Issue

Vol. 13 (2021)

Nb2C MXene-Functionalized Scaffolds Enables Osteosarcoma Phototherapy and Angiogenesis/Osteogenesis of Bone Defects

https://doi.org/10.1007/s40820-020-00547-6
Junhui Yin
Institute of Microsurgery On Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China
Shanshan Pan
School of Life Sciences, Shanghai University, Shanghai 200444, People’s Republic of China
Xiang Guo
Department of Orthopedics, The Second Affiliated Hospital, The Navy Medical University, Shanghai 200003, People’s Republic of China
Youshui Gao
Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China
Daoyu Zhu
Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China
Qianhao Yang
Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China
Junjie Gao
Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China
Changqing Zhang
Institute of Microsurgery On Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China
Yu Chen
School of Life Sciences, Shanghai University, Shanghai 200444, People’s Republic of China

Corresponding Author: Yu Chen

chenyuedu@shu.edu.cn

Nano-Micro Letters, Vol. 13 (2021), Article Number: 30

Abstract

Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor, but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site. In this work, we report a rational integration of photonic-responsive two-dimensional (2D) ultrathin niobium carbide (Nb2C) MXene nanosheets (NSs) into the 3D-printed bone-mimetic scaffolds (NBGS) for osteosarcoma treatment. The integrated 2D Nb2C-MXene NSs feature specific photonic response in the second near-infrared (NIR-II) biowindow with high tissue-penetrating depth, making it highly efficient in killing bone cancer cells. Importantly, Nb-based species released by the biodegradation of Nb2C MXene can obviously promote the neogenesis and migration of blood vessels in the defect site, which can transport more oxygen, vitamins and energy around the bone defect for the reparative process, and gather more immune cells around the defect site to accelerate the degradation of NBGS. The degradation of NBGS provides sufficient space for the bone remodeling. Besides, calcium and phosphate released during the degradation of the scaffold can promote the mineralization of new bone tissue. The intrinsic multifunctionality of killing bone tumor cell and promoting angiogenesis and bone regeneration makes the engineered Nb2C MXene-integrated composite scaffolds a distinctive implanting biomaterial on the efficient treatment of bone tumor.


Highlights:


1 2D Nb2C MXene-integrated 3D-printing scaffolds against osteosarcoma were constructed with theragenerative functionality.
2 Nb2C MXene in 3D scaffolds enabled photothermal ablation of osteosarcoma at NIR-II biowindow.
3 Nb2C MXene in 3D scaffolds promoted osteogenesis, osteoconduction and osteoinduction, and drove vascularization for bone regeneration.

