МАТЕРИАЛЫ И МЕТОДЫ ТКАНЕВОЙ ИНЖЕНЕРИИ КОСТНОЙ ТКАНИ

Тканевая инженерия костной ткани ищет альтернативное решение вопроса скелетных увечий. В основе метода лежит создание тканеинженерного эквивалента костной ткани с помощью мультипотентных клеток, матриц-носителей этих клеток и остеогенных факторов. Процесс создания тканеинженерного аналога костной ткани начинается с производства матрицы для культивирования клеток. В статье выполнен обзор наиболее перспективных материалов и методов, используемых для изготовления клеточных матриц. Современные технологии создания клеточных матриц стремятся имитировать структуру естественного внеклеточного матрикса кости на микро- и наноуровнях. Современные материалы, применяемые для создания клеточных матриц, повторяют группы веществ, составляющих естественный внеклеточный матрикс кости. Имитирование естественного состава и строения необходимо для создания оптимальных условий для жизнедеятельности клеток на конструкции, а также для создания выгодных физико-механических характеристик матрицы.

тканевая инженерия костной ткани, клеточная матрица, электроспиннинг, 3D-печать, синтетические биодеградируемые полимеры, соединения естественного внеклеточного матрикса кости, сигнальные молекулы

1. Военная травматология и ортопедия. / Под ред. проф. В.М. Шаповалова. СПб., 2004.

2. Кирилова И.А., Подорожная В.Т., Легостаева Е.В., Шаркеев Ю.П., Уваркин П.В., Аронов А.М. Костно-пластические биоматериалы и их физико-механические свойства // Хирургия позвоночника. 2010. № 1. С. 81-87. DOI: 10.14531/ss2010.1.81-87.

3. Ларионов П.М., Садовой М.А., Самохин А.Г., Рожнова О.М., Гусев А.Ф., Принц В.Я., Селезнев В.А., Голод С.В., Принц А.В., Корнеев И.А., Комонов А.И., Мамонова Е.В., Малютина Ю.Н., Батаев В.А. Создание тканеинженерного эквивалента костной ткани и перспективы его использования в травматологии и ортопедии // Хирургия позвоночника. 2014. № 3. С. 77-85. DOI: http://dx.doi.org/10.14531/ss2014.3.77-85.

4. Материалы Всероссийской научно-практической конференции с международным участием «Современные принципы и технологии остеосинтеза костей конечностей, таза и позвоночника». СПб., 2015.

5. Официальный сайт Всемирной организации здравоохранения [Электронный ресурс]. URL: http://www.who.int/mediacentre/news/releases/2009/road_safety_report_20090615/ru/.

6. Annabi N, Fathi A, Mithieux SM, Martens P, Weiss AS, Dehghani F. The effect of elastin on chondrocyte adhesion and proliferation on poly (3-caprolactone)/elastin composites. Biomaterials. 2011;32:1517-1525. DOI: 10.1016/j.biomaterials.2010.10.024.

7. Bai Y, Yin G, Huang Z, Liao X, Chen X, Yao Y, Pu X. Localized delivery of growth factors for angiogenesis and bone formation in tissue engineering. Int Immunopharmacol. 2013; 16: 214-223. DOI: 10.1016/j.intimp.2013.04.001.

8. Balaji Raghavendran HR, Puvaneswary S, Talebian S, Murali MR, Naveen SV, Krishnamurithy G, McKean R, Kamarul T. A comparative study on in vitro osteogenic priming potential of electron spun scaffold PLLA/HA/Col, PLLA/ HA, and PLLA/Col for tissue engineering application. PloS One. 2014; 9: e104389. DOI: 10.1371/journal.pone.0104389.

9. Bandyopadyay-Ghosh S. Bone as a collagen-hydroxyapatite composite and its repair. Trends Biomater Artif Organs. 2008; 22: 116-124.

10. Barenghi R, Beke S, Romano I, Gavazzo P, Farkas B, Vassali M, Brandi F, Scaglione M. Elastin-coated biodegradable photopolymer scaffolds for tissue engineering applications. BioMed Res Int. 2014; ID 624645. DOI: 10.1155/2014/624645.

11. Bohner M. Resorbable biomaterials as bone graft substitutes. Materials Today. 2010; 13: 24-30. DOI: 10.1016/S1369-7021(10)70014-6.

