- Email: [email protected]
A model for facilitating translational research and development in China: Call for establishing a Hong Kong Branch of the Chinese National Engineering Research Centre for Biomaterials
Journal of Orthopaedic Translation (2014) 2, 170e176
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://ees.elsevier.com/jot
PERSPECTIVE
A model for facilitating translational research and development in China: Call for establishing a Hong Kong Branch of the Chinese National Engineering Research Centre for Biomaterials Liming Bian a, Arthur F.T. Mak a,**, Chi Wu b, Chunyiu Cheng c, Zhongwei Gu d, Xingdong Zhang d, Ling Qin c,* a Division of Biomedical Engineering, Department of Mechanical and Automation Engineering, Faculty of Engineering, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China b Department of Chemistry, Faculty of Sciences, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China c Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China d National Engineering Research Centre for Biomaterials, Sichuan University, Sichuan, People’s Republic of China
Received 2 July 2014; received in revised form 11 July 2014; accepted 11 July 2014
Available online 5 August 2014
KEYWORDS Research and development; biomaterials; clinical translation
Summary With significant improvements in living standards in China and the aging population that accompanies these improvements, the market demand for high-quality orthopaedic biomaterials for clinical applications is tremendous and growing rapidly. There are major efforts to promote cooperation between different scientific institutes with complementary strengths for the further development of the biomaterial industry in China to achieve the technological level of developed countries. An excellent example is that the Ministry of Science and Technology of the People’s Republic of China (MOST; Beijing, China) established the Chinese National Engineering Research Centres (CNERCs), which serve as a major initiative in driving basic and applied technological research and development (R&D) in mainland China. To create a win-win situation with Hong Kong, the MOST and the Hong Kong Innovation and Technology Commission are jointly establishing the Hong Kong Branch of the CNERCs. Through an amicable
* Corresponding author. Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China. ** Corresponding author. Division of Biomedical Engineering, Department of Mechanical and Automation Engineering, Faculty of Engineering, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China. E-mail addresses: [email protected] (A.F.T.Mak), [email protected] (L.Qin). http://dx.doi.org/10.1016/j.jot.2014.07.002 2214-031X/Copyright ª 2014, Chinese Speaking Orthopaedic Society. Published by Elsevier (Singapore) Pte Ltd. All rights reserved.
A model for facilitating translational research and development in China
171
arrangement, the Chinese University of Hong Kong (CUHK; Shatin, Hong Kong) and the Chinese National Engineering Research Centre for Biomaterials (i.e., Main Centre) in Chengdu, People’s Republic of China have decided to apply to establish the Hong Kong Branch of the CNERC for Biomaterials at the CUHK. The effort in establishing the Hong Kong Branch of Biomaterials seeks to promote further collaboration with the Main Centre with the goals of promoting synergy and a win-win cooperation between mainland China and Hong Kong in scientific research, talent cultivation, clinically driven novel biomaterials product design, and preclinical and clinical testing. It will thus become a model for the successful collaboration between the Hong Kong research institutions and the mainland CNERCs in the area of biomaterials. Such initiatives will facilitate close collaboration in translational medicine associated with biomaterial development and application. Copyright ª 2014, Chinese Speaking Orthopaedic Society. Published by Elsevier (Singapore) Pte Ltd. All rights reserved.
Background on the establishment of the Hong Kong Branch of the Chinese National Engineering Research Centres Chinese National Engineering Research Centres The Chinese National Engineering Research Centres (CNERCs) are under the auspices of the State Ministry of Science and Technology (MOST; Beijing, China) and serve as a major initiative in driving basic and applied technological research and development (R&D) in mainland China; there are more than 200 CNERCs in all major engineering areas in mainland China [1]. The CNERCs focus on providing engineering research and consultancy support to industries includes enhancing core competency on the transformation of technology achievements for productivity; promoting a higher level of maturity, compatibility, and engineering standards in technology results; and providing technological innovation support for national socioeconomic development [1].
Hong Kong Branch of the CNERCs In the autumn of 2011, vice-Premier Keqiang Li visited Hong Kong and announced the establishment of a Hong Kong Branch of the CNERCs [2]. The aim was to make the Hong Kong Branch a major element in the National Engineering Research Centre mechanism in which the Hong Kong Branch would fully utilise Hong Kong’s advantages in technological resources and realise a synergy of the respective strengths of Hong Kong and the mainland. This would enhance the capability in engineering and commercialisation, promote the technological advancement of mainland industries and the upgrading of Hong Kong’s industries, and enhance overall competitiveness [2]. The essential requirement for establishing the Hong Kong Branch is that there are already approved CNERCs on the mainland. To start with, Hong Kong Science Park was formally designated by the MOST of the People’s Republic of China as a National High-tech Industrialization (Partner) Base for Green Technology, whereas the Hong Kong Applied Science and Technology Research Institute (ASTRI; Shatin, Hong Kong) received
approval from the MOST in June 2013 to establish the Hong Kong Branch of the National Engineering Research Centre for Application-specific Integrated Circuit System in collaboration with the Southeast University in Nanjing (Nanjing, China) [3,4].
Formation of the Working Group to apply for the establishment of the Hong Kong Branch of CNERCs for Biomaterials Medical and socioeconomic demands With significant improvements in living standards in China and the aging population that accompanies these improvements, the number of patients with significant musculoskeletal disorders such as osteoporosis and osteoarthritis has been increasing rapidly. The resulting clinical or market demand for high-quality orthopaedic biomaterials for clinical applications is very substantial. According to official statistics, 100 million patients have osteoarthritis; as many as 300e400 million patients have tooth defects and tooth loss; 70 million patients have osteoporosis; nearly 10 million patients each year have bone defects caused by illness, accidents, and sports injuries; and tens of millions of people require craniofacial and breast cosmetic plastic surgeries [5,6]. The treatment of these diseases requires biomaterials, thus creating a huge market for the biomaterial industry. According to the statistics, the market value of the biotechnology industry, which includes biomaterials, had already exceeded 800 billion yuan in 2008 [7]. Biomaterials also have a very promising prospect in other clinical applications such as in the diagnosis and treatment of cardiovascular diseases, cancer, and other major diseases. Biomaterials are primarily used as medical devices in clinical applications in China and their products account for approximately 40e50% of the medical devices market [7]. Research and development, testing, and clinical translation of biomaterials as a high-value-added, technology-intensive, low energy consumption, pollution-free high-tech industry are very consistent with the direction of the future economy in mainland China and in Hong Kong. The
172
L. Bian et al.
establishment of the biomaterials industry will effectively promote the health of residents in mainland China and in Hong Kong, and greatly promote local economic development and the creation of high-tech jobs [2e4,8]. As early as the early 1980s, Professor Xingdong Zhang of the Sichuan University (Sichuan, China), who is also academician of the Chinese Academy of Engineering (Beijing, China) and fellow of the United States National Academy of Engineering (Washington, DC, USA), took the lead in China to develop nearly 20 series and 200 types of biomaterial implants for bone, teeth, soft tissue repair, and artificial hip joints. Professor Zhang and his group promoted the application of these biomaterial products in more than 600 hospitals. They also received good outcomes and six registration certificates from the State Food and Drug Administration. In 2000, the National Engineering Research Centre for Biomaterials was officially established and became the first open national biomaterials professional R&D institute with a focus on the development of functional biomaterial products and clinical translation [1,9].
