화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Journal of Industrial and Engineering Chemistry, Vol.33, 1-10, January, 2016
DOI10.1016/j.jiec.2015.10.028  Export Citation
Application of chitosan and chitosan derivatives as biomaterials
Changyong Choi, Joung-Pyo Nam, and Jae-Woon Nah†
  • Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do, Republic of Korea
E-mail:
Chitosan is a linear polysaccharide composed of randomly distributed b-(1-4)-linked D-glucosamine and N-acetyl-D-glucosamine. It is one of the major cationic polymers and the second most abundant polysaccharides in nature. It is extensively used to the biomedical and the industrial fields. Specially, chitosan has been studied much in the field of gene therapy during the last decade for its biocompatibility and non-cytotoxicity. However, it has several problems such as solubility, low transfection efficiency, and low specialty on targeted disease. To solve these problems, various strategies have been reported to enhance them. This review briefly introduces various strategies of chitosan carrier.
Keywords:Chitosan;Chitosan derivatives;Biomaterials;Delivery system
  1. Layek B, Singh J, Biomacromolecules, 14(2), 485 (2013)
  2. Louise C, Methods Mol. Biol., 333, 201 (2006)
  3. Rolland A, Adv. Drug Deliv. Rev., 57, 669 (2005)
  4. Jiang HL, Lim HT, Kim YK, Arote R, Shin JY, Kwon JT, Kim JE, Kim JH, Kim D, Chae C, Nah JW, Choi YJ, Cho CS, Cho MH, Eur. J. Pharm. Biopharm., 77, 36 (2011)
  5. Anderson WF, Science, 256, 808 (1992)
  6. Nayak S, Herzog RW, Gene Ther., 17, 295 (2010)
  7. Zhou HS, Liu DP, Liang CC, Med. Res. Rev., 24, 748 (2004)
  8. Smith AE, Annu. Rev. Microbiol., 49, 807 (1995)
  9. Morille M, Passirani C, Vonarbourg A, Clavreul A, Benoit JP, Biomaterials, 29, 3477 (2008)
  10. Li S, Huang L, Gene Ther., 7, 31 (2000)
  11. Liang YR, Liu ZL, Shuai XT, Wang WW, Liu J, Bi W, Wang CM, Jing XN, Liu YY, Tao EX, Biochem. Biophys. Res. Commun., 421(4), 690 (2012)
  12. Gao X, Kuruba R, Damodaran K, Day BW, Liu D, Li S, J. Control. Release, 137, 38 (2009)
  13. Kiang T, Wen J, Lim HW, Leong KW, Biomaterials, 25, 5293 (2004)
  14. Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP, Proc. Natl. Acad. Sci. U.S.A., 92, 7297 (1995)
  15. Suh J, Paik HJ, Hwang BK, Bioorganic Chem., 22, 318 (1994)
  16. Hoppe-Seiler F, Ber. Dtsch. Chem. Ges., 27, 3329 (1994)
  17. Domard A, Cartier N, Int. J. Biol. Macromol., 14, 100 (1992)
  18. Hejazi R, Amiji M, J. Control. Release, 89, 151 (2003)
  19. Dong CL, Chen W, Liu C, Bioresour. Technol., 170, 239 (2014)
  20. Liu W, Sun S, Cao Z, Zhang X, Yao K, Lu WW, Luk KD, Biomaterials, 26, 2705 (2005)
  21. Sandford PA, Am. Chem. Soc. Div. Polym. Chem., 31, 628 (1990)
  22. Mansouri S, Lavigne P, Corsi K, Benderdour M, Beaumont E, Fernandes JC, Eur. J. Pharm. Biopharm., 57, 1 (2004)
  23. Struszczyk H, Wawro D, Niekraszewicz A, in: Brine CJ, Sandford PA, Zikakis JP (Eds.), Advances in Chitin and Chitosan, Elsevier Applied Science, London, 1991, p. 580.
