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 translationalresearch and development in China: Call forestablishing a Hong Kong Branch of theChinese National Engineering ResearchCentre 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 Chinab Department of Chemistry, Faculty of Sciences, Chinese University of Hong Kong, Hong Kong SAR,People’s Republic of Chinac Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology,Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of Chinad 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 2014Available online 5 August 2014

KEYWORDSResearch anddevelopment;

biomaterials;clinical translation

* Corresponding author. MusculoskeChinese University of Hong Kong, Hon** Corresponding author. Division ofneering, Chinese University of Hong K

E-mail addresses: arthurmak@cuhk

http://dx.doi.org/10.1016/j.jot.20142214-031X/Copyright ª 2014, The Autlicense (http://creativecommons.org/

Summary With significant improvements in living standards in China and the aging popula-tion that accompanies these improvements, the market demand for high-quality orthopaedicbiomaterials for clinical applications is tremendous and growing rapidly. There are major ef-forts to promote cooperation between different scientific institutes with complementarystrengths for the further development of the biomaterial industry in China to achieve the tech-nological level of developed countries. An excellent example is that the Ministry of Science andTechnology of the People’s Republic of China (MOST; Beijing, China) established the ChineseNational Engineering Research Centres (CNERCs), which serve as a major initiative in drivingbasic and applied technological research and development (R&D) in mainland China. To createa win-win situation with Hong Kong, the MOST and the Hong Kong Innovation and TechnologyCommission are jointly establishing the Hong Kong Branch of the CNERCs. Through an amicable

letal Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine,g Kong SAR, People’s Republic of China.Biomedical Engineering, Department of Mechanical and Automation Engineering, Faculty of Engi-ong, Hong Kong SAR, People’s Republic of China..edu.hk (A.F.T.Mak), Lingqin@cuhk.edu.hk (L.Qin).

.07.002hors. Published by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-NDlicenses/by-nc-nd/4.0/).

A model for facilitating translational research and development in China 171

arrangement, the Chinese University of Hong Kong (CUHK; Shatin, Hong Kong) and the ChineseNational Engineering Research Centre for Biomaterials (i.e., Main Centre) in Chengdu, People’sRepublic of China have decided to apply to establish the Hong Kong Branch of the CNERC forBiomaterials at the CUHK. The effort in establishing the Hong Kong Branch of Biomaterialsseeks to promote further collaboration with the Main Centre with the goals of promoting syn-ergy 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 clin-ical testing. It will thus become a model for the successful collaboration between the HongKong research institutions and the mainland CNERCs in the area of biomaterials. Such initia-tives will facilitate close collaboration in translational medicine associated with biomaterialdevelopment and application.Copyrightª 2014, The Authors. Published by Elsevier (Singapore) Pte Ltd. This is an open accessarticle under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background on the establishment of the HongKong Branch of the Chinese NationalEngineering Research Centres

Chinese National Engineering Research Centres

The Chinese National Engineering Research Centres(CNERCs) are under the auspices of the State Ministry ofScience and Technology (MOST; Beijing, China) and serve asa major initiative in driving basic and applied technologicalresearch and development (R&D) in mainland China; thereare more than 200 CNERCs in all major engineering areas inmainland China [1]. The CNERCs focus on providing engi-neering research and consultancy support to industries in-cludes enhancing core competency on the transformationof technology achievements for productivity; promoting ahigher level of maturity, compatibility, and engineeringstandards in technology results; and providing technolog-ical innovation support for national socioeconomic devel-opment [1].

Hong Kong Branch of the CNERCs

In the autumn of 2011, vice-Premier Keqiang Li visited HongKong and announced the establishment of a Hong KongBranch of the CNERCs [2]. The aim was to make the HongKong Branch a major element in the National EngineeringResearch Centre mechanism in which the Hong Kong Branchwould fully utilise Hong Kong’s advantages in technologicalresources and realise a synergy of the respective strengthsof Hong Kong and the mainland. This would enhance thecapability in engineering and commercialisation, promotethe technological advancement of mainland industries andthe upgrading of Hong Kong’s industries, and enhanceoverall competitiveness [2]. The essential requirement forestablishing the Hong Kong Branch is that there are alreadyapproved CNERCs on the mainland. To start with, HongKong Science Park was formally designated by the MOST ofthe People’s Republic of China as a National High-techIndustrialization (Partner) Base for Green Technology,whereas the Hong Kong Applied Science and TechnologyResearch Institute (ASTRI; Shatin, Hong Kong) received

approval from the MOST in June 2013 to establish the HongKong Branch of the National Engineering Research Centrefor Application-specific Integrated Circuit System incollaboration with the Southeast University in Nanjing(Nanjing, China) [3,4].

