (Japan) as an assistant professor (1994-2001). She has been a professor of IPE since 2001, where she has been pointed as Deputy Director of IPE, CAS (2005-2013). Since 2012, she was pointed as the Director of National Key Laboratory of Biochemical Engineering. She was awarded the National Science and Technology Award of China (2009, Second grade, 39 in all of the fields of China). She obtained the Young Women Research Award 2009 (the first in Engineering and technology series) and YABEC Award for her invaluable contribution (2012) from Asian Foundation of Biotechnology (AFOB). Some other awards included New Century Women Invention Award of China 2008 (10 persons in all of the fields), Award for Women Innovation Research Group of Chinese Academy of Sciences 2008 (5 groups in all of the fields), Award for Best Ten Women Scientists of Chinese Academy of Sciences 2005, Award for Women Scientists from Central Government Agencies 2005, Winner of 100 Talents Plan of Chinese Academy of Sciences 2001, and Winner of Chinese Outstanding Young Scientists 2001 (around 3 persons in Chemical Engineering field).She has published more than 200 SCI articles in peer-reviewed scientific journals, such as JACS, Adv. Mater., Adv. Funct. Mater., Biomaterials, Nanomedicine, and J. Control. Release, J. Chromatogr. A, which have been cited overall more than 2700 times. 11 English scientific books and 16 academic book chapters also be published. More than 100 patents (42 granted) and 3 PCT were granted.

AffiliationEditorial Board member of J Microcapsulation (SCI)Editorial Board member of Frontier of Chemical Science and Engineering (Wiley)Editorial Board member of Encapsulation Adsorption Sciences (JEAS)Deputy director of Chinese Particle SocietyCommittee member of Japan Polymeric Microsphere Symposium (A conferences series) (only one person from aboard)

Research InterestsBioseparation media; Drug control release; Vaccine delivery system (adjuvant); Hydrogel for biodrug delivery;

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Prof. Yuguang Du was born in 1963 and received his M.Sc. degree in microbiology from Northwest Plateau Institute of Biology, CAS in 1990. He was Assistant Prof. at Northwest Plateau Institute of Biology, CAS (1990-1994) and Dalian Institute of Chemical Physics, CAS (1994-2002). He worked as a professor at Dalian institute of Chemical Physics, CAS (2002-2013), where he had been the Director of natural products and glucose engineering (1805) group. As a group leader, Prof. DU has been working in the Glyco-bioengineering Group of Institute of Process Engineering, CAS (2013-). He has been awarded:2000 DaBeiNong S&T Achievements2001, 2002 and 2006 LiaoNing Province S&T Progress Award (2 second prizes;1 third prize)2000, 2005 and 2007 Dalian S&T Progress Award(3 first prizes)2002 Dalian Excellent Inventor2003 LiaoNing Province Millions of Talents Engineering(hundred scale)2007 China Agricultural Science and Education Award(third prize)2008 China Society of Plant Protection S&T Award (second prize)He has published more than 210 papers in the academic journals, applied for nearly one hundred patents, and written 5 treatises in Chinese and English.

AffiliationVice-Chairman, Glyco-biotechnology Committee of Chinese biotechnology Society;Vice-Chairman, Chitin Committee of Chinese Chemical Society;Member, Glycoconjugates Committee of Chinese Biochemistry and Molecular Biology Society;Member, National Glycoengineering Research Center Academic Committee;Member, Feed Additive Committee and Judging member of National Feed of Chinese Feed Industry Association;

Research InterestsPlant glycobiology; Exploring the mechanisms of various oligosaccharides regulation plant development and immunity, especially revealing the role of O-GlcNAc signaling in plant defense; Focusing on new technologies on oligosaccharide analysis, separation and preparation, establishing a library of natural oligosaccharides; Developing new technologies on the oligosaccharide engineering, oligosaccharide health products, bio-pesticides, and feed additives.

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Prof. Xuehai Yan was born in 1979. He obtained his PhD with distinction in physical chemistry at the Institute of Chemistry, CAS in 2008. After that, he as a postdoctoral fellow moved to the Max Planck Institute of Colloids and Interfaces in Germany, where he won a research fellowship from the Alexander von Humboldt Foundation (2009-2011). In December 2012, he won the Talent Fund from the Recruitment Program of Global Youth Experts in China and took up the current position. He has published 35 papers, a book published by Wiley-VCH, a book chapter in Pan Stanford Publishing, and several patents authorized.

AffiliationMember, Committee of Youth Chemists, Chinese Chemical Society (2014-)

Research InterestsBiomolecular self-assembly and nanoengineering; drug Delivery; Biocatalysts and vaccine Adjuvants; Photodynamic Therapy; Biomimetic Protocells; Organized Chemistry.

Prof. Xin Zhang was born in 1979 and received her Ph.D. degree in life science from Strasbourg University in France in 2008. She has been a professor of IPE since 2010. She has published more than 30 papers, 2 co-authored monographs, and held 8 patents.

AffiliationEditor, Nanomedicine and Nanobiology (2012-)

Research InterestsBiomaterials; Drug delivery; Diagnostic imaging; DNA Vaccine adjuvant

Prof. Guifeng Zhang was born in 1972 and received his Ph.D. degree in Biochemical Engineering from Institute of Process Engineering in 2008. He has been a professor of IPE since 2012. He was awarded the first prize of science and technology awards of Shandong province (2011), technology innovation awards of China instrument and control society (2011), and the first prize of testing & analysis awards from the China association for instrumental analysis (2013). He has published more than 60 papers, 2 co-authored monographs, and held 6 patents.

AffiliationEditorial board member, Journal of Biology (2009-)Member, the Committee of experts of China Health Care Association (2011-)

Research Interests Preparation and application of protein-based biodegradable materials; Interaction between bio-molecule and of biomaterial surface; Application of MS in material science & engineering.