indispensable role in the development and translation of biomaterials, and has led the technical development and clinical translation of orthopaedic biomaterials [8]. Through an amicable arrangement, the CUHK and the CNERC for Biomaterials have decided to establish the Hong Kong Branch of the CNERC for Biomaterials at CUHK. This effort in establishing the Hong Kong Branch of Biomaterials seeks to promote further collaboration with the Main Centre with the goals of promoting synergy and win-win cooperation between mainland China and Hong Kong in scientific research, talent cultivation, clinically driven novel biomaterials product design, and preclinical and clinical testing. It will thus become a model for the successful collaboration between the Hong Kong research institutions and the mainland CNERCs in the area of biomaterials (Fig. 1). The application for the Hong Kong Branch of CNERC for Biomaterials is built on the foundation of synergistic strengths and long-term collaboration. These are essential elements in translational medicine, especially in the R&D of orthopaedic materials, implants, and devices [12e19].
Formation of the Application Working Group
Missions of the Hong Kong Branch of Biomaterials
As early as 1996, Professor Zhang’s group began collaborating with the Department of Orthopaedics and Traumatology of the Chinese University of Hong Kong (CUHK; Shatin, Hong Kong) and the Department of Mechanical Engineering of the Hong Kong University of Sciences and Technology (HKUST; Clear Water Bay, Hong Kong) on developing translation research on hydroxyapatiteetricalcium phosphate-based scaffold implantable biomaterials for orthopaedic applications [10e12]. In May 2014, under the backdrop of this development, biomaterial researchers at the CUHKdwho were led by Professor Ling Qin of the Faculty of Medicine, Professor Arthur Mak of the Faculty of Engineering, and Professor Chi Wu of the Faculty of Sciencesdproposed to establish a multidisciplinary Hong Kong Branch of the National Engineering Research Centre for Biomaterials (hereafter referred to as the Hong Kong Branch for Biomaterials). As mentioned previously, the National Engineering Research Centre for Biomaterials (i.e., the Main Centre listed in the CNERCs) is the only National Engineering Research Centre that focuses on the R&D and translation of biomaterials for clinical applications. Professor Xingdong Zhang (the academic leader of the Centre) and Professor Zhongwei Gu (the Director of the Centre and the principal scientist of Program 973) are world-renowned experts in biomaterials. In China, Professor Zhang has been a pioneer in the research of bioactive ceramics and coatings. His group has developed a series of biomedical products for orthopaedic, dental, and other relevant medical applications. Their research demonstrated that inanimate calcium phosphate ceramics could induce bone formation, and established the prototype of biomaterial-induced bone induction theory. Professor Zhang is also a pioneer in expanding new ways for developing a new generation of biomaterials. Professor Gu has enjoyed worldwide recognition in the fields of polymerbased biomaterials research, controlled-release systems for drugs/bioactive substances, and nanobiomaterials. Since the Centre’s establishment in China, it has had an
Through a joint synergistic collaboration with the Main Centre, the Hong Kong Branch of Biomaterials will undertake the following missions to advance the engineering and enterprising of biomaterials in China, especially in Hong Kong. (1) To innovate biomaterials through their basic science and their engineering technology, as driven by clinical demands. (2) To develop new methods and models to explore the molecular markers for biocompatibility research and assessment of biomaterials. (3) To conduct preclinical and clinical testing of biomaterials and conduct the associated technology research for clinical applications. (4) To establish jointly with relevant enterprises a demonstrative base for enterprising biomaterials and for the clinical translation of their products. (5) To nurture jointly with relevant disciplines at the CUHK and Sichuan University, advanced professionals with integrative
Figure 1 Paradigm for the clinically driven development of biomaterials. CFDA Z China Food and Drug Administration.
A model for facilitating translational research and development in China competence in medicine and engineering, and thus offer postgraduate continuing education for professionals in the relevant industries. (6) To serve as a major window for national and global collaborations in related sciences and businesses for the purpose of academic exchanges, information mining, and consultative services.
Work of the Hong Kong Branch of Biomaterials Based on strength (e.g., manpower, infrastructure, track records), the Hong Kong Branch of Biomaterials will contribute in the following areas. (1) To propose the requirements on the design and standards of biomaterials and promote the clinical applications of mature products, based on clinical needs. (2) To establish the theoretical and experimental preclinical models and conduct clinical testing and evaluations. (3) To conduct basic research on the bioactivity and efficacy of biomaterials. (4) To develop novel bioactive and functional biomaterials. (5) To assist the development and improvement of preparing and processing technology of advanced biomaterials (which includes three-dimensional printing). (6) To explore the applications of biomaterials in stem cells, regenerative medicine, and rehabilitation medicine.