Formation of the Working Group to apply forthe establishment of the Hong Kong Branch ofCNERCs for Biomaterials

Medical and socioeconomic demands

With significant improvements in living standards in Chinaand the aging population that accompanies these im-provements, the number of patients with significantmusculoskeletal disorders such as osteoporosis and osteo-arthritis has been increasing rapidly. The resulting clinicalor market demand for high-quality orthopaedic bio-materials for clinical applications is very substantial. Ac-cording to official statistics, 100 million patients haveosteoarthritis; as many as 300e400 million patients havetooth defects and tooth loss; 70 million patients haveosteoporosis; nearly 10 million patients each year havebone defects caused by illness, accidents, and sports in-juries; and tens of millions of people require craniofacialand breast cosmetic plastic surgeries [5,6]. The treatmentof these diseases requires biomaterials, thus creating ahuge market for the biomaterial industry. According to thestatistics, the market value of the biotechnology industry,which includes biomaterials, had already exceeded 800billion yuan in 2008 [7].

Biomaterials also have a very promising prospect in otherclinical applications such as in the diagnosis and treatmentof cardiovascular diseases, cancer, and other major dis-eases. Biomaterials are primarily used as medical devices inclinical applications in China and their products account forapproximately 40e50% of the medical devices market [7].Research and development, testing, and clinical translationof biomaterials as a high-value-added, technology-inten-sive, low energy consumption, pollution-free high-tech in-dustry are very consistent with the direction of the futureeconomy in mainland China and in Hong Kong. The

172 L. Bian et al.

establishment of the biomaterials industry will effectivelypromote the health of residents in mainland China and inHong Kong, and greatly promote local economic develop-ment and the creation of high-tech jobs [2e4,8].

As early as the early 1980s, Professor Xingdong Zhang ofthe Sichuan University (Sichuan, China), who is alsoacademician of the Chinese Academy of Engineering (Bei-jing, China) and fellow of the United States NationalAcademy of Engineering (Washington, DC, USA), took thelead in China to develop nearly 20 series and 200 types ofbiomaterial implants for bone, teeth, soft tissue repair, andartificial hip joints. Professor Zhang and his group promotedthe application of these biomaterial products in more than600 hospitals. They also received good outcomes and sixregistration certificates from the State Food and DrugAdministration. In 2000, the National Engineering ResearchCentre for Biomaterials was officially established andbecame the first open national biomaterials professionalR&D institute with a focus on the development of func-tional biomaterial products and clinical translation [1,9].

Figure 1 Paradigm for the clinically driven development ofbiomaterials. CFDA Z China Food and Drug Administration.

Formation of the Application Working Group

As early as 1996, Professor Zhang’s group began collabo-rating with the Department of Orthopaedics and Trauma-tology of the Chinese University of Hong Kong (CUHK;Shatin, Hong Kong) and the Department of Mechanical En-gineering of the Hong Kong University of Sciences andTechnology (HKUST; Clear Water Bay, Hong Kong) ondeveloping translation research on hydroxyapatiteetrical-cium phosphate-based scaffold implantable biomaterialsfor orthopaedic applications [10e12]. In May 2014, underthe backdrop of this development, biomaterial researchersat the CUHKdwho were led by Professor Ling Qin of theFaculty of Medicine, Professor Arthur Mak of the Faculty ofEngineering, and Professor Chi Wu of the Faculty of Scien-cesdproposed to establish a multidisciplinary Hong KongBranch of the National Engineering Research Centre forBiomaterials (hereafter referred to as the Hong KongBranch for Biomaterials). As mentioned previously, theNational Engineering Research Centre for Biomaterials(i.e., the Main Centre listed in the CNERCs) is the onlyNational Engineering Research Centre that focuses on theR&D and translation of biomaterials for clinical applica-tions. Professor Xingdong Zhang (the academic leader ofthe Centre) and Professor Zhongwei Gu (the Director of theCentre and the principal scientist of Program 973) areworld-renowned experts in biomaterials. In China, Profes-sor Zhang has been a pioneer in the research of bioactiveceramics and coatings. His group has developed a series ofbiomedical products for orthopaedic, dental, and otherrelevant medical applications. Their research demon-strated that inanimate calcium phosphate ceramics couldinduce bone formation, and established the prototype ofbiomaterial-induced bone induction theory. ProfessorZhang is also a pioneer in expanding new ways for devel-oping a new generation of biomaterials. Professor Gu hasenjoyed worldwide recognition in the fields of polymer-based biomaterials research, controlled-release systemsfor drugs/bioactive substances, and nanobiomaterials.Since the Centre’s establishment in China, it has had an

