- 1. Department of Orthopedics, the Fourth Central Hospital of Baoding City, Baoding Hebei, 072350, P.R.China;
- 2. Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, P.R.China;
With the in-depth research on bone repair process, and the progress in bone repair materials preparation and characterization, a variety of artificial bone substitutes have been fully developed in the treatment of bone related diseases such as bone defects. However, the current various natural or synthetic biomaterials are still unable to achieve the structure and properties of natural bone. Carbon nanotubes (CNTs) have provided a new direction for the development of new materials in the field of bone repair due to their excellent structural stability, mechanical properties, and functional group modifiability. Moreover, CNTs and their composites have broad prospects in the design of bone repair materials and as drug delivery carriers. This paper describes the advantages of CNTs related to bone tissue regeneration from the aspects of morphology, chemistry, mechanics, electromagnetism, and biosafety, as well as the application of CNTs in drug delivery carriers and reinforcement components of scaffold materials. In addition, the potential problems and prospects of CNTs in bone regenerative medicine are discussed.
Citation: REN Yixing, HUANG Ruoyu, WANG Cunyang, MA Yajie, LI Xiaoming. Advantages and challenges of carbon nanotubes as bone repair materials. Chinese Journal of Reparative and Reconstructive Surgery, 2021, 35(3): 271-277. doi: 10.7507/1002-1892.202009073 Copy
1. | Pariente E, Olmos JM, Landeras R, et al. Relationship between spinal osteoarthritis and vertebral fractures in men older than 50 years: data from the Camargo Cohort Study. J Bone Miner Metab, 2017, 35(1): 114-121. |
2. | Cimatti B, Santos MAD, Brassesco MS, et al. Safety, osseointegration, and bone ingrowth analysis of PMMA-based porous cement on animal metaphyseal bone defect model. J Biomed Mater Res B Appl Biomater, 2018, 106(2): 649-658. |
3. | Tran SD, Liu YN, Xia DS, et al. Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation. PLoS ONE, 2013, 8(4): e61632. |
4. | Amorosa LF, Lee CH, Aydemir AB, et al. Physiologic load-bearing characteristics of autografts, allografts, and polymer-based scaffolds in a critical sized segmental defect of long bone: an experimental study. Int J Nanomedicine, 2013, 8: 1637-1643. |
5. | Trzeciak T, Rybka J, Richter M, et al. Cells and nanomaterial-based tissue engineering techniques in the treatment of bone and cartilage injuries. Nanosci Nanotechnol, 2016, 16: 8948-8952. |
6. | Roseti L, Parisi V, Petretta M, et al. Scaffolds for bone tissue engineering: state of the art and new perspectives. Mater Sci Eng C Mater Biol Appl, 2017, 78: 1246-1262. |
7. | Roberts TT, Rosenbaum AJ. Bone grafts, bone substitutes and orthobiologics: the bridge between basic science and clinical advancements in fracture healing. Organogenesis, 2012, 8(4): 114-124. |
8. | Mirmusavi MH, Zadehnajar P, Semnani D, et al. Evaluation of physical, mechanical and biological properties of poly 3-hydroxybutyrate-chitosan-multiwalled carbon nanotube/silk nano-micro composite scaffold for cartilage tissue engineering applications. Int J Biol Macromol, 2019, 132: 822-835. |
9. | Dorj B, Won JE, Kim JH, et al. Robocasting nanocomposite scaffolds of poly(caprolactone)/hydroxyapatite incorporating modified carbon nanotubes for hard tissue reconstruction. J Biomed Mater Res A, 2013, 101(6): 1670-1681. |
10. | Holmes B, Fang XQ, Zarate A, et al. Enhanced human bone marrow mesenchymal stem cell chondrogenic differentiation in electrospun constructs with carbon nanomaterials. Carbon, 2016, 97: 1-13. |
11. | Pei BQ, Wang W, Dunne N, et al. Applications of carbon nanotubes in bone tissue regeneration and engineering: superiority, concerns, current advancements, and prospects. Nanomaterials (Basel), 2019, 9(10): 1501. |
12. | Du Z, Feng X, Cao G, et al. The effect of carbon nanotubes on osteogenic functions of adipose-derived mesenchymal stem cells in vitro and bone formation in vivo compared with that of nano-hydroxyapatite and the possible mechanism. Bioact Mater, 2020, 6(2): 333-345. |
13. | Valverde TM, Castro EG, Cardoso MH, et al. A novel 3D bone-mimetic scaffold composed of collagen/MTA/MWCNT modulates cell migration and osteogenesis. Life Sci, 2016, 162: 115-124. |
14. | Li HP, Sun XW, Li YJ, et al. Carbon nanotube-collagen@hydroxyapatite composites with improved mechanical and biological properties fabricated by a multi in situ synthesis process. Biomedical Microdevices, 2020, 22: 64. |
15. | Liu X, George MN, Park S, et al. 3D-printed scaffolds with carbon nanotubes for bone tissue engineering: Fast and homogeneous one-step functionalization. Acta Biomater, 2020, 111: 129-140. |