Scope of collaboration with the Main Centre The Hong Kong Branch of Biomaterials will effectively cooperate with the Main Centre in mainland China on the R&D of clinical needs-oriented advanced biomaterials, basic research on materials and biology, animal testing, and clinical testing. The specific cooperative measures include R&D, training, and clinical service (Fig. 1) are as follows. (1) To consolidate and develop in the areas of clinical applications (to further improve and establish indications for the clinical use of biomaterials). (2) To collaborate on programs (i.e. jointly complete the existing programs and jointly apply for new programs). (3) To share information and intellectual property (e.g., data obtained from animal
Figure 2
173
models and clinical testing on biomaterials, new technology, and new processes for preparation of biomaterials, and information of Phase III and Phase IV clinical trials). (4) To share resources (e.g., laboratory equipment, facilities, and medical samples). (5) To exchange talent and training (e.g., jointly educate postgraduates towards joint postgraduate program in biomaterials for medical applications, exchange and train R&D and management personnel). The Orthopaedic Learning Centre in CUHK of the applicant unit has a 15-year history in training orthopaedic surgeons and research scientists in AsianePacific region [20], which will provide training and education to exchange personnel from the Main Centre. (6) To collaborate with existing enterprises and incubate new businesses, promote effective cooperation and the development of medical platforms with industrial-academic research partnership. (7) To conduct clinical studies and evaluations. (8) To provide training and service for the marketed products. The potential contributions of the Hong Kong Branch of Biomaterials to R&D and the translation of biomaterials are summarized, as follows. (1) To improve and establish indications of new biomaterials in clinical uses. (2) To obtain data on the efficacy of biomaterials in tests with animal models and clinical applications and to optimize the products. The evaluation of biomaterials in the animal models and clinical applications is an essential step during clinical translation. The Hong Kong Branch of Biomaterials has substantial scientific experience, experimental equipment, and clinical resources in animal models and clinical testing of biomaterials [21e23]. The Hong Kong Branch of Biomaterials will provide important experimental data for existing and innovative biomaterials via testing in animal models and clinical testing, and thus will have a strong role in further optimal design and clinical translation of biomaterials. (3) To clarify the molecular mechanism of cell and tissue responses to biomaterials. Biomaterials are in close contact with human tissues and cells. The effects of biomaterials on tissues and cells at molecular level determine their normal functions in the human body. The Hong Kong Branch has a number of world-class scholars and
The management structure and functions of the Hong Kong Branch of Biomaterials. R&D Z research and development.
174
L. Bian et al.
Figure 3 The exchange mechanism between the Main Centre in the list of CNERCs in mainland China and the Hong Kong Branch of Biomaterials. CNERCs Z Chinese National Engineering Research Centres; Dept. Z department; R&D Z research and development.
experts in research studies related to molecular biology and cellular biology. The Hong Kong Branch of Biomaterials will make important contributions in revealing the molecular mechanism of actions of biomaterials on cells and tissues, and thereby effectively promote the optimal design of biomaterials and improve the effectiveness of biomaterials [24e26]. (4) To develop novel active and targeted biomaterials. The Hong Kong Branch has strong research strengths in materials science, particularly in the fields of design and preclinical and clinical validation of metallic materials and polymer materials for medical applications [24e32]. The Hong Kong Branch of Biomaterials will make important contributions to the development of innovative metallic biomaterials, polymer implant biomaterials, drug controlled-release materials and targeted delivery systems, and modification of bioactive molecules on biomaterials. (5) To develop advanced preparation and processing technology for biomaterials. The Hong Kong Branch of Biomaterials has long-term research experience, high-end research personnel, and complete research equipment in the preparation and processing technology for emerging biomaterials. The Hong Kong Branch will perform effective work in fields such as three-dimensional printing and surface coating technology biomaterials. (6) To study the applications of biomaterials in stem cells, regenerative medicine, and rehabilitation medicine, the Hong Kong Branch of Biomaterials will also focus on the development of novel biomaterials, stem cell carriers, transcutaneous implant materials, advanced exoskeleton materials, and other key technologies that have an important role in promoting the clinical applications of stem cells and novel rehabilitation biomaterials.
Management system and operation mechanism proposed for the Hong Kong Branch of Biomaterials Based on synergistic collaboration between medical expertise and engineering expertise, the administration
unit of the Hong Kong Branch of Biomaterials will be established at the Faculty of Medicine of the CUHK (Shatin, Hong Kong). Professor Ling Qin, who is director of the Musculoskeletal Research Laboratory in the Department of Orthopaedics and Traumatology of the CUHK, will assume the post as the director of the Hong Kong Branch. Professor Fuk-Tat Mak (director of the Biomedical Engineering Division of the CUHK) and Professor Chi Wu (who is a Wei Lun Professor of Chemistry at the Department of Chemistry of the CUHK) will serve as the codirectors of the Hong Kong Branch of Biomaterials. To achieve effective management and implementation of the overall project and tasks, the Hong Kong Branch will organize and coordinate the faculty members who are engaged in teaching and researching biomaterials from the Faculty of Medicine, the Faculty of Engineering, and the Faculty of Science at the CUHK to consolidate the existing interdisciplinary cooperation and further promote collaborative research with the Main Centre. Professor Qin, Professor Mak, and Professor Wu and the Working Group1 have proposed establishing a multicentre biomaterial research institute by integrating research strengths from the Faculty of Medicine, the Faculty of Engineering, and the Faculty of Science at the CUHK [24e26]. Professor Francis Chan, who is dean of the Faculty of Medicine at the CUHK, will be chairman of the
1 The Working Group members in the list in the proposal for the Hong Kong Branch of CNERC of Biomaterials are the following: The Faculty of Medicine of the Chinese University of Hong Kong (Shatin, Hong Kong): Professors Ling Qin (Director of the Hong Kong Branch), Chun-Yiu Cheng, Kai Ming Chan, Gang Li, Kwok-Sui Leung, Shekhar-Madhukar Kumta, and Wing-Hoi Cheung. Faculty of Engineering of the Chinese University of Hong Kong (Shatin, Hong Kong): Professors Arthur Mak (codirector of the Hong Kong Branch), Charlie Wang, Jonathan Choi, Li Zhang, Wei Hsin Liao, Liming Bian, and Douglas Yung. Faculty of Science of the Chinese University of Hong Kong: Professors Chi Wu [codirector of the Hong Kong Branch and academician of the Chinese Academy of Science (Beijing, China)], Michael Chan, and To Ngai.
A model for facilitating translational research and development in China
175
Figure 4 The diagram shows the complementation and cooperation between the Main Centre and the Hong Kong Branch of Biomaterials. R&D Z research and development.
Management Committee of Hong Kong Branch. Assuming the post as vice-chairmen are Professor Wong Ching Ping, who is Dean of the Faculty of Engineering and academician of the Chinese Academy of Engineering (Beijing, China) and the United States National Academy of Engineering, and Professor Henry Nai-Ching Wong, who is Dean of the Faculty of Science and academician of Chinese Academy of Sciences (Beijing, China). An advisory committee and an executive core group, which includes the responsible persons of the Main Centre, will be established. The management structures and the functions of the Main Centre of CNERC in mainland China and the Hong Kong Branch have been proposed (Fig. 2). The exchange mechanism between the Main Centre and its Hong Kong Branch is also listed for the synergistic running of bilateral collaboration (Fig. 3). Synergy should be built on a strong foundation of biomaterial research at the Main Centre and the Hong Kong Branch by the appropriate alignment of research directions (Fig. 4). The establishment of the Hong Kong Branch of Biomaterials will lead to the development of biomaterial industries in the region, which is consistent with the national strategic investment in new materials and biomedical technology. In summary, biomaterials and key technologies have made great progress in recent years in China. However, a large gap remains between the technical level of biomaterial products in China and internationally. Therefore, further development of the biomaterial industry in China is in urgent need of promoting cooperation between different
scientific institutes with complementary strengths. The National Engineering Research Centre for Biomaterials and the Hong Kong Branch of Biomaterials in CUHK jointly established by the Faculty of Medicine, Faculty of Engineering, and Faculty of Science of the CUHK will favourably complement each other. The establishment of the Hong Kong Branch of Biomaterials will further enhance the R&D level of biomaterials in China and promote translation and clinical applications of high-end biomaterials.