indispensable role in the development and translation ofbiomaterials, and has led the technical development andclinical translation of orthopaedic biomaterials [8].

Through an amicable arrangement, the CUHK and theCNERC for Biomaterials have decided to establish the HongKong Branch of the CNERC for Biomaterials at CUHK. Thiseffort in establishing the Hong Kong Branch of Biomaterialsseeks to promote further collaboration with the Main Centrewith the goals of promoting synergy andwin-win cooperationbetween mainland China and Hong Kong in scientificresearch, talent cultivation, clinically driven novel bio-materials product design, and preclinical and clinicaltesting. It will thus become a model for the successfulcollaboration between the Hong Kong research institutionsand themainland CNERCs in the area of biomaterials (Fig. 1).The application for the Hong Kong Branch of CNERC for Bio-materials is built on the foundation of synergistic strengthsand long-term collaboration. These are essential elements intranslational medicine, especially in the R&D of orthopaedicmaterials, implants, and devices [12e19].

Missions of the Hong Kong Branch ofBiomaterials

Through a joint synergistic collaboration with the MainCentre, the Hong Kong Branch of Biomaterials will under-take the following missions to advance the engineering andenterprising of biomaterials in China, especially in HongKong. (1) To innovate biomaterials through their basic sci-ence and their engineering technology, as driven by clinicaldemands. (2) To develop new methods and models toexplore the molecular markers for biocompatibilityresearch and assessment of biomaterials. (3) To conductpreclinical and clinical testing of biomaterials and conductthe associated technology research for clinical applica-tions. (4) To establish jointly with relevant enterprises ademonstrative base for enterprising biomaterials and forthe clinical translation of their products. (5) To nurturejointly with relevant disciplines at the CUHK and SichuanUniversity, advanced professionals with integrative

A model for facilitating translational research and development in China 173

competence in medicine and engineering, and thus offerpostgraduate continuing education for professionals in therelevant industries. (6) To serve as a major window fornational and global collaborations in related sciences andbusinesses for the purpose of academic exchanges, infor-mation mining, and consultative services.

Work of the Hong Kong Branch of Biomaterials

Based on strength (e.g., manpower, infrastructure, trackrecords), the Hong Kong Branch of Biomaterials willcontribute in the following areas. (1) To propose the re-quirements on the design and standards of biomaterials andpromote the clinical applications of mature products, basedon clinical needs. (2) To establish the theoretical andexperimental preclinical models and conduct clinicaltesting and evaluations. (3) To conduct basic research onthe bioactivity and efficacy of biomaterials. (4) To developnovel bioactive and functional biomaterials. (5) To assistthe development and improvement of preparing and pro-cessing technology of advanced biomaterials (which in-cludes three-dimensional printing). (6) To explore theapplications of biomaterials in stem cells, regenerativemedicine, and rehabilitation medicine.

Scope of collaboration with the Main Centre

The Hong Kong Branch of Biomaterials will effectivelycooperate with the Main Centre in mainland China on theR&D of clinical needs-oriented advanced biomaterials,basic research on materials and biology, animal testing, andclinical testing. The specific cooperative measures includeR&D, training, and clinical service (Fig. 1) are as follows. (1)To consolidate and develop in the areas of clinical appli-cations (to further improve and establish indications for theclinical use of biomaterials). (2) To collaborate on programs(i.e. jointly complete the existing programs and jointlyapply for new programs). (3) To share information and in-tellectual property (e.g., data obtained from animal

Figure 2 The management structure and functions of the Hong K

models and clinical testing on biomaterials, new technol-ogy, and new processes for preparation of biomaterials, andinformation of Phase III and Phase IV clinical trials). (4) Toshare resources (e.g., laboratory equipment, facilities, andmedical samples). (5) To exchange talent and training (e.g.,jointly educate postgraduates towards joint postgraduateprogram in biomaterials for medical applications, exchangeand train R&D and management personnel). The Ortho-paedic Learning Centre in CUHK of the applicant unit has a15-year history in training orthopaedic surgeons andresearch scientists in AsianePacific region [20], which willprovide training and education to exchange personnel fromthe Main Centre. (6) To collaborate with existing enter-prises and incubate new businesses, promote effectivecooperation and the development of medical platformswith industrial-academic research partnership. (7) Toconduct clinical studies and evaluations. (8) To providetraining and service for the marketed products.