  24. Chandy T, Sharma CP, Biomater. Artif. Cells Artif. Organs, 18, 1 (1990)
  25. MacLaughlin FC, Mumper RJ, Wang J, Tagliaferri JM, Gill I, Hinchcliffe M, Rolland AP, J. Control. Release, 56, 259 (1998)
  26. Cui Z, Mumper RJ, J. Control. Release, 75, 409 (2001)
  27. Zhao X, Yu SB, Wu FL, Mao ZB, Yu CL, J. Control. Release, 112, 223 (2006)
  28. Weecharangsan W, Opanasopit P, Ngawhirunpat T, Apirakaramwong A, Rojanarata T, Ruktanonchai U, Lee RJ, Int. J. Pharm., 348, 161 (2008)
  29. Niu L, Xu YC, Xie HY, Dai Z, Tang HQ, Acta Pharmacol. Sin., 29, 1342 (2008)
  30. Romoren K, Pedersen S, Smistad G, Evensen O, Thu BJ, Int. J. Pharm., 261, 115 (2003)
  31. Lavertu M, Methot S, Tran-Khanh N, Buschmann MD, Biomaterials, 27, 4815 (2006)
  32. Aiba SI, Int. J. Biol. Macromol., 14, 225 (1992)
  33. Ma PL, Lavertu M, Winnik FM, Buschmann MD, Biomacromolecules, 10(6), 1490 (2009)
  34. Koping-Hoggard M, Varum KM, Issa M, Danielsen S, Christensen BE, Stokke BT, Artursson P, Gene Ther., 11, 1441 (2004)
  35. Koping-Hoggard M, Tubulekas I, Guan H, Edwards K, Nilsson M, Varum KM, Artursson P, Gene Ther., 8, 1108 (2001)
  36. Jang MK, Jeong YI, Cho CS, Yang SH, Kang YE, Nah JW, Bull. Korean Chem. Soc., 23, 914 (2002)
  37. Bloomfield VA, Biopolymers, 44, 269 (1997)
  38. Strand SP, Lelu S, Reitan NK, de Lange Davies C, Artursson P, Varum KM, Biomaterials, 31, 975 (2010)
  39. Akbuga J, Ozbas-Turan S, Erdogan N, Eur. J. Pharm. Biopharm., 58, 501 (2004)
  40. Koping-Hoggard M, Mel’nikova YS, Varum KM, Lindman B, Artursson P, J. Gene. Med., 5, 130 (2003)
  41. Nydert P, Dragomir A, Hjelte L, Biotechnol. Appl. Biochem., 51, 153 (2008)
  42. Guliyeva U, Oner F, Ozsoy S, Haziroglu R, Eur. J. Pharm. Biopharm., 62, 17 (2006)
  43. Nimesh S, Thibault MM, Lavertu M, Buschmann MD, Mol. Biotechnol., 46, 182 (2010)
  44. Centelles MN, Qian C, Campanero MA, Irache JM, Int. J. Nanomed., 3, 451 (2008)
  45. Yuan Y, Tan J, Wang Y, Qian C, Zhang M, Acta Biochim. Biophys. Sin., 41, 515 (2009)
  46. Li XW, Lee DKL, Chan ASC, Alpar HO, BBA - Gene Struct. Expr., 1630, 7 (2003)
  47. Chellat F, Grandjean-Laquerriere A, Naour RL, Fernandes J, Yahia L, Guenounou M, Laurent-Maquin D, Biomaterials, 26, 961 (2005)
  48. Yang PT, Hoang L, Jia WW, Skarsgard ED, J. Surg. Res., 171, 691 (2011)
  49. Yang X, Yuan X, Cai D, Wang S, Zong L, Int. J. Pharm., 375, 123 (2009)
  50. Roy K, Mao HQ, Huang SK, Leong KW, Nat. Med., 5, 387 (1999)
  51. Kumar M, Behera AK, Lockey RF, Zhang J, Bhullar G, De La Cruz CP, Chen LC, Leong KW, Huang SK, Mohapatra SS, Hum. Gene Ther., 13, 1415 (2002)
  52. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T, Nature, 411, 494 (2001)