Conflicts of interest All authors declare no conflicts of interest.
Acknowledgements We thank Dr. Simon Chow for drawing Fig. 1 used in this article.
References [1] Ministry of Science and Technology of the People’s Republic of China [Internet; in Chinese]. www.most.gov.cn. [accessed 19.07.14]. [2] Ministry of Science and Technology of the People’s Republic of China [Internet; in Chinese]. National Engineering Research Center and National Key Laboratory of reporting subcenters in Hong Kong partner laboratory assessment briefing held in Hong
176
[3]
[4] [5]
[6] [7] [8]
[9] [10]
[11]
[12] [13] [14] [15]
[16] [17] [18]
L. Bian et al. Kong. http://www.most.gov.cn/kjbgz/201403/t20140312_ 112277.htm. [accessed 19.07.14]. University of Hong Kong [Internet]. Vice-Premier of the State Council Li Keqiang attends The University of Hong Kong Centenary Ceremony. http://www.hku.hk/press/news_detail_ 6552.html. [accessed 19.07.14]. http://www.astri.org/main/?contentnamespaceZnews_ room:press_releases:content:20120705ar. Choong P, Brooks P. Achievements during the bone and joint decade 2000e2010. Best Pract Res Clin Rheumatol 2012;26: 173e81. Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003;81:646e56. Overview of the Chinese biomaterial industry and market; 2012. http://wenku.baidu.com/view/5a513f1d10a6f524ccbf85c5. Festel G, Kreimeyer A, Oels U, Zedtwitz MV, editors. The chemical and pharmaceutical industry in China: opportunities and threats for foreign companies. Heidelberg, Germany: Springer; 2005. http://www.biomater.com; http://www.csbm.org.cn/en/ index.php?aZart&idZ5. Guo LH, Guo X, Qin L, Cheng J, Zhang XD. XRPD quantitative analysis of biomaterials based on calcium phosphate. In: Proceedings of the 20th Annual International Conference of the IEEE-EBMS 1998. Piscataway, NJ: IEEE Engineering in Medicine and Biology Society; 1998. p. 2893e6. Lu X, Leng Y, Zhang X, Xu J, Qin L, Chan CW. Comparative study of osteoconduction on micromachined and alkalitreated titanium alloy surfaces in vitro and in vivo. Biomaterials 2005;26:1793e801. Butler D. Translational research: crossing the valley of death. Nature 2008;453:840e2. Jacobs JJ. Translational research: whither the ORS? J Orthop Res 2008;26:737e40. Zerhouni EA. Translational and clinical science-time for a new vision. N Engl J Med 2005;353:1621e3. Dai KR, editor. Translational medicine in China: from idea to concept to implementation. Xian, China: Publishing House of the 4th Military University; 2012. Qin L, Tang TT, Xie XH, Hung LK. Orthopaedic translational research. Chin J Orthop 2009;29:87e9. Qin L. Translational medicine in orthopaedics. J Orthop Transl 2013;1:3e5. Dai K-R, Yang F, Gan Y-K. Development of translational medicine in China: foam or feast? J Orthop Transl 2013;1:6e10.
[19] Yuan Y, Lin D, Chen F, Liu C. Clinical translation of biomedical materials and the key factors towards product registration. J Orthop Transl 2014;2:49e55. [20] Chinese University of Hong Kong [Internet]. Department of Orthopaedics and Traumatology. Orthopedic Learning Centre. www.olc-cuhk.org/e/index.html. [accessed 19.07.14]. [21] Qin L, Genant HK, Griffith J, Leung KS, editors. Advanced bioimaging technologies in assessment of quality of bone and scaffold biomaterials. Heidelberg, Germany: Springer; 2007. [22] Leung KS, Qin YX, Cheung WH, Qin L, editors. A practical manual for musculoskeletal research. Singapore: World Scientific Publishing Company; 2008. [23] Qin L, editor. Orthopaedic medicine [in Chinese]. Beijing, China: People’s Medical Publishing House; 2013. [24] Bian L, Guvendiren M, Mauck RL, Burdick JA. Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis. Proc Natl Acad Sci U S A 2013;110:10117e22. [25] Yue Y, Jin F, Deng R, Cai J, Dai Z, Lin MC, et al. Revisit complexation between DNA and polyethylenimine-effect of length of free polycationic chains on gene transfection. J Control Release 2011;152:143e51. [26] Zhang G, Guo B, Wu H, Tang T, Zhang BT, Zheng L, et al. A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nat Med 2012;18:307e14. [27] Xu L, Li G. Circulating mesenchymal stem cells and their clinical implications. J Orthop Transl 2014;2:1e7. [28] Tang J, Wang J, Xie X, Zhang P, Lai Y, Li Y, et al. Surface coating reduces degradation rate of magnesium alloy developed for orthopaedic applications. J Orthop Transl 2013;1: 41e8. [29] Gu XN, Xie XH, Li N, Zheng YF, Qin L. In vitro and in vivo studies on a Mg-Sr binary alloy system developed as a new kind of biodegradable metal. Acta Biomater 2012;8:2360e74. [30] Wang YB, Xie XH, Li HF, Wang XL, Zhao MZ, Zhang EW, et al. Biodegradable CaMgZn bulk metallic glass for potential skeletal application. Acta Biomater 2011;7:3196e208. [31] Li HF, Xie XH, Zhao K, Wang YB, Zheng YF, Wang WH, et al. In vitro and in vivo studies on biodegradable CaMgZnSrYb highentropy bulk metallic glass. Acta Biomater 2013;9:8561e73. [32] Chen SH, Zheng LZ, Xie XH, Wang XL, Lai YX, Chen SK, et al. Comparative study of poly (lactic-co-glycolic acid)/tricalcium phosphate scaffolds incorporated or coated with osteogenic growth factors for enhancement of bone regeneration. J Orthop Transl 2014;2:91e104.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://ees.elsevier.com/jot
PERSPECTIVE
A model for facilitating translational research and development in China: Call for establishing a Hong Kong Branch of the Chinese National Engineering Research Centre for Biomaterials Liming Bian a, Arthur F.T. Mak a,**, Chi Wu b, Chunyiu Cheng c, Zhongwei Gu d, Xingdong Zhang d, Ling Qin c,* a Division of Biomedical Engineering, Department of Mechanical and Automation Engineering, Faculty of Engineering, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China b Department of Chemistry, Faculty of Sciences, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China c Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China d National Engineering Research Centre for Biomaterials, Sichuan University, Sichuan, People’s Republic of China
Received 2 July 2014; received in revised form 11 July 2014; accepted 11 July 2014
Available online 5 August 2014
KEYWORDS Research and development; biomaterials; clinical translation
Summary With significant improvements in living standards in China and the aging population that accompanies these improvements, the market demand for high-quality orthopaedic biomaterials for clinical applications is tremendous and growing rapidly. There are major efforts to promote cooperation between different scientific institutes with complementary strengths for the further development of the biomaterial industry in China to achieve the technological level of developed countries. An excellent example is that the Ministry of Science and Technology of the People’s Republic of China (MOST; Beijing, China) established the Chinese National Engineering Research Centres (CNERCs), which serve as a major initiative in driving basic and applied technological research and development (R&D) in mainland China. To create a win-win situation with Hong Kong, the MOST and the Hong Kong Innovation and Technology Commission are jointly establishing the Hong Kong Branch of the CNERCs. Through an amicable