16. | Li X, Liu H, Niu X, et al. The use of carbon nanotubes to induce osteogenic differentiation of human adipose-derived MSCs in vitro and ectopic bone formation in vivo. Biomaterials, 2012, 33(19): 4818-4827. |
17. | Khalid P, Suman VB. Carbon nanotube-hydroxyapatite composite for bone tissue engineering and their interaction with mouse fibroblast L929 in vitro. Bionanosci, 2017, 11(3): 233-240. |
18. | Wojtek T, Manish C, Federico S. The chemical and physical characteristics of single-walled carbon nanotube film impact on osteoblastic cell response. Nanotechnology, 2010, 21(31): 315102. |
19. | Zhu JH, Wei SY, Ryu J, et al. In situ stabilized carbon nanofiber (CNF) reinforced epoxy nanocomposites. Mater Chem, 2010, 20: 4937-4948. |
20. | Gautam V, Singh KP, Yadav VL. Polyaniline/multiwall carbon nanotubes/starch nanocomposite material and hemoglobin modified carbon paste electrode for hydrogen peroxide and glucose biosensing. Int J Biol Macromol, 2018, 111: 1124-1132. |
21. | Peyvandi A, Soroushian P, Abdol N, et al. Surface-modified graphite nanomaterials for improved reinforcement efficiency in cementitious paste. Carbon, 2013, 63: 175-186. |
22. | Shen WZ, Li ZJ, Liu YH. Surface chemical functional groups modification of porous carbon. Recent Pat Chem Eng, 2008, 1(1): 27-40. |
23. | Venkatesan J, Pallela R, Kim SK. Applications of carbon nanomaterials in bone tissue engineering. J Biomed Nanotechnol, 2014, 10(10): 3105-3123. |
24. | Wang CY, Cao GX, Zhao TX, et al. Terminal group modification of carbon nanotubes determines covalently bound osteogenic peptide performance. ACS Biomater Sci Eng, 2020, 6: 865-878. |
25. | Wu W, Chen W, Lin D, et al. Influence of surface oxidation of multiwalled carbon nanotubes on the adsorption affinity and capacity of polar and nonpolar organic compounds in aqueous phase. Environ Sci Technol, 2012, 46(10): 5446-5454. |
26. | Kang ES, Kim DS, Suhito IR, et al. Guiding osteogenesis of mesenchymal stem cells using carbon-based nanomaterials. Nano Converg, 2017, 4(1): 2. |
27. | Gupta A, Woods MD, Illingworth KD, et al. Single walled carbon nanotube composites for bone tissue engineering. J Orthop Res, 2013, 31(9): 1374-1381. |
28. | Kiran S, Nune KC, Misra RD. The significance of grafting collagen on polycaprolactone composite scaffolds: processing-structure-functional property relationship. J Biomed Mater Res A, 2015, 103(9): 2919-2931. |
29. | Cirillo G, Hampel S, Spizzirri UG, et al. Carbon nanotubes hybrid hydrogels in drug delivery: A perspective review. Biomed Res, 2014, 2014: 825017. |
30. | Usui Y, Aoki K, Narita N, et al. Carbon nanotubes with high bone-tissue compatibility and bone-formation acceleration effects. Small, 2008, 4(2): 240-246. |
31. | La WG, Jin M, Park S, et al. Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for bone regeneration. Int J Nanomedicine, 2014, 9 Suppl 1(Suppl 1): 107-116. |
32. | Murugan E, Arumugam S. New dendrimer functionalized multi-walled carbon nanotube hybrids for bone tissue engineering. RSC Adv, 2014, 4: 35428-35441. |
33. | Li Z, de Barros ALB, Soares DCF, et al. Functionalized single-walled carbon nanotubes: cellular uptake, biodistribution and applications in drug delivery. Int J Pharm, 2017, 524(1-2): 41-54. |
34. | Sahoo NG, Pan YZ, Li L, et al. Nanocomposites for bone tissue regeneration. Nanomedicine (Lond), 2013, 8(4): 639-653. |
35. | Munir KS, Wen C, Li Y. Carbon nanotubes and graphene as nanoreinforcements in metallic biomaterials: A review. Adv Biosyst, 2019, 3: 2366-7478. |
36. | Kim HW. Biomedical nanocomposites of hydroxyapatite/polycaprolactone obtained by surfactant mediation. J Biomed Mater Res A, 2007, 83(1): 169-177. |
37. | Neubauer E, Kitzmantel M, Hulman M, et al. Potential and challenges of metal-matrix-composites reinforced with carbon nanofibers and carbon nanotubes. Compos Sci Technol, 2010, 70(16): 2228-2236. |
38. | 肖镇昆, 吴磊, 米饶, 等. 碳纳米管对羟基磷灰石基复合材料力学性能的影响. 无机化学学报, 2015, 31(1): 114-120. |
39. | Qian D, Dickey EC, Andrew R, et al. Load transfer and deformation mechanisms in carbon nanotube-polystyrene composites. Appl Phys Lett, 2000, 76: 2868-2870. |
40. | Newman P, Minett A, Ellis-Behnke R, et al. Carbon nanotubes: their potential and pitfalls for bone tissue regeneration and engineering. Nanomedicine, 2013, 9(8): 1139-1158. |
41. | Maiti D, Tong XM, Mou XZ, et al. Carbon-based nanomaterials for biomedical applications: A recent study. Front Pharmacol, 2019, 9: 1401. |
42. | Lee WC, Lim CH, Kenry N, et al. Cell-assembled graphene biocomposite for enhanced chondrogenic differentiation. Small, 2015, 11(8): 963-969. |
43. | Ferrer-Anglada N, Gomis V, El-Hachemi Z, et al. Carbon nanotube based composites for electronic applications: CNT-conducting polymers, CNT-Cu. Phys Status Solidi, 2010, 203(6): 1082-1087. |
44. | Saha A, Jiang C, Martí AA. Carbon nanotube networks on different platforms. Carbon, 2014, 79: 1-18. |