  53. Ji AM, Su D, Che O, Li WS, Sun L, Zhang ZY, Yang B, Xu F, Nanotechnology, 20, 405103 (2009)
  54. Liao ZX, Ho YC, Chen HL, Peng SF, Hsiao CW, Sung HW, Biomaterials, 31, 8780 (2010)
  55. Song E, Lee SK, Dykxhoorn DM, Novina C, Zhang D, Crawford K, Cemy J, Sharp PA, Lieberman J, Manjunath N, Shankar P, J. Virol., 77, 7174 (2003)
  56. Behlke MA, Mol. Ther., 13, 644 (2006)
  57. Sioud M, Expert Opin. Drug Deliv., 2, 639 (2005)
  58. Howard KA, Rahbek UL, Liu X, Damgaard CK, Glud SZ, Andersen MO, Hovgaard MB, Schmitz A, Nyengaard JR, Besenbacher F, Kjems J, Mol. Ther., 14, 476 (2006)
  59. Liu X, Howard KA, Dong M, Andersen MO, Rahbek UL, Johnsen MG, Hansen OC, Besenbacher F, Kjems J, Biomaterials, 28, 1280 (2007)
  60. Malmo J, Sorgard H, Varum KM, Strand SP, J. Control. Release, 158, 261 (2012)
  61. Nielsen EJ, Nielsen JM, Becker D, Karlas A, Prakash H, Glud SZ, Merrison J, Besenbacher F, Meyer TF, Kjems J, Howard KA, Pharm. Res., 27, 2520 (2010)
  62. Alameh M, Jean M, Dejesus D, Buschmann MD, Merzouki A, Int. J. Nanomed., 5, 473 (2010)
  63. Xu W, Shen Y, Jiang Z, Wang Y, Chu Y, Xiong S, Vaccine, 22, 3603 (2004)
  64. Du YZ, Lu P, Zhou JP, Yuan H, Hu FQ, Int. J. Pharm., 391, 260 (2010)
  65. Hu FQ, Zhao MD, Yuan H, You J, Du YZ, Zeng S, Int. J. Pharm., 315, 158 (2006)
  66. Yoo HS, Lee JE, Chung H, Kwon IC, Jeong SY, J. Control. Release, 103, 235 (2005)
  67. Wang W, Yao J, Zhou JP, Lu Y, Wang Y, Tao L, Li YP, Biochem. Biophys. Res. Commun., 377(2), 567 (2008)
  68. Wang B, He C, Tang C, Yin C, Biomaterials, 32, 4630 (2011)
  69. Mao S, Sun W, Kissel T, Adv. Drug Deliv. Rev., 62, 12 (2010)
  70. Zhang Y, Chen J, Zhang Y, Pan Y, Zhao J, Ren L, Liao M, Hu Z, Kong L, Wang J, Biotechnol. Appl. Biochem., 46, 197 (2007)
  71. Kreppel F, Kochanek S, Mol. Ther., 16, 16 (2008)
  72. Mao Z, Ma L, Jiang Y, Yan M, Gao C, Shen J, Macromol. Biosci., 7, 855 (2007)
  73. Kotze A, Lueben H, de Leeuw B, de Boer B, Verhoef JC, Junginger H, Pharm. Res., 14, 1197 (1997)
  74. van der Merwe SM, Verhoef JC, Verheijden JHM, Kotze AF, Junginger HE, Eur. J. Pharm. Biopharm., 58, 225 (2004)
  75. Kean T, Roth S, Thanou M, J. Control. Release, 103, 643 (2005)
  76. Mao S, Shuai X, Unger F, Wittmar M, Xie X, Kissel T, Biomaterials, 26, 6343 (2005)
  77. Germershaus O, Mao S, Sitterberg J, Bakowsky U, Kissel T, J. Control. Release, 125, 145 (2008)
  78. Verheul RJ, Amidi M, van der Wal S, van Riet E, Jiskoot W, Hennink WE, Biomaterials, 29, 3642 (2008)
  79. Layek B, Singh J, Int. J. Pharm., 447, 182 (2013)
  80. Liu Z, Zhang Z, Zhou C, Jiao Y, Prog. Polym. Sci, 35, 1144 (2010)
  81. Piest M, Engbersen JF, J. Control. Release, 148, 83 (2010)
  82. Kuhn PS, Levin Y, Barbosa MC, Physica A, 274, 8 (1999)