* Corresponding author. Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China. ** Corresponding author. Division of Biomedical Engineering, Department of Mechanical and Automation Engineering, Faculty of Engineering, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China. E-mail addresses: [email protected] (A.F.T.Mak), [email protected] (L.Qin). http://dx.doi.org/10.1016/j.jot.2014.07.002 2214-031X/Copyright ª 2014, Chinese Speaking Orthopaedic Society. Published by Elsevier (Singapore) Pte Ltd. All rights reserved.
A model for facilitating translational research and development in China
171
arrangement, the Chinese University of Hong Kong (CUHK; Shatin, Hong Kong) and the Chinese National Engineering Research Centre for Biomaterials (i.e., Main Centre) in Chengdu, People’s Republic of China have decided to apply to establish the Hong Kong Branch of the CNERC for Biomaterials at the CUHK. The effort in establishing the Hong Kong Branch of Biomaterials seeks to promote further collaboration with the Main Centre with the goals of promoting synergy and a win-win cooperation between mainland China and Hong Kong in scientific research, talent cultivation, clinically driven novel biomaterials product design, and preclinical and clinical testing. It will thus become a model for the successful collaboration between the Hong Kong research institutions and the mainland CNERCs in the area of biomaterials. Such initiatives will facilitate close collaboration in translational medicine associated with biomaterial development and application. Copyright ª 2014, Chinese Speaking Orthopaedic Society. Published by Elsevier (Singapore) Pte Ltd. All rights reserved.
Background on the establishment of the Hong Kong Branch of the Chinese National Engineering Research Centres Chinese National Engineering Research Centres The Chinese National Engineering Research Centres (CNERCs) are under the auspices of the State Ministry of Science and Technology (MOST; Beijing, China) and serve as a major initiative in driving basic and applied technological research and development (R&D) in mainland China; there are more than 200 CNERCs in all major engineering areas in mainland China [1]. The CNERCs focus on providing engineering research and consultancy support to industries includes enhancing core competency on the transformation of technology achievements for productivity; promoting a higher level of maturity, compatibility, and engineering standards in technology results; and providing technological innovation support for national socioeconomic development [1].
Hong Kong Branch of the CNERCs In the autumn of 2011, vice-Premier Keqiang Li visited Hong Kong and announced the establishment of a Hong Kong Branch of the CNERCs [2]. The aim was to make the Hong Kong Branch a major element in the National Engineering Research Centre mechanism in which the Hong Kong Branch would fully utilise Hong Kong’s advantages in technological resources and realise a synergy of the respective strengths of Hong Kong and the mainland. This would enhance the capability in engineering and commercialisation, promote the technological advancement of mainland industries and the upgrading of Hong Kong’s industries, and enhance overall competitiveness [2]. The essential requirement for establishing the Hong Kong Branch is that there are already approved CNERCs on the mainland. To start with, Hong Kong Science Park was formally designated by the MOST of the People’s Republic of China as a National High-tech Industrialization (Partner) Base for Green Technology, whereas the Hong Kong Applied Science and Technology Research Institute (ASTRI; Shatin, Hong Kong) received
approval from the MOST in June 2013 to establish the Hong Kong Branch of the National Engineering Research Centre for Application-specific Integrated Circuit System in collaboration with the Southeast University in Nanjing (Nanjing, China) [3,4].
Formation of the Working Group to apply for the establishment of the Hong Kong Branch of CNERCs for Biomaterials Medical and socioeconomic demands With significant improvements in living standards in China and the aging population that accompanies these improvements, the number of patients with significant musculoskeletal disorders such as osteoporosis and osteoarthritis has been increasing rapidly. The resulting clinical or market demand for high-quality orthopaedic biomaterials for clinical applications is very substantial. According to official statistics, 100 million patients have osteoarthritis; as many as 300e400 million patients have tooth defects and tooth loss; 70 million patients have osteoporosis; nearly 10 million patients each year have bone defects caused by illness, accidents, and sports injuries; and tens of millions of people require craniofacial and breast cosmetic plastic surgeries [5,6]. The treatment of these diseases requires biomaterials, thus creating a huge market for the biomaterial industry. According to the statistics, the market value of the biotechnology industry, which includes biomaterials, had already exceeded 800 billion yuan in 2008 [7]. Biomaterials also have a very promising prospect in other clinical applications such as in the diagnosis and treatment of cardiovascular diseases, cancer, and other major diseases. Biomaterials are primarily used as medical devices in clinical applications in China and their products account for approximately 40e50% of the medical devices market [7]. Research and development, testing, and clinical translation of biomaterials as a high-value-added, technology-intensive, low energy consumption, pollution-free high-tech industry are very consistent with the direction of the future economy in mainland China and in Hong Kong. The
172
L. Bian et al.
establishment of the biomaterials industry will effectively promote the health of residents in mainland China and in Hong Kong, and greatly promote local economic development and the creation of high-tech jobs [2e4,8]. As early as the early 1980s, Professor Xingdong Zhang of the Sichuan University (Sichuan, China), who is also academician of the Chinese Academy of Engineering (Beijing, China) and fellow of the United States National Academy of Engineering (Washington, DC, USA), took the lead in China to develop nearly 20 series and 200 types of biomaterial implants for bone, teeth, soft tissue repair, and artificial hip joints. Professor Zhang and his group promoted the application of these biomaterial products in more than 600 hospitals. They also received good outcomes and six registration certificates from the State Food and Drug Administration. In 2000, the National Engineering Research Centre for Biomaterials was officially established and became the first open national biomaterials professional R&D institute with a focus on the development of functional biomaterial products and clinical translation [1,9].