45. | Shanta AS, Al Mamun KA, Islam SK, et al. Carbon nanotubes, nanofibers and nanospikes for electrochemical sensing: A review. Int High Speed Electron Syst, 2017, 26(3): 25-36. |
46. | Mercante LA, Pavinatto A, Iwaki LE, et al. Electrospun polyamide 6/poly(allylamine hydrochloride) nanofibers functionalized with carbon nanotubes for electrochemical detection of dopamine. ACS Appl Mater Interfaces, 2015, 7(8): 4784-4790. |
47. | Mackle JN, Blond DJ, Mooney E, et al. In vitro characterization of an electroactive carbon-nanotube-based nanofiber scaffold for tissue engineering. Macromol Biosci, 2011, 11(9): 1272-1282. |
48. | Cunha C, Panseri S, Iannazzo D, et al. Hybrid composites made of multiwalled carbon nanotubes functionalized with Fe3O4 nanoparticles for tissue engineering applications. Nanotechnol, 2012, 23(46): 465102. |
49. | Kaur T, Kulanthaivel S, Arunachalam T, et al. Biological and mechanical evaluation of poly(lactic-co-glycolic acid) based composites reinforced with one, two and three dimensional carbon biomaterials for bone tissue regeneration. Biomed Mater, 2017, 12(2): 025012. |
50. | Díaz E, Puerto I, Sandonis I, et al. Hydrolytic degradation and cytotoxicity of poly(lactic-co-glycolic acid)/multiwalled carbon nanotubes for bone regeneration. Appl Polym Sci, 2020, 137(10): 48439. |
51. | Elgrabli D, Dachraoui W, Ménard-Moyon C, et al. Carbon nanotube degradation in macrophages: live nanoscale monitoring and understanding of biological pathway. ACS Nano, 2015, 9(10): 10113-10124. |
52. | Takanashi S, Hara K, Aoki K, et al. Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice. Sci Rep, 2012, 2: 498. |
53. | Nomura H, Takanashi S, Tanaka M, et al. Specific biological responses of the synovial membrane to carbon nanotubes. Sci Rep, 2015, 5: 14314. |
54. | Sobajima A, Haniu H, Nomura H, et al. Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice. Int J Nanomedicine, 2019, 14: 6465-6480. |
55. | Yang ST, Wang X, Jia G, et al. Long-term accumulation and low toxicity of single-walled carbon nanotubes in intravenously exposed mice. Toxicol Lett, 2008, 181(3): 182-189. |
56. | Yang Z, Zhang Y, Yang Y, et al. Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomedicine, 2010, 6(3): 427-441. |
57. | Murakami T, Ajima K, Miyawaki J, et al. Drug-loaded carbon nanohorns: adsorption and release of dexamethasone in vitro. Mol Pharm, 2004, 1(6): 399-405. |
58. | Bianco A, Kostarelos K, Prato M. Opportunities and challenges of carbon-based nanomaterials for cancer therapy. Expert Opin Drug Deliv, 2008, 5(3): 331-342. |
59. | Sukhodub LB, Sukhodub LF, Prylutskyy YI, et al. Composite material based on hydroxyapatite and multi-walled carbon nanotubes filled by iron: Preparation, properties and drug release ability. Mater Sci Eng C Mater Biol Appl, 2018, 93: 606-614. |
60. | Bhirde AA, Patel S, Sousa AA, et al. Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice. Nanomedicine (Lond), 2010, 5(10): 1535-1546. |
61. | Kam NW, O’Connell M, Wisdom JA, et al. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc Natl Acad Sci U S A, 2005, 102(33): 11600-11605. |
62. | Kamalha E, Shi XY, Mwasiagi JI, et al. Nanotechnology and carbon nanotubes; A review of potential in drug delivery. Macromol Res, 2012, 20: 891-898. |
63. | Vankoningsloo S, Piret JP, Saout C, et al. Cytotoxicity of multi-walled carbon nanotubes in three skin cellular models: effects of sonication, dispersive agents and corneous layer of reconstructed epidermis. Nanotoxicology, 2010, 4(1): 84-97. |
64. | Mukherjee S, Nandi SK, Kundu B, et al. Enhanced bone regeneration with carbon nanotube reinforced hydroxyapatite in animal model. J Mech Behav Biomed Mater, 2016, 60: 243-255. |
65. | Mirjalili F, Mohammadi H, Azimi M, et al. Synthesis and characterization of β-TCP/CNT nanocomposite: Morphology, microstructure and in vitro bioactivity. Ceramics International, 2017, 43(10): 7573-7580. |
66. | Metoki N, Rosa CMR, Zanin H, et al. Electrodeposition and biomineralization of nano-beta-tricalcium phosphate on graphenated carbon nanotubes. Surface & Coatings Technology, 2016, 297: 51-57. |
67. | Shrestha Sita, Shrestha BK, Ko SW, et al. Engineered cellular microenvironments from functionalized multiwalled carbon nanotubes integrating Zein/Chitosan@Polyurethane for bone cell regeneration. Carbohydrate Polymers, 2020, 251: 117035. |
68. | Carson L, Kelly-Brown C, Stewart M, et al. Synthesis and characterization of chitosan-carbon nanotube composites. Mater Lett, 2009, 63(6-7): 617-620. |
69. | Hirata E, Uo M, Takita H, et al. Multiwalled carbon nanotube-coating of 3D collagen scaffolds for bone tissue engineering. Carbon, 2011, 49(10): 3284-3291. |
70. | Meng Z, He JK, Xia ZX, et al. Fabrication of microfibrous PCL/MWCNTs scaffolds via melt-based electrohydrodynamic printing. Materials Letters, 2020, 278(1): 128440. |