The potential contributions of the Hong Kong Branch ofBiomaterials to R&D and the translation of biomaterials aresummarized, as follows. (1) To improve and establish in-dications of new biomaterials in clinical uses. (2) To obtaindata on the efficacy of biomaterials in tests with animalmodels and clinical applications and to optimize the prod-ucts. The evaluation of biomaterials in the animal modelsand clinical applications is an essential step during clinicaltranslation. The Hong Kong Branch of Biomaterials hassubstantial scientific experience, experimental equipment,and clinical resources in animal models and clinical testingof biomaterials [21e23]. The Hong Kong Branch of Bio-materials will provide important experimental data forexisting and innovative biomaterials via testing in animalmodels and clinical testing, and thus will have a strong rolein further optimal design and clinical translation of bio-materials. (3) To clarify the molecular mechanism of celland tissue responses to biomaterials. Biomaterials are inclose contact with human tissues and cells. The effects ofbiomaterials on tissues and cells at molecular level deter-mine their normal functions in the human body. The HongKong Branch has a number of world-class scholars and

ong Branch of Biomaterials. R&D Z research and development.

Figure 3 The exchange mechanism between the Main Centre in the list of CNERCs in mainland China and the Hong Kong Branch ofBiomaterials. CNERCs Z Chinese National Engineering Research Centres; Dept. Z department; R&D Z research and development.

1 The Working Group members in the list in the proposal for theHong Kong Branch of CNERC of Biomaterials are the following: TheFaculty of Medicine of the Chinese University of Hong Kong(Shatin, Hong Kong): Professors Ling Qin (Director of the Hong

174 L. Bian et al.

experts in research studies related to molecular biology andcellular biology. The Hong Kong Branch of Biomaterials willmake important contributions in revealing the molecularmechanism of actions of biomaterials on cells and tissues,and thereby effectively promote the optimal design ofbiomaterials and improve the effectiveness of biomaterials[24e26]. (4) To develop novel active and targeted bio-materials. The Hong Kong Branch has strong researchstrengths in materials science, particularly in the fields ofdesign and preclinical and clinical validation of metallicmaterials and polymer materials for medical applications[24e32]. The Hong Kong Branch of Biomaterials will makeimportant contributions to the development of innovativemetallic biomaterials, polymer implant biomaterials, drugcontrolled-release materials and targeted delivery systems,and modification of bioactive molecules on biomaterials.(5) To develop advanced preparation and processing tech-nology for biomaterials. The Hong Kong Branch of Bio-materials has long-term research experience, high-endresearch personnel, and complete research equipment inthe preparation and processing technology for emergingbiomaterials. The Hong Kong Branch will perform effectivework in fields such as three-dimensional printing and sur-face coating technology biomaterials. (6) To study the ap-plications of biomaterials in stem cells, regenerativemedicine, and rehabilitation medicine, the Hong KongBranch of Biomaterials will also focus on the developmentof novel biomaterials, stem cell carriers, transcutaneousimplant materials, advanced exoskeleton materials, andother key technologies that have an important role inpromoting the clinical applications of stem cells and novelrehabilitation biomaterials.

Kong Branch), Chun-Yiu Cheng, Kai Ming Chan, Gang Li, Kwok-SuiLeung, Shekhar-Madhukar Kumta, and Wing-Hoi Cheung. Facultyof Engineering of the Chinese University of Hong Kong (Shatin,Hong Kong): Professors Arthur Mak (codirector of the Hong KongBranch), Charlie Wang, Jonathan Choi, Li Zhang, Wei Hsin Liao,Liming Bian, and Douglas Yung. Faculty of Science of the ChineseUniversity of Hong Kong: Professors Chi Wu [codirector of theHong Kong Branch and academician of the Chinese Academy ofScience (Beijing, China)], Michael Chan, and To Ngai.