12. Bose S, Tarafder S, Banerjee SS, Davies NM, Bandyopadhyay A. Understanding in vivo response and mechanical property variation in MgO, SrO and SiO2 doped β-TCP. Bone. 2011; 48: 1282-1290. DOI: 10.1016/j.bone.2011.03.685.

13. Bosetti M, Boccafoschi F, Leigheb M, Cannas MF. Effect of different growth factors on human osteoblasts activities: a possible application in bone regeneration for tissue engineering. Biomol Eng. 2007; 24: 613-618. DOI: 10.1016/j.bioeng.2007.08.019.

14. Choi JW, Wicker R, Lee SH, Choi KH, Ha CS, Chung I. Fabrication of 3D biocompatible/biodegradable micro-scaffolds using dynamic mask projection microstereolithography. J Mater Process Technol. 2009; 209: 5494-5503.

15. Dahlin RL, Kasper FK, Mikos AG. Polymeric nanofibers in tissue engineering. Tissue Eng Part B Rev. 2011; 17: 349-64. DOI: 10.1089/ten.TEB.2011.0238.

16. Deng C, Zhang P, Vulesevic B, Kuraitis D, Li F, Yang AF, Griffith M, Ruel M, Suuronen EJ. A collagen-chitosan hydrogel for endothelial differentiation and angiogenesis. Tissue Eng Part A. 2010; 16: 3099-3109. DOI: 10.1089/ten.tea.2009.0504.

17. Elomaa L, Teixeira S, Hakala R, Korhonen H, Grijpma DW, Seppala JV. Preparation of poly(ε-caprolactone)-based tissue engineering scaffolds by stereolithography. Acta Biomater. 2011; 7: 3850-3856. DOI: 10.1016/j.actbio.2011.06.039.

18. Faghihi, F, Baghaban Eslaminejad M. The effect of nano-scale topography on osteogenic differentiation of mesenchymal stem cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014; 158: 5-16. DOI: 10.5507/bp.2013.013.

19. Gautam S, Dinda AK, Mishra NC. Fabrication and characterization of PCL/gelatin composite nanofibrous scaffold for tissue engineering applications by electrospinning method. Mater Sci Eng C Mater Biol Appl. 2013; 33: 1228-1235. DOI: 10.1016/j.msec.2012.

20. Grgurevic L, Macek B, Mercep M, Jelic M, Smoljanovic T, Erjavec I, Dumic-Cule I, Prgomet S, Durdevic D, Vnuk D, Lipar M, Stejskal M, Kufner V, Brkljacic J, Maticic D, Vukicevic S. Bone morphogenetic protein (BMP) 1-3 enhances bone repair. Biochem Biophys Res Commun. 2011; 408: 25-31. DOI: 10.1016/j.bbrc.2011.03.109.

21. Guda T1, Appleford M, Oh S, Ong JL. A cellular perspective to bioceramic scaffolds for bone tissue engineering: the state of the art. Curr Top Med Chem. 2008; 8: 290-299. DOI: 10.2174/156802608783790956.

22. Gumusderelioglu M, Tuncay EO, Kaynak G, Demirtas TT, Aydin ST, Hakki SS. Encapsulated boron as an osteoinductive agent for bone scaffolds. J Trace Elem Med Biol. 2015; 31: 120-8. DOI: 10.1016/j.jtemb.2015.03.008.

23. Haberstroh K, Ritter K, Kuschnierz J, Bormann KH, Kaps C, Carvalho C, Mulhaupt R, Sittinger M, Gellrich NC. Bone repair by cell-seeded 3D-bioplotted composite scaffolds made of collagen treated tricalciumphosphate or tricalciumphosphate-chitosan-collagen hydrogel or PLGA in ovine critical-sized calvarial defects. J Biomed Mater Res B Appl Biomater. 2010; 93: 520-530. DOI: 10.1002/jbm.b.31611.

24. Haider A, Gupta KC, Kang IK. PLGA/nHA hybrid nanofiber scaffold as a nanocargo carrier of insulin for accelerating bone tissue regeneration. Nanoscale Res Lett. 2014; 9: 314. DOI: 10.1186/1556-276X-9-314.

25. Kaigler D, Avila G, Wisner-Lynch L, Nevins ML, Nevins M, Rasperini G, Lynch SE, Giannobile WV. Platelet-derived growth factor applications in periodontal and peri-implant bone regeneration. Expert Opin Biol Ther. 2011; 11: 375-385. DOI: 10.1517/14712598.2011.554814.