71. | Swietek M, Broz A, Tarasiuk J, et al. Carbon nanotube/iron oxide hybrid particles and their PCL-based 3D composites for potential bone regeneration. Materials Science and Engineering: C, 2019, 104: 109913. |
72. | Kołodziej A, Wesełucha-Birczyńska A, Świętek M, et al. A 2D-Raman correlation spectroscopy study of the interaction of the polymer nanocomposites with carbon nanotubes and human osteoblast-like cells interface. Journal of Molecular Structure, 2020, 1212: 128135. |
73. | De Moura NK, Martins EF, Oliveira RLMS, et al. Synergistic effect of adding bioglass and carbon nanotubes on poly (lactic acid) porous membranes for guided bone regeneration. Materials Science and Engineering: C, 2020, 117: 111327. |
74. | Seligra PG, Nuevo F, Lamanna M, et al. Covalent grafting of carbon nanotubes to PLA in order to improve compatibility. Composites Part B: Engineering, 2013, 46: 61-68. |
75. | 原伟. 功能性碳纳米管的制备及其在活体内组织分布和代谢的初步研究. 太原: 山西医科大学, 2008. |
76. | Wang JT, Fabbro C, Venturelli E, et al. The relationship between the diameter of chemically-functionalized multi-walled carbon nanotubes and their organ biodistribution profiles in vivo. Biomaterials, 2014, 35(35): 9517-9528. |
77. | Lacerda L, Ali-Boucetta H, Herrero MA, et al. Tissue histology and physiology following intravenous administration of different types of functionalized multiwalled carbon nanotubes. Nanomedicine (Lond), 2008, 3(2): 149-161. |
78. | Kolosnjaj-Tabi J, Hartman KB, Boudjemaa S, et al. In vivo behavior of large doses of ultrashort and full-length single-walled carbon nanotubes after oral and intraperitoneal administration to Swiss mice. ACS Nano, 2010, 4(3): 1481-1492. |
79. | Lacerda L, Herrero MA, Venner K, et al. Carbon-nanotube shape and individualization critical for renal excretion. Small, 2008, 4(8): 1130-1132. |
80. | Haniu H, Saito N, Matsuda Y, et al. Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells. Int J Nanomedicine, 2014, 9: 1979-1990. |
81. | Sargent LM, Reynolds SH, Castranova V. Potential pulmonary effects of engineered carbon nanotubes: in vitro genotoxic effects. Nanotoxicology, 2010, 4: 396-408. |
82. | Naya M, Kobayashi N, Mizuno K, et al. Evaluation of the genotoxic potential of single-wall carbon nanotubes by using a battery of in vitro and in vivo genotoxicity assays. Regul Toxicol Pharmacol, 2011, 61(2): 192-198. |
83. | Magrez A, Kasas S, Salicio V, et al. Cellular toxicity of carbon-based nanomaterials. Nano Lett, 2006, 6(6): 1121-1125. |
84. | Jacobsen NR, Pojana G, White P, et al. Genotoxicity, cytotoxicity, and reactive oxygen species induced by single-walled carbon nanotubes and C(60) fullerenes in the FE1-Mutatrade markMouse lung epithelial cells. Environ Mol Mutagen, 2008, 49(6): 476-487. |
85. | Di Sotto A, Chiaretti M, Carru GA, et al. Multi-walled carbon nanotubes: Lack of mutagenic activity in the bacterial reverse mutation assay. Toxicol Lett, 2009, 184(3): 192-197. |
86. | Lewinski N, Colvin V, Drezek, R, et al. Cytotoxicity of nanoparticles. Small, 2009, 4(1): 26-49. |
87. | Sharma S, Naskar S, Kuotsu, K. A review on carbon nanotubes: Influencing toxicity and emerging carrier for platinum based cytotoxic drug application. Drug Deliv Sci Technolo, 2019, 51: 708-720. |
88. | Che Abdullah CA, Azad CL, Ovalle-Robles R, et al. Primary liver cells cultured on carbon nanotube substrates for liver tissue engineering and drug discovery applications. ACS Appl Mater Interfaces, 2014, 6(13): 10373-10380. |
89. | Yu HY, Yao JM, Qin ZY, et al. Comparison of covalent and noncovalent interactions of carbon nanotubes on the crystallization behavior and thermal properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate). Appl Polym Sci, 2013, 130(6): 4299-4307. |
90. | Haniu H, Saito N, Matsuda Y, et al. Effect of dispersants of multi-walled carbon nanotubes on cellular uptake and biological responses. Int J Nanomedicine, 2011, 6: 3295-3307. |
91. | Nazeri Niloofar, Derakhashan MA, Fardi-Majidi A, et al. Novel electro-conductive nanocomposites based on electrospun PLGA/CNT for biomedical applications. Journal of Materials Science Materials in Medicine, 2018, 29: 168. |
92. | Niroula J, Premaratne G, Ali Shojaee S, et al. Combined covalent and noncovalent carboxylation of carbon nanotubes for sensitivity enhancement of clinical immunosensors. Chem Commun (Camb), 2016, 52(88): 13039-13042. |
93. | Usrey ML, Strano MS. Controlling single-walled carbon nanotube surface adsorption with covalent and noncovalent functionalization. Phys Chem C, 2009, 113: 12443-12453. |
94. | Rezvova MA, Yuzhalin AE, Glushkova TV, et al. Biocompatible nanocomposites based on poly(styrene-block-isobutylene-block-styrene) and carbon nanotubes for biomedical application. Polymers, 2020, 12(9): 2158. |
- 1. Pariente E, Olmos JM, Landeras R, et al. Relationship between spinal osteoarthritis and vertebral fractures in men older than 50 years: data from the Camargo Cohort Study. J Bone Miner Metab, 2017, 35(1): 114-121.