Management system and operation mechanismproposed for the Hong Kong Branch ofBiomaterials

Based on synergistic collaboration between medicalexpertise and engineering expertise, the administration

unit of the Hong Kong Branch of Biomaterials will beestablished at the Faculty of Medicine of the CUHK (Shatin,Hong Kong). Professor Ling Qin, who is director of theMusculoskeletal Research Laboratory in the Department ofOrthopaedics and Traumatology of the CUHK, will assumethe post as the director of the Hong Kong Branch. ProfessorFuk-Tat Mak (director of the Biomedical Engineering Divi-sion of the CUHK) and Professor Chi Wu (who is a Wei LunProfessor of Chemistry at the Department of Chemistry ofthe CUHK) will serve as the codirectors of the Hong KongBranch of Biomaterials. To achieve effective managementand implementation of the overall project and tasks, theHong Kong Branch will organize and coordinate the facultymembers who are engaged in teaching and researchingbiomaterials from the Faculty of Medicine, the Faculty ofEngineering, and the Faculty of Science at the CUHK toconsolidate the existing interdisciplinary cooperation andfurther promote collaborative research with the MainCentre. Professor Qin, Professor Mak, and Professor Wu andthe Working Group1 have proposed establishing a multi-centre biomaterial research institute by integratingresearch strengths from the Faculty of Medicine, the Fac-ulty of Engineering, and the Faculty of Science at the CUHK[24e26]. Professor Francis Chan, who is dean of the Facultyof Medicine at the CUHK, will be chairman of the

Figure 4 The diagram shows the complementation and cooperation between the Main Centre and the Hong Kong Branch ofBiomaterials. R&D Z research and development.

A model for facilitating translational research and development in China 175

Management Committee of Hong Kong Branch. Assumingthe post as vice-chairmen are Professor Wong Ching Ping,who is Dean of the Faculty of Engineering and academicianof the Chinese Academy of Engineering (Beijing, China) andthe United States National Academy of Engineering, andProfessor Henry Nai-Ching Wong, who is Dean of the Facultyof Science and academician of Chinese Academy of Sci-ences (Beijing, China). An advisory committee and an ex-ecutive core group, which includes the responsible personsof the Main Centre, will be established. The managementstructures and the functions of the Main Centre of CNERC inmainland China and the Hong Kong Branch have been pro-posed (Fig. 2). The exchange mechanism between the MainCentre and its Hong Kong Branch is also listed for the syn-ergistic running of bilateral collaboration (Fig. 3).

Synergy should be built on a strong foundation ofbiomaterial research at the Main Centre and the Hong KongBranch by the appropriate alignment of research directions(Fig. 4). The establishment of the Hong Kong Branch ofBiomaterials will lead to the development of biomaterialindustries in the region, which is consistent with the na-tional strategic investment in new materials and biomedicaltechnology.

In summary, biomaterials and key technologies havemade great progress in recent years in China. However, alarge gap remains between the technical level of bioma-terial products in China and internationally. Therefore,further development of the biomaterial industry in China isin urgent need of promoting cooperation between different

scientific institutes with complementary strengths. TheNational Engineering Research Centre for Biomaterials andthe Hong Kong Branch of Biomaterials in CUHK jointlyestablished by the Faculty of Medicine, Faculty of Engi-neering, and Faculty of Science of the CUHK will favourablycomplement each other. The establishment of the HongKong Branch of Biomaterials will further enhance the R&Dlevel of biomaterials in China and promote translation andclinical 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 thisarticle.

References

[1] Ministry of Science and Technology of the People’s Republic ofChina [Internet; in Chinese]. www.most.gov.cn. [accessed19.07.14].

[2] Ministry of Science and Technology of the People’s Republic ofChina [Internet; in Chinese]. National Engineering ResearchCenter and National Key Laboratory of reporting subcenters inHong Kong partner laboratory assessment briefing held in Hong

176 L. Bian et al.

Kong. http://www.most.gov.cn/kjbgz/201403/t20140312_112277.htm. [accessed 19.07.14].

[3] University of Hong Kong [Internet]. Vice-Premier of the StateCouncil Li Keqiang attends The University of Hong Kong Cen-tenary Ceremony. http://www.hku.hk/press/news_detail_6552.html. [accessed 19.07.14].