26. Khandalavala K, Jiang J, Shuler FD, Xie J. Electrospun nanofiber scaffolds with gradations in fiber organization. J Vis Exp. 2015; (98): e52626. DOI: 10.3791/52626.

27. Kim J, McBride S, Tellis B, Alvarez-Urena P, Song YH, Dean DD, Sylvia VL, Elgendy H, Ong J, Hollinger JO. Rapid-prototyped PLGA/β-TCP/hydroxyapatite nanocomposite scaffolds in a rabbit femoral defect model. Biofabrication. 2012; 4: 025003. DOI: 10.1088/1758-5082/4/2/025003.

28. Kim SJ, Jang DH, Park WH, Min B. Fabrication and characterization of 3-dimensional PLGA nanofiber/microfiber composite scaffolds. Polymer. 2010; 51: 1320-1327. DOI: 10.1016/j.polymer.2010.01.025.

29. Kim SS, Utsunomiya H, Koski JA, Wu BM, Cima MJ, Sohn J, Mukai K, Griffith LG, Vacanti JP. Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels. Ann Surg. 1998; 228: 8-13. DOI: 10.1097/00000658-199807000-00002.

30. Knudson D. Fundamentals of Biomechanics. Springer, Boston, Mass, USA, 2007. DOI: 10.1007/978-0-387-49312-1.

31. Lam CX, Mo XM, Teoh SH, Hutmacher DW. Scaffold development using 3D printing with a starch-based polymer. Mater Sci Eng C Mater Biol Appl. 2002; 20: 49-56. DOI: 10.1016/S0928-4931(02)00012-7.

32. Lee H, Kim Y, Kim S, Kim G. Mineralized biomimetic collagen/alginate/silica composite scaffolds fabricated by a low-temperature bio-plotting process for hard tissue regeneration: fabrication, characterisation and in vitro cellular activities. J Mater Chem B. 2014; 2: 5785-5798. DOI: 10.1039/C4TB00931B.

33. Lee JS, Hong JM, Jung JW, Shim JH, Oh J-H, Cho DW. 3D printing of composite tissue with complex shape applied to ear regeneration. Biofabrication. 2014; 6: 024103. DOI: 10.1088/1758-5082/6/2/024103.

34. Lee JW, Kang KS, Lee SH, Kim JY, Lee BK, Cho DW. Bone regeneration using a microstereolithography-produced customized poly(propylene fumarate)/diethyl fumarate photopolymer 3D scaffold incorporating BMP-2 loaded PLGA microspheres. Biomaterials. 2011; 32: 744-752. DOI: 10.1016/j.biomaterials.2010.09.035.

35. Lee JY, Choo JE, Choi YS, Suh JS, Lee SJ, Chung CP, Park YJ. Osteoblastic differentiation of human bone marrow stromal cells in self-assembled BMP-2 receptor-binding peptide-amphiphiles. Biomaterials. 2009; 30: 3532-3541. DOI: 10.1016/j.biomaterials.2009.03.018.

36. Lee KW, Wang S, Fox BC, Ritman EL, Yaszemski MJ, Lu L. Poly (propylene fumarate) bone tissue engineering scaffold fabrication using stereolithography: effects of resin formulations and laser parameters. Biomacromolecules. 2007; 8: 1077-1084. DOI: 10.1021/bm060834v.

37. Li C, Vepari C, Jin HJ, Kim HJ, Kaplan DL. Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials. 2006;27:3115-3124. DOI: 10.1016/j.biomaterials.2006.01.022.

38. Li JJ, Kawazoe N, Chen G. Gold nanoparticles with different charge and moiety induce differential cell response on mesenchymal stem cell osteogenesis. Biomaterials. 2015; 54: 226-236. DOI: 10.1016/j.biomaterials.2015.03.001.

39. Lim TC, Chian KS, Leong KF. Cryogenic prototyping of chitosan scaffolds with controlled micro and macro architecture and their effect on in vivo neo-vascularization and cellular infiltration. J Biomed Mater Res A. 2010; 94: 1303-1311. DOI: 10.1002/jbm.a.32747.

40. Lima MJ, Pirraco RP, Sousa RA, Neves NM, Marques AP, Bhattacharya M, Correlo VM, Reis RL. Bottom-up approach to construct microfabricated multi-layer scaffolds for bone tissue engineering. Biomed Microdevices. 2014; 16: 69-78. DOI: 10.1007/s10544-013-9806-4.