  83. Liu WG, Zhang X, Sun SJ, Sun GJ, Yao KD, Liang DC, Guo G, Zhang JY, Bioconjugate Chem., 14, 782 (2003)
  84. Yan J, Du YZ, Chen FY, You J, Yuan H, Hu FQ, Mol. Pharm. (2013)
  85. Zhu D, Jin X, Leng X, Wang H, Bao J, Liu W, Yao K, Song C, Int. J. Nanomed., 5, 1095 (2010)
  86. Chae SY, Son S, Lee M, Jang MK, Nah JW, J. Control. Release, 109, 330 (2005)
  87. Lee JY, Lee SH, Oh MH, Kim JS, Park TG, Nam YS, J. Control. Release, 162, 407 (2012)
  88. Wong K, Sun G, Zhang X, Dai H, Liu Y, He C, Leong KW, Bioconjugate Chem., 17, 152 (2006)
  89. Lu B, Xu XD, Zhang XZ, Cheng SX, Zhuo RX, Biomacromolecules, 9(10), 2594 (2008)
  90. Zhao QQ, Chen JL, Han M, Liang WQ, Tabata Y, Gao JQ, J. Biosci. Bioeng., 105(1), 65 (2008)
  91. Lu B, Sun YX, Li YQ, Zhang XZ, Zhuo RX, Mol. Biosyst., 5, 629 (2009)
  92. Gao JQ, Zhao QQ, Lv TF, Shuai WP, Zhou J, Tang GP, Liang WQ, Tanata Y, Hu YL, Int. J. Pharm., 387, 286 (2010)
  93. Lu B, Wang CF, Wu DQ, Li C, Zhang XZ, Zhuo RX, J. Control. Release, 137, 54 (2009)
  94. Kim TH, Ihm JE, Choi YJ, Nah JW, Cho CS, J. Control. Release, 93, 389 (2003)
  95. Moreira C, Oliveira H, Pires LR, Simoes S, Barbosa MA, Pego AP, Acta Biomater., 5, 2995 (2009)
  96. Ghosn B, Singh A, Li M, Vlassov AV, Burnett C, Puri N, Roy L, Oligonucleotides, 20, 163 (2010)
  97. de Paula Pansani Oliveira F, Dalla Picola IP, Shi Q, Barbosa HF, Tiera VA, Fernandes JC, Tiera MJ, Nanotechnology, 24, 055101 (2013)
  98. Zhang S, Xu Y, Wang B, Qiao W, Liu D, Li Z, J. Control. Release, 100, 165 (2004)
  99. Pirollo KF, Xu L, Chang EH, Curr. Opin. Mol. Ther., 2, 168 (2000)
  100. Mitry RR, Sarraf CE, Havlik R, Habib NA, Hepatology, 31, 885 (2000)
  101. Xu GW, Sun ZT, Forrester K, Wang XW, Coursen J, Harris CC, Hepatology, 24, 1264 (1996)
  102. Gao S, Chen J, Dong L, Ding Z, Yang YH, Zhang J, Eur. J. Pharm. Biopharm., 60, 327 (2005)
  103. Kim TH, Park IK, Nah JW, Choi YJ, Cho CS, Biomaterials, 25, 3783 (2004)
  104. Lu B, Wu DQ, Zheng H, Quan CY, Zhang XZ, Zhuo RX, Mol. Biosyst., 6, 2529 (2010)
  105. Kim TH, Kim SI, Akaike T, Cho CS, J. Control. Release, 105, 354 (2005)
  106. Gao S, Chen J, Xu X, Ding Z, Yang YH, Hua Z, Zhang J, Int. J. Pharm., 255, 57 (2003)
  107. Song B, Zhang W, Peng R, Huang J, Nie T, Li Y, Jiang Q, Gao R, Colloids Surf. B: Biointerfaces, 70, 181 (2009)
  108. Issa MM, Koping-Hoggard M, Tommeraas K, Varum KM, Christensen BE, Strand SP, Artursson P, J. Control. Release, 115, 103 (2006)
  109. Hashimoto M, Morimoto M, Saimoto H, Shigemasa Y, Yanagie H, Eriguchi M, Sato T, Biotechnol. Lett., 28(11), 815 (2006)
  110. Jiang HL, Kim YK, Arote R, Jere D, Quan JS, Yu JH, Choi YJ, Nah JW, Cho MH, Cho CS, Int. J. Pharm., 375, 133 (2009)