Keywords

Nb2C MXene 3D printing Phototherapy Osteosarcoma Vascularization
Yin, Junhui, Shanshan Pan, Xiang Guo, Youshui Gao, Daoyu Zhu, Qianhao Yang, Junjie Gao, Changqing Zhang, and Yu Chen. 2021. “Nb2C MXene-Functionalized Scaffolds Enables Osteosarcoma Phototherapy and Angiogenesis/Osteogenesis of Bone Defects”. Nano-Micro Letters 13 (January):30. https://doi.org/10.1007/s40820-020-00547-6.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. E. Ward, C. DeSantis, A. Robbins, B. Kohler, A. Jemal, Childhood and adolescent cancer statistics. CA Cancer J. Clin. 64(2), 83–103 (2014). https://doi.org/10.3322/caac.21219
  2. D. Heymann, Metastatic osteosarcoma challenged by regorafenib. Lancet. Oncol. 20(1), 12–14 (2019). https://doi.org/10.1016/s1470-2045(18)30821-0
  3. F. Duffaud, O. Mir, P. Boudou-Rouquette, S. Piperno-Neumann, N. Penel et al., Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study. Lancet. Oncol. 20(1), 120–133 (2019). https://doi.org/10.1016/s1470-2045(18)30742-3
  4. Y. Wang, J. Wang, H. Hao, M. Cai, S. Wang et al., In vitro and in vivo mechanism of bone tumor inhibition by selenium-doped bone mineral nanoparticles. ACS Nano 10(11), 9927–9937 (2016). https://doi.org/10.1021/acsnano.6b03835
  5. R.J. Grimer, Surgical options for children with osteosarcoma. Lancet. Oncol. 6(2), 85–92 (2005). https://doi.org/10.1016/S1470-2045(05)01734-1
  6. E.D. Arrington, W.J. Smith, H.G. Chambers, A.L. Bucknell, N.A. Davino, Complications of iliac crest bone graft harvesting. Clin. Orthop. Relat. Res. 329, 300–309 (1996). https://doi.org/10.1097/00003086-199608000-00037
  7. C.G. Finkemeier, Bone-grafting and bone-graft substitutes. J. Bone. Joint. Surg. Am. 84(3), 454–464 (2002). https://doi.org/10.2106/00004623-200203000-00020
  8. C. Mauffrey, B.T. Barlow, W. Smith, Management of segmental bone defects. J. Am. Acad. Orthop. Surg. 23(3), 143–153 (2015). https://doi.org/10.5435/JAAOS-D-14-00018
  9. A. Ho-Shui-Ling, J. Bolander, L.E. Rustom, A.W. Johnson, F.P. Luyten et al., Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials 180, 143–162 (2018). https://doi.org/10.1016/j.biomaterials.2018.07.017
  10. M. Vallet-Regi, E. Ruiz-Hernandez, Bioceramics: from bone regeneration to cancer nanomedicine. Adv. Mater. 23(44), 5177–5218 (2011). https://doi.org/10.1002/adma.201101586
  11. S. Quader, K. Kataoka, Nanomaterial-enabled cancer therapy. Mol. Ther. 25(7), 1501–1513 (2017). https://doi.org/10.1016/j.ymthe.2017.04.026
  12. X. Wang, T. Li, H. Ma, D. Zhai, C. Jiang et al., A 3D-printed scaffold with MoS2 nanosheets for tumor therapy and tissue regeneration. NPG Asia. Mater. 9(4), 376 (2017). https://doi.org/10.1038/am.2017.47
  13. Q. Yu, Y. Han, T. Tian, Q. Zhou, Z. Yi et al., Chinese sesame stick-inspired nano-fibrous scaffolds for tumor therapy and skin tissue reconstruction. Biomaterials 194, 25–35 (2019). https://doi.org/10.1016/j.biomaterials.2018.12.012
  14. H. Ma, J. Luo, Z. Sun, L. Xia, M. Shi et al., 3D printing of biomaterials with mussel-inspired nanostructures for tumor therapy and tissue regeneration. Biomaterials 111, 138–148 (2016). https://doi.org/10.1016/j.biomaterials.2016.10.005
  15. B. Yang, J. Yin, Y. Chen, S. Pan, H. Yao et al., 2D black phosphorus reinforced 3D printed scaffolds: a stepwise countermeasure for osteosarcoma. Adv. Mater. 30(10), 1705611 (2018). https://doi.org/10.1002/adma.201705611
  16. H. Lin, S. Gao, C. Dai, Y. Chen, J. Shi, A two-dimensional biodegradable niobium carbide (MXene) for photothermal tumor eradication in NIR-I and NIR-II biowindows. J. Am. Chem. Soc. 139(45), 16235–16247 (2017). https://doi.org/10.1021/jacs.7b07818
  17. H. Lin, Y. Wang, S. Gao, Y. Chen, J. Shi, Theranostic 2D tantalum carbide (MXene). Adv. Mater. 30(4), 1703284 (2018). https://doi.org/10.1002/adma.201703284
  18. X. Han, X. Jing, D. Yang, H. Lin, Z. Wang et al., Therapeutic mesopore construction on 2D Nb2C MXenes for targeted and enhanced chemo-photothermal cancer therapy in NIR-II biowindow. Theranostics 8(16), 4491–4508 (2018). https://doi.org/10.7150/thno.26291
  19. Y. Zhang, L. Xia, D. Zhai, M. Shi, Y. Luo et al., Mesoporous bioactive glass nanolayer-functionalized 3D-printed scaffolds for accelerating osteogenesis and angiogenesis. Nanoscale 7(45), 19207–19221 (2015). https://doi.org/10.1039/c5nr05421d