41. Luo Z, Deng Y, Zhang R, Wang M, Bai Y, Zhao Q, Lyu Y, Wei J, Wei S. Peptide-laden mesoporous silica nanoparticles with promoted bioactivity and osteodifferentiation ability for bone tissue engineering. Colloids Surf B Biointerfaces. 2015; 131: 73-82. DOI: 10.1016/j.colsurfb.2015.04.043.

42. Maher PS, Keatch RP, Donnelly K, Paxton JZ. Formed 3D bio-scaffolds via rapid prototyping technology. IFMBE Proceedings: 4th European Conference of the International Federation for Medical and Biological Engineering, ed. by J. Vander Sloten; P. Verdonck; M. Nyssen; J. Haueisen. Vol. 22. New York: Springer, 2009: 2200-2204.

43. Maurus PB, Kaeding CC. Bioabsorbable implant material review. Oper Tech Sports Med. 2004; 12: 158-160. DOI: 10.1053/j.otsm.2004.07.015.

44. McCarthy TL, Centrella M, Canalis E. Insulin-like growth factor (IGF) and bone. Connect Tissue Res. 1989; 20: 277-282.

45. McCullen SD, Zhu Y, Bernacki SH, Narayan RJ, Pourdeyhimi B, Gorga RE, Loboa EG. Electrospun composite poly(L-lactic acid)/tricalcium phosphate scaffolds induce proliferation and osteogenic differentiation of human adipose-derived stem cells. Biomed Mater. 2009; 4: 035002. DOI: 10.1088/1748-6041/4/3/035002.

46. Melchels FP, Feijen J, Grijpma DW. A poly (D, L-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography. Biomaterials. 2009; 30: 3801-3809. DOI: 10.1016/j.biomaterials.2009.03.055.

47. Meng ZX, Zheng W, Li L, Zheng Y. Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold. Mater Chem Phys. 2011; 125: 606-611. DOI: 10.1016/j.matchemphys.2010.10.010.

48. Middleton JC, Tipton AJ. Synthetic biodegradable polymers as orthopedic devices. Biomaterials. 2000; 21: 2335-2346. DOI: 10.1016/S0142-9612(00)00101-0.

49. Moon S, Hasan SK, Song YS, Xu F, Keles HO, Manzur F, Mikkilineni S, Hong JW, Nagatomi J, Haeggstrom E, Khademhosseini A, Demirci U. Layer by layer three-dimensional tissue epitaxy by cell-laden hydrogel droplets. Tissue Eng Part C Methods. 2009; 16: 157-166. DOI: 10.1089/ten.TEC.2009.0179.

50. Moreau JL, Xu HH. Mesenchymal stem cell proliferation and differentiation on an injectable calcium phosphate-chitosan composite scaffold. 2009; 30: 2675-2682. DOI: 10.1016/j.biomaterials.2009.01.022.

51. Motamedian SR, Hosseinpour S, Ahsaie MG, Khojasteh A. Smart scaffolds in bone tissue engineering: A systematic review of literature. World J Stem Cells. 2015; 7: 657-668. DOI: 10.4252/wjsc.v7.i3.657.

52. Nandakumar A, Barradas A, de Boer J, Moroni L, van Blitterswijk C, Habibovic P. Combining technologies to create bioactive hybrid scaffolds for bone tissue engineering. Biomatter. 2013; 3: e23705. DOI: 10.4161/biom.23705.

53. Pataky K, Braschler T, Negro A, Renaud P, Lutolf MP, Brugger J. Microdrop printing of hydrogel bioinks into 3d tissue-like geometries. Adv Mater. 2012; 24: 391-396. DOI: 10.1002/adma.201102800.

54. Phipps MC, Clem WC, Grunda JM, Clines GA, Bellis SL. Increasing the pore sizes of bone-mimetic electrospun scaffolds comprised of polycaprolactone, collagen I and hydroxyapatite to enhance cell infiltration. Biomaterials. 2012; 33: 524-534. DOI: 10.1016/j.biomaterials.2011.09.080.

55. Pilehrood MK, Dilamian M, Mirian M, Sadeghi-Aliabadi H, Maleknia L, Nousiainen P, Harlin A. Nanofibrous chitosan-polyethylene oxide engineered scaffolds: a comparative study between simulated structural characteristics and cells viability. Biomed Res Int. 2014; ID 438065. DOI: 10.1155/2014/438065.

56. Samavedi S, Whittington AR, Goldstein AS. Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater. 2013; 9: 8037-8045. DOI: 10.1016/j.actbio.2013.06.014.