- 2. Cimatti B, Santos MAD, Brassesco MS, et al. Safety, osseointegration, and bone ingrowth analysis of PMMA-based porous cement on animal metaphyseal bone defect model. J Biomed Mater Res B Appl Biomater, 2018, 106(2): 649-658.
- 3. Tran SD, Liu YN, Xia DS, et al. Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation. PLoS ONE, 2013, 8(4): e61632.
- 4. Amorosa LF, Lee CH, Aydemir AB, et al. Physiologic load-bearing characteristics of autografts, allografts, and polymer-based scaffolds in a critical sized segmental defect of long bone: an experimental study. Int J Nanomedicine, 2013, 8: 1637-1643.
- 5. Trzeciak T, Rybka J, Richter M, et al. Cells and nanomaterial-based tissue engineering techniques in the treatment of bone and cartilage injuries. Nanosci Nanotechnol, 2016, 16: 8948-8952.
- 6. Roseti L, Parisi V, Petretta M, et al. Scaffolds for bone tissue engineering: state of the art and new perspectives. Mater Sci Eng C Mater Biol Appl, 2017, 78: 1246-1262.
- 7. Roberts TT, Rosenbaum AJ. Bone grafts, bone substitutes and orthobiologics: the bridge between basic science and clinical advancements in fracture healing. Organogenesis, 2012, 8(4): 114-124.
- 8. Mirmusavi MH, Zadehnajar P, Semnani D, et al. Evaluation of physical, mechanical and biological properties of poly 3-hydroxybutyrate-chitosan-multiwalled carbon nanotube/silk nano-micro composite scaffold for cartilage tissue engineering applications. Int J Biol Macromol, 2019, 132: 822-835.
- 9. Dorj B, Won JE, Kim JH, et al. Robocasting nanocomposite scaffolds of poly(caprolactone)/hydroxyapatite incorporating modified carbon nanotubes for hard tissue reconstruction. J Biomed Mater Res A, 2013, 101(6): 1670-1681.
- 10. Holmes B, Fang XQ, Zarate A, et al. Enhanced human bone marrow mesenchymal stem cell chondrogenic differentiation in electrospun constructs with carbon nanomaterials. Carbon, 2016, 97: 1-13.
- 11. Pei BQ, Wang W, Dunne N, et al. Applications of carbon nanotubes in bone tissue regeneration and engineering: superiority, concerns, current advancements, and prospects. Nanomaterials (Basel), 2019, 9(10): 1501.
- 12. Du Z, Feng X, Cao G, et al. The effect of carbon nanotubes on osteogenic functions of adipose-derived mesenchymal stem cells in vitro and bone formation in vivo compared with that of nano-hydroxyapatite and the possible mechanism. Bioact Mater, 2020, 6(2): 333-345.
- 13. Valverde TM, Castro EG, Cardoso MH, et al. A novel 3D bone-mimetic scaffold composed of collagen/MTA/MWCNT modulates cell migration and osteogenesis. Life Sci, 2016, 162: 115-124.
- 14. Li HP, Sun XW, Li YJ, et al. Carbon nanotube-collagen@hydroxyapatite composites with improved mechanical and biological properties fabricated by a multi in situ synthesis process. Biomedical Microdevices, 2020, 22: 64.
- 15. Liu X, George MN, Park S, et al. 3D-printed scaffolds with carbon nanotubes for bone tissue engineering: Fast and homogeneous one-step functionalization. Acta Biomater, 2020, 111: 129-140.
- 16. Li X, Liu H, Niu X, et al. The use of carbon nanotubes to induce osteogenic differentiation of human adipose-derived MSCs in vitro and ectopic bone formation in vivo. Biomaterials, 2012, 33(19): 4818-4827.
- 17. Khalid P, Suman VB. Carbon nanotube-hydroxyapatite composite for bone tissue engineering and their interaction with mouse fibroblast L929 in vitro. Bionanosci, 2017, 11(3): 233-240.
- 18. Wojtek T, Manish C, Federico S. The chemical and physical characteristics of single-walled carbon nanotube film impact on osteoblastic cell response. Nanotechnology, 2010, 21(31): 315102.
- 19. Zhu JH, Wei SY, Ryu J, et al. In situ stabilized carbon nanofiber (CNF) reinforced epoxy nanocomposites. Mater Chem, 2010, 20: 4937-4948.
- 20. Gautam V, Singh KP, Yadav VL. Polyaniline/multiwall carbon nanotubes/starch nanocomposite material and hemoglobin modified carbon paste electrode for hydrogen peroxide and glucose biosensing. Int J Biol Macromol, 2018, 111: 1124-1132.