  20. M. Zhu, K. Li, Y. Zhu, J. Zhang, X. Ye, 3D-printed hierarchical scaffold for localized isoniazid/rifampin drug delivery and osteoarticular tuberculosis therapy. Acta Biomater. 16, 145–155 (2015). https://doi.org/10.1016/j.actbio.2015.01.034
  21. S. Zhao, J. Zhang, M. Zhu, Y. Zhang, Z. Liu et al., Three-dimensional printed strontium-containing mesoporous bioactive glass scaffolds for repairing rat critical-sized calvarial defects. Acta Biomater. 12, 270–280 (2015). https://doi.org/10.1016/j.actbio.2014.10.015
  22. D.S. Brauer, Bioactive glasses-structure and properties. Angew. Chem. Int. Ed. 54(14), 4160–4181 (2015). https://doi.org/10.1002/anie.201405310
  23. D.W. Losordo, S. Dimmeler, Therapeutic angiogenesis and vasculogenesis for ischemic disease. Part I: Angiogenic Cytokines. Circulation 109(21), 2487–2491 (2004). https://doi.org/10.1161/01.CIR.0000128595.79378.FA
  24. G.W. Hu, Q. Li, X. Niu, B. Hu, J. Liu et al., Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice. Stem. Cell Res. Ther. 6, 10 (2015). https://doi.org/10.1186/scrt546
  25. J. Yin, J. Yu, Q. Ke, Q. Yang, D. Zhu et al., La-doped biomimetic scaffolds facilitate bone remodelling by synchronizing osteointegration and phagocytic activity of macrophages. J. Mater. Chem. B 7, 3066–3074 (2019). https://doi.org/10.1039/c8tb03244k
  26. O.D. Leaffer, S. Gupta, M.W. Barsoum, J.E. Spanier, On the Raman scattering from selected M2AC compounds. J. Mater. Res. 22(10), 2651–2654 (2007). https://doi.org/10.1557/JMR.2007.0376
  27. A.L. Antaris, H. Chen, K. Cheng, Y. Sun, G. Hong et al., A small-molecule dye for NIR-II imaging. Nat. Mater. 15(2), 235–242 (2016). https://doi.org/10.1038/nmat4476
  28. R. Vankayala, K.C. Hwang, Near-infrared-light-activatable nanomaterial-mediated phototheranostic nanomedicines: an emerging paradigm for cancer treatment. Adv. Mater. 30(23), 1706320 (2018). https://doi.org/10.1002/adma.201706320
  29. L. Xue, W. Xie, L. Driessen, K.F. Domke, Y. Wang et al., Advanced SERS sensor based on capillarity-assisted preconcentration through gold nanoparticle-decorated porous nanorods. Small 13(22), 1603947 (2017). https://doi.org/10.1002/smll.201603947
  30. Z. Xie, D. Wang, T. Fan, C. Xing, Z. Li et al., Black phosphorus analogue tin sulfide nanosheets: synthesis and application as near-infrared photothermal agents and drug delivery platforms for cancer therapy. J. Mater. Chem. B 6(29), 4747–4755 (2018). https://doi.org/10.1039/c8tb00729b
  31. W. Dang, B. Ma, Z. Huan, R. Lin, X. Wang et al., LaB6 surface chemistry-reinforced scaffolds for treating bone tumors and bone defects. Appl. Mater. Today 16, 42–55 (2019). https://doi.org/10.1016/j.apmt.2019.04.015
  32. H. Ma, T. Li, Z. Huan, M. Zhang, Z. Yang et al., 3D printing of high-strength bioscaffolds for the synergistic treatment of bone cancer. NPG Asia Mater. 10(4), 31–44 (2018). https://doi.org/10.1038/s41427-018-0015-8
  33. W. Dang, T. Li, B. Li, H. Ma, D. Zhai et al., A bifunctional scaffold with CuFeSe2 nanocrystals for tumor therapy and bone reconstruction. Biomaterials 160, 92–106 (2018). https://doi.org/10.1016/j.biomaterials.2017.11.020
  34. T. Fan, Animal models of osteosarcoma. Exp. Rev. Antica. Ther. 10(8), 1327–1338 (2010). https://doi.org/10.1586/era.10.107
  35. C. Martin, K. Kostarelos, M. Prato, A. Bianco, Biocompatibility and biodegradability of 2D materials: graphene and beyond. Chem. Commun. 55(39), 5540–5546 (2019). https://doi.org/10.1039/c9cc01205b
  36. A. Marrella, T.Y. Lee, D.H. Lee, S. Karuthedom, D. Syla et al., Engineering vascularized and innervated bone biomaterials for improved skeletal tissue regeneration. Mater. Today 21(4), 362–376 (2018). https://doi.org/10.1016/j.mattod.2017.10.005
  37. J. Schmid, B. Wallkamm, C.H. Hammerle, S. Gogolewski, N.P. Lang, The significance of angiogenesis in guided bone regeneration. A case report of a rabbit experiment. Clini. Oral Impl. Res. 8(3), 244–248 (1997). https://doi.org/10.1034/j.1600-0501.1997.080311.x
  38. A.S. Chung, J. Lee, N. Ferrara, Targeting the tumour vasculature: insights from physiological angiogenesis. Nat. Rev. Cancer 10(7), 505–514 (2010). https://doi.org/10.1038/nrc2868
  39. D.H. Kempen, L. Lu, A. Heijink, T.E. Hefferan, L.B. Creemers et al., Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials 30(14), 2816–2825 (2009). https://doi.org/10.1016/j.biomaterials.2009.01.031