indispensable role in the development and translation of biomaterials, and has led the technical development and clinical translation of orthopaedic biomaterials [8]. Through an amicable arrangement, the CUHK and the CNERC for Biomaterials have decided to establish the Hong Kong Branch of the CNERC for Biomaterials at CUHK. This effort in establishing the Hong Kong Branch of Biomaterials seeks to promote further collaboration with the Main Centre with the goals of promoting synergy and win-win cooperation between mainland China and Hong Kong in scientific research, talent cultivation, clinically driven novel biomaterials product design, and preclinical and clinical testing. It will thus become a model for the successful collaboration between the Hong Kong research institutions and the mainland CNERCs in the area of biomaterials (Fig. 1). The application for the Hong Kong Branch of CNERC for Biomaterials is built on the foundation of synergistic strengths and long-term collaboration. These are essential elements in translational medicine, especially in the R&D of orthopaedic materials, implants, and devices [12e19].
Formation of the Application Working Group
Missions of the Hong Kong Branch of Biomaterials
As early as 1996, Professor Zhang’s group began collaborating with the Department of Orthopaedics and Traumatology of the Chinese University of Hong Kong (CUHK; Shatin, Hong Kong) and the Department of Mechanical Engineering of the Hong Kong University of Sciences and Technology (HKUST; Clear Water Bay, Hong Kong) on developing translation research on hydroxyapatiteetricalcium phosphate-based scaffold implantable biomaterials for orthopaedic applications [10e12]. In May 2014, under the backdrop of this development, biomaterial researchers at the CUHKdwho were led by Professor Ling Qin of the Faculty of Medicine, Professor Arthur Mak of the Faculty of Engineering, and Professor Chi Wu of the Faculty of Sciencesdproposed to establish a multidisciplinary Hong Kong Branch of the National Engineering Research Centre for Biomaterials (hereafter referred to as the Hong Kong Branch for Biomaterials). As mentioned previously, the National Engineering Research Centre for Biomaterials (i.e., the Main Centre listed in the CNERCs) is the only National Engineering Research Centre that focuses on the R&D and translation of biomaterials for clinical applications. Professor Xingdong Zhang (the academic leader of the Centre) and Professor Zhongwei Gu (the Director of the Centre and the principal scientist of Program 973) are world-renowned experts in biomaterials. In China, Professor Zhang has been a pioneer in the research of bioactive ceramics and coatings. His group has developed a series of biomedical products for orthopaedic, dental, and other relevant medical applications. Their research demonstrated that inanimate calcium phosphate ceramics could induce bone formation, and established the prototype of biomaterial-induced bone induction theory. Professor Zhang is also a pioneer in expanding new ways for developing a new generation of biomaterials. Professor Gu has enjoyed worldwide recognition in the fields of polymerbased biomaterials research, controlled-release systems for drugs/bioactive substances, and nanobiomaterials. Since the Centre’s establishment in China, it has had an
Through a joint synergistic collaboration with the Main Centre, the Hong Kong Branch of Biomaterials will undertake the following missions to advance the engineering and enterprising of biomaterials in China, especially in Hong Kong. (1) To innovate biomaterials through their basic science and their engineering technology, as driven by clinical demands. (2) To develop new methods and models to explore the molecular markers for biocompatibility research and assessment of biomaterials. (3) To conduct preclinical and clinical testing of biomaterials and conduct the associated technology research for clinical applications. (4) To establish jointly with relevant enterprises a demonstrative base for enterprising biomaterials and for the clinical translation of their products. (5) To nurture jointly with relevant disciplines at the CUHK and Sichuan University, advanced professionals with integrative
Figure 1 Paradigm for the clinically driven development of biomaterials. CFDA Z China Food and Drug Administration.
A model for facilitating translational research and development in China competence in medicine and engineering, and thus offer postgraduate continuing education for professionals in the relevant industries. (6) To serve as a major window for national and global collaborations in related sciences and businesses for the purpose of academic exchanges, information mining, and consultative services.
Work of the Hong Kong Branch of Biomaterials Based on strength (e.g., manpower, infrastructure, track records), the Hong Kong Branch of Biomaterials will contribute in the following areas. (1) To propose the requirements on the design and standards of biomaterials and promote the clinical applications of mature products, based on clinical needs. (2) To establish the theoretical and experimental preclinical models and conduct clinical testing and evaluations. (3) To conduct basic research on the bioactivity and efficacy of biomaterials. (4) To develop novel bioactive and functional biomaterials. (5) To assist the development and improvement of preparing and processing technology of advanced biomaterials (which includes three-dimensional printing). (6) To explore the applications of biomaterials in stem cells, regenerative medicine, and rehabilitation medicine.