[4] http://www.astri.org/main/?contentnamespaceZnews_room:press_releases:content:20120705ar.

[5] Choong P, Brooks P. Achievements during the bone and jointdecade 2000e2010. Best Pract Res Clin Rheumatol 2012;26:173e81.

[6] Woolf AD, Pfleger B. Burden of major musculoskeletal condi-tions. Bull World Health Organ 2003;81:646e56.

[7] Overview of the Chinese biomaterial industry andmarket; 2012.http://wenku.baidu.com/view/5a513f1d10a6f524ccbf85c5.

[8] Festel G, Kreimeyer A, Oels U, Zedtwitz MV, editors. Thechemical and pharmaceutical industry in China: opportunitiesand threats for foreign companies. Heidelberg, Germany:Springer; 2005.

[9] http://www.biomater.com; http://www.csbm.org.cn/en/index.php?aZart&idZ5.

[10] Guo LH, Guo X, Qin L, Cheng J, Zhang XD. XRPD quantitativeanalysis of biomaterials based on calcium phosphate. In:Proceedings of the 20th Annual International Conference ofthe IEEE-EBMS 1998. Piscataway, NJ: IEEE Engineering inMedicine and Biology Society; 1998. p. 2893e6.

[11] Lu X, Leng Y, Zhang X, Xu J, Qin L, Chan CW. Comparativestudy of osteoconduction on micromachined and alkali-treated titanium alloy surfaces in vitro and in vivo. Bio-materials 2005;26:1793e801.

[12] Butler D. Translational research: crossing the valley of death.Nature 2008;453:840e2.

[13] Jacobs JJ. Translational research: whither the ORS? J OrthopRes 2008;26:737e40.

[14] Zerhouni EA. Translational and clinical science-time for a newvision. N Engl J Med 2005;353:1621e3.

[15] Dai KR, editor. Translational medicine in China: from idea toconcept to implementation. Xian, China: Publishing House ofthe 4th Military University; 2012.

[16] Qin L, Tang TT, Xie XH, Hung LK. Orthopaedic translationalresearch. Chin J Orthop 2009;29:87e9.

[17] Qin L. Translational medicine in orthopaedics. J Orthop Transl2013;1:3e5.

[18] Dai K-R, Yang F, Gan Y-K. Development of translational med-icine in China: foam or feast? J Orthop Transl 2013;1:6e10.

[19] Yuan Y, Lin D, Chen F, Liu C. Clinical translation of biomedicalmaterials and the key factors towards product registration. JOrthop Transl 2014;2:49e55.

[20] Chinese University of Hong Kong [Internet]. Department ofOrthopaedics 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. Advancedbioimaging technologies in assessment of quality of bone andscaffold biomaterials. Heidelberg, Germany: Springer; 2007.

[22] Leung KS, Qin YX, Cheung WH, Qin L, editors. A practicalmanual for musculoskeletal research. Singapore: World Sci-entific 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 thatmimic developmentally relevant matrix and N-cadherin in-teractions enhance MSC chondrogenesis. Proc Natl Acad Sci US A 2013;110:10117e22.

[25] Yue Y, Jin F, Deng R, Cai J, Dai Z, Lin MC, et al. Revisitcomplexation between DNA and polyethylenimine-effect oflength of free polycationic chains on gene transfection. JControl Release 2011;152:143e51.

[26] Zhang G, Guo B, Wu H, Tang T, Zhang BT, Zheng L, et al. Adelivery system targeting bone formation surfaces to facili-tate RNAi-based anabolic therapy. Nat Med 2012;18:307e14.

[27] Xu L, Li G. Circulating mesenchymal stem cells and theirclinical implications. J Orthop Transl 2014;2:1e7.

[28] Tang J, Wang J, Xie X, Zhang P, Lai Y, Li Y, et al. Surfacecoating reduces degradation rate of magnesium alloy devel-oped for orthopaedic applications. J Orthop Transl 2013;1:41e8.

[29] Gu XN, Xie XH, Li N, Zheng YF, Qin L. In vitro and in vivostudies on a Mg-Sr binary alloy system developed as a new kindof 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 skel-etal 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 high-entropy 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)/tricalciumphosphate scaffolds incorporated or coated with osteogenicgrowth factors for enhancement of bone regeneration. JOrthop Transl 2014;2:91e104.