- 21. Peyvandi A, Soroushian P, Abdol N, et al. Surface-modified graphite nanomaterials for improved reinforcement efficiency in cementitious paste. Carbon, 2013, 63: 175-186.
- 22. Shen WZ, Li ZJ, Liu YH. Surface chemical functional groups modification of porous carbon. Recent Pat Chem Eng, 2008, 1(1): 27-40.
- 23. Venkatesan J, Pallela R, Kim SK. Applications of carbon nanomaterials in bone tissue engineering. J Biomed Nanotechnol, 2014, 10(10): 3105-3123.
- 24. Wang CY, Cao GX, Zhao TX, et al. Terminal group modification of carbon nanotubes determines covalently bound osteogenic peptide performance. ACS Biomater Sci Eng, 2020, 6: 865-878.
- 25. Wu W, Chen W, Lin D, et al. Influence of surface oxidation of multiwalled carbon nanotubes on the adsorption affinity and capacity of polar and nonpolar organic compounds in aqueous phase. Environ Sci Technol, 2012, 46(10): 5446-5454.
- 26. Kang ES, Kim DS, Suhito IR, et al. Guiding osteogenesis of mesenchymal stem cells using carbon-based nanomaterials. Nano Converg, 2017, 4(1): 2.
- 27. Gupta A, Woods MD, Illingworth KD, et al. Single walled carbon nanotube composites for bone tissue engineering. J Orthop Res, 2013, 31(9): 1374-1381.
- 28. Kiran S, Nune KC, Misra RD. The significance of grafting collagen on polycaprolactone composite scaffolds: processing-structure-functional property relationship. J Biomed Mater Res A, 2015, 103(9): 2919-2931.
- 29. Cirillo G, Hampel S, Spizzirri UG, et al. Carbon nanotubes hybrid hydrogels in drug delivery: A perspective review. Biomed Res, 2014, 2014: 825017.
- 30. Usui Y, Aoki K, Narita N, et al. Carbon nanotubes with high bone-tissue compatibility and bone-formation acceleration effects. Small, 2008, 4(2): 240-246.
- 31. La WG, Jin M, Park S, et al. Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for bone regeneration. Int J Nanomedicine, 2014, 9 Suppl 1(Suppl 1): 107-116.
- 32. Murugan E, Arumugam S. New dendrimer functionalized multi-walled carbon nanotube hybrids for bone tissue engineering. RSC Adv, 2014, 4: 35428-35441.
- 33. Li Z, de Barros ALB, Soares DCF, et al. Functionalized single-walled carbon nanotubes: cellular uptake, biodistribution and applications in drug delivery. Int J Pharm, 2017, 524(1-2): 41-54.
- 34. Sahoo NG, Pan YZ, Li L, et al. Nanocomposites for bone tissue regeneration. Nanomedicine (Lond), 2013, 8(4): 639-653.
- 35. Munir KS, Wen C, Li Y. Carbon nanotubes and graphene as nanoreinforcements in metallic biomaterials: A review. Adv Biosyst, 2019, 3: 2366-7478.
- 36. Kim HW. Biomedical nanocomposites of hydroxyapatite/polycaprolactone obtained by surfactant mediation. J Biomed Mater Res A, 2007, 83(1): 169-177.
- 37. Neubauer E, Kitzmantel M, Hulman M, et al. Potential and challenges of metal-matrix-composites reinforced with carbon nanofibers and carbon nanotubes. Compos Sci Technol, 2010, 70(16): 2228-2236.
- 38. 肖镇昆, 吴磊, 米饶, 等. 碳纳米管对羟基磷灰石基复合材料力学性能的影响. 无机化学学报, 2015, 31(1): 114-120.
- 39. Qian D, Dickey EC, Andrew R, et al. Load transfer and deformation mechanisms in carbon nanotube-polystyrene composites. Appl Phys Lett, 2000, 76: 2868-2870.
- 40. Newman P, Minett A, Ellis-Behnke R, et al. Carbon nanotubes: their potential and pitfalls for bone tissue regeneration and engineering. Nanomedicine, 2013, 9(8): 1139-1158.
- 41. Maiti D, Tong XM, Mou XZ, et al. Carbon-based nanomaterials for biomedical applications: A recent study. Front Pharmacol, 2019, 9: 1401.
- 42. Lee WC, Lim CH, Kenry N, et al. Cell-assembled graphene biocomposite for enhanced chondrogenic differentiation. Small, 2015, 11(8): 963-969.
- 43. Ferrer-Anglada N, Gomis V, El-Hachemi Z, et al. Carbon nanotube based composites for electronic applications: CNT-conducting polymers, CNT-Cu. Phys Status Solidi, 2010, 203(6): 1082-1087.
- 44. Saha A, Jiang C, Martí AA. Carbon nanotube networks on different platforms. Carbon, 2014, 79: 1-18.
- 45. Shanta AS, Al Mamun KA, Islam SK, et al. Carbon nanotubes, nanofibers and nanospikes for electrochemical sensing: A review. Int High Speed Electron Syst, 2017, 26(3): 25-36.
- 46. Mercante LA, Pavinatto A, Iwaki LE, et al. Electrospun polyamide 6/poly(allylamine hydrochloride) nanofibers functionalized with carbon nanotubes for electrochemical detection of dopamine. ACS Appl Mater Interfaces, 2015, 7(8): 4784-4790.