Scope of collaboration with the Main Centre The Hong Kong Branch of Biomaterials will effectively cooperate with the Main Centre in mainland China on the R&D of clinical needs-oriented advanced biomaterials, basic research on materials and biology, animal testing, and clinical testing. The specific cooperative measures include R&D, training, and clinical service (Fig. 1) are as follows. (1) To consolidate and develop in the areas of clinical applications (to further improve and establish indications for the clinical use of biomaterials). (2) To collaborate on programs (i.e. jointly complete the existing programs and jointly apply for new programs). (3) To share information and intellectual property (e.g., data obtained from animal
Figure 2
173
models and clinical testing on biomaterials, new technology, and new processes for preparation of biomaterials, and information of Phase III and Phase IV clinical trials). (4) To share resources (e.g., laboratory equipment, facilities, and medical samples). (5) To exchange talent and training (e.g., jointly educate postgraduates towards joint postgraduate program in biomaterials for medical applications, exchange and train R&D and management personnel). The Orthopaedic Learning Centre in CUHK of the applicant unit has a 15-year history in training orthopaedic surgeons and research scientists in AsianePacific region [20], which will provide training and education to exchange personnel from the Main Centre. (6) To collaborate with existing enterprises and incubate new businesses, promote effective cooperation and the development of medical platforms with industrial-academic research partnership. (7) To conduct clinical studies and evaluations. (8) To provide training and service for the marketed products. The potential contributions of the Hong Kong Branch of Biomaterials to R&D and the translation of biomaterials are summarized, as follows. (1) To improve and establish indications of new biomaterials in clinical uses. (2) To obtain data on the efficacy of biomaterials in tests with animal models and clinical applications and to optimize the products. The evaluation of biomaterials in the animal models and clinical applications is an essential step during clinical translation. The Hong Kong Branch of Biomaterials has substantial scientific experience, experimental equipment, and clinical resources in animal models and clinical testing of biomaterials [21e23]. The Hong Kong Branch of Biomaterials will provide important experimental data for existing and innovative biomaterials via testing in animal models and clinical testing, and thus will have a strong role in further optimal design and clinical translation of biomaterials. (3) To clarify the molecular mechanism of cell and tissue responses to biomaterials. Biomaterials are in close contact with human tissues and cells. The effects of biomaterials on tissues and cells at molecular level determine their normal functions in the human body. The Hong Kong Branch has a number of world-class scholars and
The management structure and functions of the Hong Kong Branch of Biomaterials. R&D Z research and development.
174
L. Bian et al.
Figure 3 The exchange mechanism between the Main Centre in the list of CNERCs in mainland China and the Hong Kong Branch of Biomaterials. CNERCs Z Chinese National Engineering Research Centres; Dept. Z department; R&D Z research and development.
experts in research studies related to molecular biology and cellular biology. The Hong Kong Branch of Biomaterials will make important contributions in revealing the molecular mechanism of actions of biomaterials on cells and tissues, and thereby effectively promote the optimal design of biomaterials and improve the effectiveness of biomaterials [24e26]. (4) To develop novel active and targeted biomaterials. The Hong Kong Branch has strong research strengths in materials science, particularly in the fields of design and preclinical and clinical validation of metallic materials and polymer materials for medical applications [24e32]. The Hong Kong Branch of Biomaterials will make important contributions to the development of innovative metallic biomaterials, polymer implant biomaterials, drug controlled-release materials and targeted delivery systems, and modification of bioactive molecules on biomaterials. (5) To develop advanced preparation and processing technology for biomaterials. The Hong Kong Branch of Biomaterials has long-term research experience, high-end research personnel, and complete research equipment in the preparation and processing technology for emerging biomaterials. The Hong Kong Branch will perform effective work in fields such as three-dimensional printing and surface coating technology biomaterials. (6) To study the applications of biomaterials in stem cells, regenerative medicine, and rehabilitation medicine, the Hong Kong Branch of Biomaterials will also focus on the development of novel biomaterials, stem cell carriers, transcutaneous implant materials, advanced exoskeleton materials, and other key technologies that have an important role in promoting the clinical applications of stem cells and novel rehabilitation biomaterials.
Management system and operation mechanism proposed for the Hong Kong Branch of Biomaterials Based on synergistic collaboration between medical expertise and engineering expertise, the administration
unit of the Hong Kong Branch of Biomaterials will be established at the Faculty of Medicine of the CUHK (Shatin, Hong Kong). Professor Ling Qin, who is director of the Musculoskeletal Research Laboratory in the Department of Orthopaedics and Traumatology of the CUHK, will assume the post as the director of the Hong Kong Branch. Professor Fuk-Tat Mak (director of the Biomedical Engineering Division of the CUHK) and Professor Chi Wu (who is a Wei Lun Professor of Chemistry at the Department of Chemistry of the CUHK) will serve as the codirectors of the Hong Kong Branch of Biomaterials. To achieve effective management and implementation of the overall project and tasks, the Hong Kong Branch will organize and coordinate the faculty members who are engaged in teaching and researching biomaterials from the Faculty of Medicine, the Faculty of Engineering, and the Faculty of Science at the CUHK to consolidate the existing interdisciplinary cooperation and further promote collaborative research with the Main Centre. Professor Qin, Professor Mak, and Professor Wu and the Working Group1 have proposed establishing a multicentre biomaterial research institute by integrating research strengths from the Faculty of Medicine, the Faculty of Engineering, and the Faculty of Science at the CUHK [24e26]. Professor Francis Chan, who is dean of the Faculty of Medicine at the CUHK, will be chairman of the
1 The Working Group members in the list in the proposal for the Hong Kong Branch of CNERC of Biomaterials are the following: The Faculty of Medicine of the Chinese University of Hong Kong (Shatin, Hong Kong): Professors Ling Qin (Director of the Hong Kong Branch), Chun-Yiu Cheng, Kai Ming Chan, Gang Li, Kwok-Sui Leung, Shekhar-Madhukar Kumta, and Wing-Hoi Cheung. Faculty of Engineering of the Chinese University of Hong Kong (Shatin, Hong Kong): Professors Arthur Mak (codirector of the Hong Kong Branch), Charlie Wang, Jonathan Choi, Li Zhang, Wei Hsin Liao, Liming Bian, and Douglas Yung. Faculty of Science of the Chinese University of Hong Kong: Professors Chi Wu [codirector of the Hong Kong Branch and academician of the Chinese Academy of Science (Beijing, China)], Michael Chan, and To Ngai.
A model for facilitating translational research and development in China
175
Figure 4 The diagram shows the complementation and cooperation between the Main Centre and the Hong Kong Branch of Biomaterials. R&D Z research and development.
Management Committee of Hong Kong Branch. Assuming the post as vice-chairmen are Professor Wong Ching Ping, who is Dean of the Faculty of Engineering and academician of the Chinese Academy of Engineering (Beijing, China) and the United States National Academy of Engineering, and Professor Henry Nai-Ching Wong, who is Dean of the Faculty of Science and academician of Chinese Academy of Sciences (Beijing, China). An advisory committee and an executive core group, which includes the responsible persons of the Main Centre, will be established. The management structures and the functions of the Main Centre of CNERC in mainland China and the Hong Kong Branch have been proposed (Fig. 2). The exchange mechanism between the Main Centre and its Hong Kong Branch is also listed for the synergistic running of bilateral collaboration (Fig. 3). Synergy should be built on a strong foundation of biomaterial research at the Main Centre and the Hong Kong Branch by the appropriate alignment of research directions (Fig. 4). The establishment of the Hong Kong Branch of Biomaterials will lead to the development of biomaterial industries in the region, which is consistent with the national strategic investment in new materials and biomedical technology. In summary, biomaterials and key technologies have made great progress in recent years in China. However, a large gap remains between the technical level of biomaterial products in China and internationally. Therefore, further development of the biomaterial industry in China is in urgent need of promoting cooperation between different
scientific institutes with complementary strengths. The National Engineering Research Centre for Biomaterials and the Hong Kong Branch of Biomaterials in CUHK jointly established by the Faculty of Medicine, Faculty of Engineering, and Faculty of Science of the CUHK will favourably complement each other. The establishment of the Hong Kong Branch of Biomaterials will further enhance the R&D level of biomaterials in China and promote translation and clinical applications of high-end biomaterials.