  111. Kim TH, Jin H, Kim HW, Cho MH, Cho CS, Mol. Cancer Ther., 5, 1723 (2006)
  112. Hashimoto M, Morimoto M, Saimoto H, Shigemasa Y, Sato T, Bioconjugate Chem., 17, 309 (2006)
  113. Mansouri S, Cuie Y, Winnik F, Shi Q, Lavigne P, Benderdour M, Beaumont E, Femandes JC, Biomaterials, 27, 2060 (2006)
  114. Chan P, Kurisawa M, Chung JE, Yang YY, Biomaterials, 28, 540 (2007)
  115. Morris VB, Sharma CP, Int. J. Pharm., 389, 176 (2010)
  116. Kadiyala I, Loo Y, Roy K, Rice J, Leong KW, Eur. J. Pharm. Sci., 39, 103 (2010)
  117. Han HD, Mangala LS, Lee JW, Shahzad MM, Kim HS, Shen D, Nam EJ, Mora EM, Stone RL, Lu C, Lee SJ, Roh JW, Nick AM, Lopez-Berestein G, Sood AK, Clin. Cancer Res., 16, 3910 (2010)
  118. Wall DA, Wilson G, Hubbard AL, Cell, 21, 79 (1980)
  119. Ashwell G, Harford J, Annu. Rev. Biochem., 51, 531 (1982)
  120. Fallon RJ, Schwartz AL, J. Biol. Chem., 263, 13159 (1988)
  121. Stahl P, Schlesinger PH, Sigardson E, Rodman JS, Lee YC, Cell, 19, 207 (1980)
  122. Sato T, Sunamoto J, Prog. Lipid Res., 31, 345 (1992)
  123. Lu Y, Low PS, J. Control. Release, 91, 17 (2003)
  124. Kamaly N, Kalber T, Thanou M, Bell JD, Miller AD, Bioconjugate Chem., 20, 648 (2009)
  125. Kim SH, Jeong JH, Cho KC, Kim SW, Park TG, J. Control. Release, 104, 223 (2005)
  126. Liang B, He ML, Xiao ZP, Li Y, Chan CY, Kung HF, Shuai XT, Peng Y, Biochem. Biophys. Res. Commun., 367(4), 874 (2008)
  127. Friden PM, Neurosurgery, 35, 294 (1994)
  128. Quick G, Zyl JV, Haqtrey A, Ariatti M, Drug Deliv., 7, 231 (2000)
  129. Singh M, Curr. Pharm. Des., 5, 443 (1999)
  130. Park JH, Kwon S, Nam JO, Park RW, Chung H, Seo SB, Kim IS, Kwon IC, Jeing SY, J. Control. Release, 95, 579 (2004)
  131. Kim JH, Kim YS, Park K, Kang E, Lee S, Nam HY, Kim K, Park JH, Chi DY, Park RW, Kim IS, Choi K, Kwon IC, Biomaterials, 29, 1920 (2008)
  132. Xie J, Shen Z, Li KC, Danthi N, Int. J. Nanomed., 2, 479 (2007)
  133. Varkouhi AK, Verheul RJ, Schiffelers RM, Lammers T, Storm G, Hennink WE, Bioconjugate Chem., 21, 2339 (2010)
  134. Meng F, Hennink WE, Zhong Z, Biomaterials, 30, 2180 (2009)
  135. Breunig M, Hozsa C, Lungwitz U, Watanabe K, Umeda I, Kato H, Goepferich A, J. Control. Release, 130, 57 (2008)
  136. Loretz B, Thaler M, Bernkop-Schnurch A, Bioconjugate Chem., 18, 1028 (2007)
  137. Langoth N, Kahlbacher H, Schoffmann G, Schmerold I, Schuh M, Franz S, Kurka P, Bernkop-Schnurch A, Pharm. Res., 23, 573 (2006)
  138. Yin L, Ding J, He C, Cui L, Tang C, Yin C, Biomaterials, 30, 5691 (2009)
  139. Lee D, Zhang W, Shirley SA, Kong X, Hellermann GR, Lockey RF, Mohapatra SS, Pharm. Res., 24, 157 (2007)
  140. Martien R, Loretz B, Thaler M, Majzoob S, Bernkop-Schnurch A, J. Biomed. Mater. Res. A, 82, 1 (2007)