- 47. Mackle JN, Blond DJ, Mooney E, et al. In vitro characterization of an electroactive carbon-nanotube-based nanofiber scaffold for tissue engineering. Macromol Biosci, 2011, 11(9): 1272-1282.
- 48. Cunha C, Panseri S, Iannazzo D, et al. Hybrid composites made of multiwalled carbon nanotubes functionalized with Fe3O4 nanoparticles for tissue engineering applications. Nanotechnol, 2012, 23(46): 465102.
- 49. Kaur T, Kulanthaivel S, Arunachalam T, et al. Biological and mechanical evaluation of poly(lactic-co-glycolic acid) based composites reinforced with one, two and three dimensional carbon biomaterials for bone tissue regeneration. Biomed Mater, 2017, 12(2): 025012.
- 50. Díaz E, Puerto I, Sandonis I, et al. Hydrolytic degradation and cytotoxicity of poly(lactic-co-glycolic acid)/multiwalled carbon nanotubes for bone regeneration. Appl Polym Sci, 2020, 137(10): 48439.
- 51. Elgrabli D, Dachraoui W, Ménard-Moyon C, et al. Carbon nanotube degradation in macrophages: live nanoscale monitoring and understanding of biological pathway. ACS Nano, 2015, 9(10): 10113-10124.
- 52. Takanashi S, Hara K, Aoki K, et al. Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice. Sci Rep, 2012, 2: 498.
- 53. Nomura H, Takanashi S, Tanaka M, et al. Specific biological responses of the synovial membrane to carbon nanotubes. Sci Rep, 2015, 5: 14314.
- 54. Sobajima A, Haniu H, Nomura H, et al. Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice. Int J Nanomedicine, 2019, 14: 6465-6480.
- 55. Yang ST, Wang X, Jia G, et al. Long-term accumulation and low toxicity of single-walled carbon nanotubes in intravenously exposed mice. Toxicol Lett, 2008, 181(3): 182-189.
- 56. Yang Z, Zhang Y, Yang Y, et al. Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomedicine, 2010, 6(3): 427-441.
- 57. Murakami T, Ajima K, Miyawaki J, et al. Drug-loaded carbon nanohorns: adsorption and release of dexamethasone in vitro. Mol Pharm, 2004, 1(6): 399-405.
- 58. Bianco A, Kostarelos K, Prato M. Opportunities and challenges of carbon-based nanomaterials for cancer therapy. Expert Opin Drug Deliv, 2008, 5(3): 331-342.
- 59. Sukhodub LB, Sukhodub LF, Prylutskyy YI, et al. Composite material based on hydroxyapatite and multi-walled carbon nanotubes filled by iron: Preparation, properties and drug release ability. Mater Sci Eng C Mater Biol Appl, 2018, 93: 606-614.
- 60. Bhirde AA, Patel S, Sousa AA, et al. Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice. Nanomedicine (Lond), 2010, 5(10): 1535-1546.
- 61. Kam NW, O’Connell M, Wisdom JA, et al. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc Natl Acad Sci U S A, 2005, 102(33): 11600-11605.
- 62. Kamalha E, Shi XY, Mwasiagi JI, et al. Nanotechnology and carbon nanotubes; A review of potential in drug delivery. Macromol Res, 2012, 20: 891-898.
- 63. Vankoningsloo S, Piret JP, Saout C, et al. Cytotoxicity of multi-walled carbon nanotubes in three skin cellular models: effects of sonication, dispersive agents and corneous layer of reconstructed epidermis. Nanotoxicology, 2010, 4(1): 84-97.
- 64. Mukherjee S, Nandi SK, Kundu B, et al. Enhanced bone regeneration with carbon nanotube reinforced hydroxyapatite in animal model. J Mech Behav Biomed Mater, 2016, 60: 243-255.
- 65. Mirjalili F, Mohammadi H, Azimi M, et al. Synthesis and characterization of β-TCP/CNT nanocomposite: Morphology, microstructure and in vitro bioactivity. Ceramics International, 2017, 43(10): 7573-7580.
- 66. Metoki N, Rosa CMR, Zanin H, et al. Electrodeposition and biomineralization of nano-beta-tricalcium phosphate on graphenated carbon nanotubes. Surface & Coatings Technology, 2016, 297: 51-57.
- 67. Shrestha Sita, Shrestha BK, Ko SW, et al. Engineered cellular microenvironments from functionalized multiwalled carbon nanotubes integrating Zein/Chitosan@Polyurethane for bone cell regeneration. Carbohydrate Polymers, 2020, 251: 117035.
- 68. Carson L, Kelly-Brown C, Stewart M, et al. Synthesis and characterization of chitosan-carbon nanotube composites. Mater Lett, 2009, 63(6-7): 617-620.
- 69. Hirata E, Uo M, Takita H, et al. Multiwalled carbon nanotube-coating of 3D collagen scaffolds for bone tissue engineering. Carbon, 2011, 49(10): 3284-3291.
- 70. Meng Z, He JK, Xia ZX, et al. Fabrication of microfibrous PCL/MWCNTs scaffolds via melt-based electrohydrodynamic printing. Materials Letters, 2020, 278(1): 128440.
- 71. Swietek M, Broz A, Tarasiuk J, et al. Carbon nanotube/iron oxide hybrid particles and their PCL-based 3D composites for potential bone regeneration. Materials Science and Engineering: C, 2019, 104: 109913.