57. Schofer MD, Roessler PP, Schaefer J, Theisen C, Schlimme S, Heverhagen JT, Voelker M, Dersch R, Agarwal S, Fuchs-Winkelmann S, Paletta JR. Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects. PLoS ONE. 2011; 6: e25462. DOI: 10.1371/journal.pone.0025462.

58. Seitz H, Rieder W, Irsen S, Leukers B, Tille C. Three-dimensional printing of porous ceramic scaffolds for bone tissue engineering. J Biomed Mater Res B Appl Biomater. 2005; 74: 782-788. DOI: 10.1002/jbm.b.30291.

59. Serra T, Ortiz-Hernandez M, Engel E, Planell JA, Navarro M. Relevance of PEG in PLA-based blends for tissue engineering 3D-printed scaffolds. Mater Sci Eng C Mater Biol Appl. 2014; 38: 55-62. DOI: 10.1016/j.msec.2014.01.003.

60. Shanjani Y, De Croos JN, Pilliar RM, Kandel RA, Toyserkani E. Solid freeform fabrication and characterization of porous calcium polyphosphate structures for tissue engineering purposes. J Biomed Mater Res B Appl Biomater. 2010; 93: 510-519. DOI: 10.1002/jbm.b.31610.

61. Shim JH, Moon TS, Yun MJ, Jeon YC, Jeong CM, Cho DW, Huh JB. Stimulation of healing within a rabbit calvarial defect by a PCL/PLGA scaffold blended with TCP using solid freeform fabrication technology. J Mater Sci Mater Med. 2012; 23: 2993-3002. DOI: 10.1007/s10856-012-4761-9.

62. Van Bael S, Desmet T, Chai YC, Pyka G, Dubruel P, Kruth JP, Schrooten J. In vitro cell-biological performance and structural characterization of selective laser sintered and plasma surface functionalized polycaprolactone scaffolds for bone regeneration. Mater Sci Eng C Mater Biol Appl. 2013;33:3404-3412. DOI: 10.1016/j.msec.2013.04.024.

63. Venkatesan J, Bhatnagar I, Manivasagan P, Kang KH, Kim SK. Alginate composites for bone tissue engineering: a review. Int J Biol Macromol. 2015;72:269-281. DOI: 10.1016/j.ijbiomac.2014.07.008.

64. Won JE, Yun YR, Jang JH, Yang SH, Kim JH, Chrzanowski W, Wall IB, Knowles JC, Kim HW. Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering. Biomaterials. 2015;56:46-57. DOI: 10.1016/j.biomaterials.2015.03.022.

65. Wu BM, Borland SW, Giordano RA, Cima LG, Sachs EM, Cima MJ. Solid free-form fabrication of drug delivery devices. J Control Release. 1996;40:77-87. DOI: 10.1016/0168-3659(95)00173-5.

66. Wu S, Liu X, Yeung KW, Liu C, Yang X. Biomimetic porous scaffolds for bone tissue engineering. Mater Sci Eng R Reports. 2014;80:1-36. DOI:10.1016/j.mser.2014.04.001.

67. Yang F, Murugan R, Wang S, Ramakrishna S. Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials. 2005;26:2603-2610.

68. Yen HJ, Tseng CS, Hsu SH, Tsai CL. Evaluation of chondrocyte growth in the highly porous scaffolds made by fused deposition manufacturing (FDM) filled with type II collagen. Biomed Microdevices. 2009;11:615-624. DOI: 10.1007/s10544-008-9271-7.

69. Zein I, Hutmacher DW, Tan KC, Teoh SH. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials. 2002;23:1169-1185.

70. Zeltinger J, Sherwood JK, Graham DA, Mueller R, Griffith LG. Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition. Tissue Eng. 2001;7:557-572. DOI: 10.1089/107632701753213183.

71. Zhang H, Chen Z. Fabrication and characterization of electrospun PLGA/MWNTs/hydroxyapatite biocomposite scaffolds for bone tissue engineering. J Bioactive Comp Polym. 2010;25:241-255. DOI: 10.1177/0883911509359486.

72. Zhou Y, Yao H, Wang J, Wang D, Liu Q, Li Z. Greener synthesis of electrospun collagen/ hydroxyapatite composite fibers with an excellent microstructure for bone tissue engineering. Int J Nanomedicine. 2015;10:3203-3215. DOI: 10.2147/IJN.S79241.