Conflicts of interest All authors declare no conflicts of interest.
Acknowledgements We thank Dr. Simon Chow for drawing Fig. 1 used in this article.
References [1] Ministry of Science and Technology of the People’s Republic of China [Internet; in Chinese]. www.most.gov.cn. [accessed 19.07.14]. [2] Ministry of Science and Technology of the People’s Republic of China [Internet; in Chinese]. National Engineering Research Center and National Key Laboratory of reporting subcenters in Hong Kong partner laboratory assessment briefing held in Hong
176
[3]
[4] [5]
[6] [7] [8]
[9] [10]
[11]
[12] [13] [14] [15]
[16] [17] [18]
L. Bian et al. Kong. http://www.most.gov.cn/kjbgz/201403/t20140312_ 112277.htm. [accessed 19.07.14]. University of Hong Kong [Internet]. Vice-Premier of the State Council Li Keqiang attends The University of Hong Kong Centenary Ceremony. http://www.hku.hk/press/news_detail_ 6552.html. [accessed 19.07.14]. http://www.astri.org/main/?contentnamespaceZnews_ room:press_releases:content:20120705ar. Choong P, Brooks P. Achievements during the bone and joint decade 2000e2010. Best Pract Res Clin Rheumatol 2012;26: 173e81. Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003;81:646e56. Overview of the Chinese biomaterial industry and market; 2012. http://wenku.baidu.com/view/5a513f1d10a6f524ccbf85c5. Festel G, Kreimeyer A, Oels U, Zedtwitz MV, editors. The chemical and pharmaceutical industry in China: opportunities and threats for foreign companies. Heidelberg, Germany: Springer; 2005. http://www.biomater.com; http://www.csbm.org.cn/en/ index.php?aZart&idZ5. Guo LH, Guo X, Qin L, Cheng J, Zhang XD. XRPD quantitative analysis of biomaterials based on calcium phosphate. In: Proceedings of the 20th Annual International Conference of the IEEE-EBMS 1998. Piscataway, NJ: IEEE Engineering in Medicine and Biology Society; 1998. p. 2893e6. Lu X, Leng Y, Zhang X, Xu J, Qin L, Chan CW. Comparative study of osteoconduction on micromachined and alkalitreated titanium alloy surfaces in vitro and in vivo. Biomaterials 2005;26:1793e801. Butler D. Translational research: crossing the valley of death. Nature 2008;453:840e2. Jacobs JJ. Translational research: whither the ORS? J Orthop Res 2008;26:737e40. Zerhouni EA. Translational and clinical science-time for a new vision. N Engl J Med 2005;353:1621e3. Dai KR, editor. Translational medicine in China: from idea to concept to implementation. Xian, China: Publishing House of the 4th Military University; 2012. Qin L, Tang TT, Xie XH, Hung LK. Orthopaedic translational research. Chin J Orthop 2009;29:87e9. Qin L. Translational medicine in orthopaedics. J Orthop Transl 2013;1:3e5. Dai K-R, Yang F, Gan Y-K. Development of translational medicine in China: foam or feast? J Orthop Transl 2013;1:6e10.
[19] Yuan Y, Lin D, Chen F, Liu C. Clinical translation of biomedical materials and the key factors towards product registration. J Orthop Transl 2014;2:49e55. [20] Chinese University of Hong Kong [Internet]. Department of Orthopaedics and Traumatology. Orthopedic Learning Centre. www.olc-cuhk.org/e/index.html. [accessed 19.07.14]. [21] Qin L, Genant HK, Griffith J, Leung KS, editors. Advanced bioimaging technologies in assessment of quality of bone and scaffold biomaterials. Heidelberg, Germany: Springer; 2007. [22] Leung KS, Qin YX, Cheung WH, Qin L, editors. A practical manual for musculoskeletal research. Singapore: World Scientific Publishing Company; 2008. [23] Qin L, editor. Orthopaedic medicine [in Chinese]. Beijing, China: People’s Medical Publishing House; 2013. [24] Bian L, Guvendiren M, Mauck RL, Burdick JA. Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis. Proc Natl Acad Sci U S A 2013;110:10117e22. [25] Yue Y, Jin F, Deng R, Cai J, Dai Z, Lin MC, et al. Revisit complexation between DNA and polyethylenimine-effect of length of free polycationic chains on gene transfection. J Control Release 2011;152:143e51. [26] Zhang G, Guo B, Wu H, Tang T, Zhang BT, Zheng L, et al. A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nat Med 2012;18:307e14. [27] Xu L, Li G. Circulating mesenchymal stem cells and their clinical implications. J Orthop Transl 2014;2:1e7. [28] Tang J, Wang J, Xie X, Zhang P, Lai Y, Li Y, et al. Surface coating reduces degradation rate of magnesium alloy developed for orthopaedic applications. J Orthop Transl 2013;1: 41e8. [29] Gu XN, Xie XH, Li N, Zheng YF, Qin L. In vitro and in vivo studies on a Mg-Sr binary alloy system developed as a new kind of biodegradable metal. Acta Biomater 2012;8:2360e74. [30] Wang YB, Xie XH, Li HF, Wang XL, Zhao MZ, Zhang EW, et al. Biodegradable CaMgZn bulk metallic glass for potential skeletal application. Acta Biomater 2011;7:3196e208. [31] Li HF, Xie XH, Zhao K, Wang YB, Zheng YF, Wang WH, et al. In vitro and in vivo studies on biodegradable CaMgZnSrYb highentropy bulk metallic glass. Acta Biomater 2013;9:8561e73. [32] Chen SH, Zheng LZ, Xie XH, Wang XL, Lai YX, Chen SK, et al. Comparative study of poly (lactic-co-glycolic acid)/tricalcium phosphate scaffolds incorporated or coated with osteogenic growth factors for enhancement of bone regeneration. J Orthop Transl 2014;2:91e104.