- 72. Kołodziej A, Wesełucha-Birczyńska A, Świętek M, et al. A 2D-Raman correlation spectroscopy study of the interaction of the polymer nanocomposites with carbon nanotubes and human osteoblast-like cells interface. Journal of Molecular Structure, 2020, 1212: 128135.
- 73. De Moura NK, Martins EF, Oliveira RLMS, et al. Synergistic effect of adding bioglass and carbon nanotubes on poly (lactic acid) porous membranes for guided bone regeneration. Materials Science and Engineering: C, 2020, 117: 111327.
- 74. Seligra PG, Nuevo F, Lamanna M, et al. Covalent grafting of carbon nanotubes to PLA in order to improve compatibility. Composites Part B: Engineering, 2013, 46: 61-68.
- 75. 原伟. 功能性碳纳米管的制备及其在活体内组织分布和代谢的初步研究. 太原: 山西医科大学, 2008.
- 76. Wang JT, Fabbro C, Venturelli E, et al. The relationship between the diameter of chemically-functionalized multi-walled carbon nanotubes and their organ biodistribution profiles in vivo. Biomaterials, 2014, 35(35): 9517-9528.
- 77. Lacerda L, Ali-Boucetta H, Herrero MA, et al. Tissue histology and physiology following intravenous administration of different types of functionalized multiwalled carbon nanotubes. Nanomedicine (Lond), 2008, 3(2): 149-161.
- 78. Kolosnjaj-Tabi J, Hartman KB, Boudjemaa S, et al. In vivo behavior of large doses of ultrashort and full-length single-walled carbon nanotubes after oral and intraperitoneal administration to Swiss mice. ACS Nano, 2010, 4(3): 1481-1492.
- 79. Lacerda L, Herrero MA, Venner K, et al. Carbon-nanotube shape and individualization critical for renal excretion. Small, 2008, 4(8): 1130-1132.
- 80. Haniu H, Saito N, Matsuda Y, et al. Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells. Int J Nanomedicine, 2014, 9: 1979-1990.
- 81. Sargent LM, Reynolds SH, Castranova V. Potential pulmonary effects of engineered carbon nanotubes: in vitro genotoxic effects. Nanotoxicology, 2010, 4: 396-408.
- 82. Naya M, Kobayashi N, Mizuno K, et al. Evaluation of the genotoxic potential of single-wall carbon nanotubes by using a battery of in vitro and in vivo genotoxicity assays. Regul Toxicol Pharmacol, 2011, 61(2): 192-198.
- 83. Magrez A, Kasas S, Salicio V, et al. Cellular toxicity of carbon-based nanomaterials. Nano Lett, 2006, 6(6): 1121-1125.
- 84. Jacobsen NR, Pojana G, White P, et al. Genotoxicity, cytotoxicity, and reactive oxygen species induced by single-walled carbon nanotubes and C(60) fullerenes in the FE1-Mutatrade markMouse lung epithelial cells. Environ Mol Mutagen, 2008, 49(6): 476-487.
- 85. Di Sotto A, Chiaretti M, Carru GA, et al. Multi-walled carbon nanotubes: Lack of mutagenic activity in the bacterial reverse mutation assay. Toxicol Lett, 2009, 184(3): 192-197.
- 86. Lewinski N, Colvin V, Drezek, R, et al. Cytotoxicity of nanoparticles. Small, 2009, 4(1): 26-49.
- 87. Sharma S, Naskar S, Kuotsu, K. A review on carbon nanotubes: Influencing toxicity and emerging carrier for platinum based cytotoxic drug application. Drug Deliv Sci Technolo, 2019, 51: 708-720.
- 88. Che Abdullah CA, Azad CL, Ovalle-Robles R, et al. Primary liver cells cultured on carbon nanotube substrates for liver tissue engineering and drug discovery applications. ACS Appl Mater Interfaces, 2014, 6(13): 10373-10380.
- 89. Yu HY, Yao JM, Qin ZY, et al. Comparison of covalent and noncovalent interactions of carbon nanotubes on the crystallization behavior and thermal properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate). Appl Polym Sci, 2013, 130(6): 4299-4307.
- 90. Haniu H, Saito N, Matsuda Y, et al. Effect of dispersants of multi-walled carbon nanotubes on cellular uptake and biological responses. Int J Nanomedicine, 2011, 6: 3295-3307.
- 91. Nazeri Niloofar, Derakhashan MA, Fardi-Majidi A, et al. Novel electro-conductive nanocomposites based on electrospun PLGA/CNT for biomedical applications. Journal of Materials Science Materials in Medicine, 2018, 29: 168.
- 92. Niroula J, Premaratne G, Ali Shojaee S, et al. Combined covalent and noncovalent carboxylation of carbon nanotubes for sensitivity enhancement of clinical immunosensors. Chem Commun (Camb), 2016, 52(88): 13039-13042.
- 93. Usrey ML, Strano MS. Controlling single-walled carbon nanotube surface adsorption with covalent and noncovalent functionalization. Phys Chem C, 2009, 113: 12443-12453.
- 94. Rezvova MA, Yuzhalin AE, Glushkova TV, et al. Biocompatible nanocomposites based on poly(styrene-block-isobutylene-block-styrene) and carbon nanotubes for biomedical application. Polymers, 2020, 12(9): 2158.