  141. Martien R, Loretz B, Sandbichler AM, Schnurch AB, Nanotechnology, 19, 045101 (2008)
  142. Oliveira H, Pires LR, Fernandez R, Martins MC, Simoes S, Pego AP, J. Biomed. Mater. Res. A, 95, 801 (2010)
  143. Kay MA, Glorioso JC, Naldini L, Nat. Med., 7, 33 (2001)
  144. Carrillo-Carrasco N, Chandler RJ, Chandrasekaran S, Venditti CP, Hum. Gene Ther., 21, 1147 (2010)
  145. Malhotra M, Tomaro-Duchesneau C, Prakash S, Biomaterials, 34, 1270 (2013)
  146. Katas H, Dzulkefli NNSN, Sahudin SJ, Nanomaterials, 2012, 1 (2012)
  147. Gao Y, Xu Z, Chen S, Gu W, Chen L, Li Y, Int. J. Pharm., 359, 241 (2008)
  148. Zhao X, Yin L, Ding J, Tang C, Gu S, Yin C, Mao Y, J. Control. Release, 144, 46 (2010)
  149. Csaba N, Koping-Hoggard M, Fernandez-Megia E, Novoa-Carballal R, Riguera R, Alonso MJ, J. Biomed. Nanotechnol., 5, 162 (2009)
  150. Krauland AH, Alonso MJ, Int. J. Pharm., 340, 134 (2007)
  151. de Moura MR, Aouada FA, Avena-Bustillos RJ, McHugh TH, Krochta JM, Mattoso LHC, J. Food Eng., 92(4), 448 (2009)
  152. Gaspar VM, Sousa F, Queiroz JA, Correia IJ, Nanotechnology, 22, 015101 (2011)
  153. Katas H, Alpar HO, J. Control. Release, 115, 216 (2006)
  154. Wang SL, Yao HH, Guo LL, Dong L, Li SG, Gu YP, Cancer Genet. Cytogenet., 190, 8 (2009)
  155. Almond A, Cell. Mol. Life Sci., 64, 1591 (2007)
  156. Menzel EJ, Farr C, Cancer Lett., 131, 3 (1998)
  157. Picart C, Curr. Med. Chem., 15, 685 (2008)
  158. Dierich A, Le Guen E, Messaddeq N, Stoltz JF, Netter P, Schaaf P, Voegel JC, Benkirane-Jessel N, Adv. Mater., 19(5), 693 (2007)
  159. Lerner LE, Schwartz DM, Hwang DG, Howes EL, Stern R, Exp. Eye Res., 67, 481 (1998)
  160. Zhu SN, Nolle B, Duncker G, Br. J. Ophthalmol., 81, 80 (1997)
  161. de la Fuente M, Seijo B, Alonso MJ, Invest. Ophthalmol. Vis. Sci., 49, 2016 (2008)
  162. Ravina M, Cubillo E, Olmeda D, Novoa-Carballal R, Fernandez-Megia E, Riguera R, Sanchez A, Cano A, Alonso MJ, Pharm. Res., 27, 2544 (2010)
  163. Lin QK, Ren KF, Ji J, Colloids Surf. B: Biointerfaces, 74, 298 (2009)
  164. Lu HD, Zhao HQ, Wang K, Lv LL, Int. J. Pharm., 420, 358 (2011)
  165. Peng SF, Yang MJ, Su CJ, Chen HL, Lee PW, Wei MC, Sung HW, Biomaterials, 30, 1797 (2009)
  166. Lin YH, Sonaje K, Lin KM, Juang JH, Mi FL, Yang HW, Sung HW, J. Control. Release, 132, 141 (2008)
  167. Lin YH, Chen CT, Liang HF, Kulkarni AR, Lee PW, Chen CH, Sung HW, Nanotechnology, 18, 105102 (2007)
  168. Wang X, Uto T, Akagi T, Akashi M, Baba M, J. Med. Virol., 80, 11 (2008)
  169. Kurosaki T, Kitahara T, Fumoto S, Nishida K, Nakamura J, Niidome T, Kodama Y, Nakagawa H, To H, Sasaki H, Biomaterials, 30, 2846 (2009)
  170. Peng SF, Tseng MT, Ho YC, Wei MC, Liao ZX, Sung HW, Biomaterials, 32, 239 (2011)