  40. T.A. Einhorn, L.C. Gerstenfeld, Fracture healing: mechanisms and interventions. Nat. Rev. Rheumatol. 11(1), 45–54 (2015). https://doi.org/10.1038/nrrheum.2014.164
  41. M.A. Saghiri, J. Orangi, A. Asatourian, C.M. Sorenson, N. Sheibani, Functional role of inorganic trace elements in angiogenesis part III: (Ti, Li, Ce, As, Hg, Va, Nb and Pb). Crit. Rev. Oncol. Hematol. 98, 290–301 (2016). https://doi.org/10.1016/j.critrevonc.2015.10.004
  42. V.M. Pacheco, D. de Ligny, J. Schmidt, R. Detsch, A.R. Boccaccini, Development and characterization of niobium-releasing silicate bioactive glasses for tissue engineering applications. J. Eur. Ceram. Soc. 38(3), 871–876 (2018)
  43. H.J. Park, Y.L. Zhang, S.P. Georgescu, K.L. Johnson, D.Q. Kong et al., Human umbilical vein endothelial cells and human dermal microvascular endothelial cells offer new insights into the relationship between lipid metabolism and angiogenesis. Stem. Cell. Rev. 2(2), 93–101 (2006). https://doi.org/10.1007/s12015-006-0015-x
  44. A. Sobolev, A. Valkov, A. Kossenko, I. Wolicki, M. Zinigrad et al., Bioactive coating on Ti alloy with high osseointegration and antibacterial Ag nanoparticles. ACS Appl. Mater. Interfaces 11(43), 39534–39544 (2019). https://doi.org/10.1021/acsami.9b13849
  45. N. Huebsch, E. Lippens, K. Lee, M. Mehta, S.T. Koshy et al., Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation. Nat. Mater. 14(12), 1269–1277 (2015). https://doi.org/10.1038/nmat4407
  46. A.L. Carlson, C.A. Florek, J.J. Kim, T. Neubauer, J.C. Moore et al., Microfibrous substrate geometry as a critical trigger for organization, self-renewal, and differentiation of human embryonic stem cells within synthetic 3-dimensional microenvironments. FASEB J. 26(8), 3240–3251 (2012). https://doi.org/10.1096/fj.11-192732
  47. L.J. Nesti, W.M. Jackson, R.M. Shanti, S.M. Koehler, A.B. Aragon et al., Differentiation potential of multipotent progenitor cells derived from war-traumatized muscle tissue. J. Bone. Joint. Surg. Am. 90(11), 2390–2398 (2008). https://doi.org/10.2106/jbjs.h.00049
  48. F.B. Wydra, P.J. York, A.F. Vidal, Allografts: Osteochondral, shell, and paste. Clin. Sports Med. 36(3), 509–523 (2017). https://doi.org/10.1016/j.csm.2017.02.007
  49. W. Liu, Y. Wei, X. Zhang, M. Xu, X. Yang et al., Lower extent but similar rhythm of osteogenic behavior in hBMSCs cultured on nanofibrous scaffolds versus induced with osteogenic supplement. ACS Nano 7(8), 6928–6938 (2013). https://doi.org/10.1021/nn402118s
  50. J. Yang, J. Zhang, C. Ding, D. Dong, P. Shang, Regulation of osteoblast differentiation and iron content in MC3T3-E1 cells by static magnetic field with different intensities. Biol. Tra. Elem. Res. 184(1), 214–225 (2018). https://doi.org/10.1007/s12011-017-1161-5
  51. Q. Yang, H. Yin, T. Xu, D. Zhu, J. Yin et al., Engineering 2D mesoporous Silica@MXene-Integrated 3D-printing scaffolds for combinatory osteosarcoma therapy and NO-augmented bone regeneration. Small 16(14), 1906814 (2019). https://doi.org/10.1002/smll.201906814
  52. S. Pan, J. Yin, L. Yu, C. Zhang, Y. Zhu et al., 2D MXene-integrated 3D-printing scaffolds for augmented osteosarcoma phototherapy and accelerated tissue reconstruction. Adv. Sci. 72(2), 1901511 (2019). https://doi.org/10.1002/advs.201901511
  53. X. Fu, Y. Li, T. Huang, Z. Yu, K. Ma et al., Runx2/Osterix and zinc uptake synergize to orchestrate osteogenic differentiation and citrate containing bone apatite formation. Adv. Sci. 5(4), 1700755 (2018). https://doi.org/10.1002/advs.201700755
  54. S. Lin, G. Yang, F. Jiang, M. Zhou, S. Yin et al., A magnesium-enriched 3D culture system that mimics the bone development microenvironment for vascularized bone regeneration. Adv. Sci. 6(12), 1900209 (2019). https://doi.org/10.1002/advs.201900209
  55. H.A. Rather, D. Jhala, R. Vasita, Dual functional approaches for osteogenesis coupled angiogenesis in bone tissue engineering. Mater. Sci. Eng. C: Mater. Biol. Appl. 103, 109761 (2019). https://doi.org/10.1016/j.msec.2019.109761
Read More
Author biographies are not available.
Download this PDF file
PDF SUPPLEMENTARY MATERIAL
Statistic
Read Counter : 6820 Download : 5128

Most read articles by the same author(s)