Skip to main content

The Development of Extracellular Vesicle-Integrated Biomaterials for Bone Regeneration

  • Chapter
  • First Online:
Biomimicked Biomaterials

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1250))

Abstract

The clinical need for effective bone regeneration remains in huge demands. Although autologous and allogeneic bone grafts are generally considered “gold standard” treatments for bone defects, these approaches may result in various complications. Furthermore, safety considerations of gene- and cell-based therapies require further clarification and approval from regulatory authorities. Therefore, developing new therapeutic biomaterials that can empower endogenous regenerative properties to accelerate bone repair and regeneration is of great significance. Extracellular vesicles (EVs) comprise a heterogeneous population of naturally derived nanoparticles that play a critical role in mediating cell–cell communication. The vast amount of biological processes that EVs are involved in, such as immune modulation, senescence, and angiogenesis, and the versatility of manner in which they can influence the behavior of recipient cells make EVs an interesting source for both diagnostic and therapeutic applications. Advancement of knowledge in the fields of immunology and cell biology has sparked the exploration of the potential of EVs in the field of regenerative medicine. EVs travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating the recruitment, proliferation, and differentiation of recipient cells. Numerous studies have demonstrated the pivotal role of EVs in tissue regeneration both in vitro and in vivo. In this chapter, we will outline current knowledge surrounding EVs, summarize their functional roles in bone regenerative medicine, and elaborate on potential application and challenges of EV-integrated biomaterials in bone tissue engineering.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Thery C, Witwer KW, Aikawa E et al (2018) Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the international society for extracellular vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 7(1):1535750

    Article  PubMed  PubMed Central  Google Scholar 

  2. Chargaff E, West R (1946) The biological significance of the thromboplastic protein of blood. J Biol Chem 166(1):189–197

    Article  CAS  PubMed  Google Scholar 

  3. Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13(3):269–288

    Article  CAS  PubMed  Google Scholar 

  4. Anderson HC (1967) Electron microscopic studies of induced cartilage development and calcification. J Cell Biol 35(1):81–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bonucci E (1967) Fine structure of early cartilage calcification. J Ultrastruct Res 20(1):33–50

    Article  CAS  PubMed  Google Scholar 

  6. Trams EG, Lauter CJ, Salem N et al (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 645(1):63–70

    Article  CAS  PubMed  Google Scholar 

  7. Taylor DD, Homesley HD, Doellgast GJ (1980) Binding of specific peroxidase-labeled antibody to placental-type phosphatase on tumor-derived membrane fragments. Cancer Res 40(11):4064–4069

    CAS  PubMed  Google Scholar 

  8. Dvorak HF, Quay SC, Orenstein NS et al (1981) Tumor shedding and coagulation. Science 212(4497):923–924

    Article  CAS  PubMed  Google Scholar 

  9. Harding C, Heuser J, Stahl P (1983) Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 97(2):329–339

    Article  CAS  PubMed  Google Scholar 

  10. Pan BT, Johnstone RM (1983) Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33(3):967–978

    Article  CAS  PubMed  Google Scholar 

  11. Harding C, Heuser J, Stahl P (1984) Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding. Eur J Cell Biol 35(2):256–263

    CAS  PubMed  Google Scholar 

  12. Johnstone RM, Adam M, Hammond JR et al (1987) Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 262(19):9412–9420

    Article  CAS  PubMed  Google Scholar 

  13. Raposo G, Nijman HW, Stoorvogel W et al (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183(3):1161–1172

    Article  CAS  PubMed  Google Scholar 

  14. Zitvogel L, Regnault A, Lozier A et al (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4(5):594–600

    Article  CAS  PubMed  Google Scholar 

  15. Thery C, Duban L, Segura E et al (2002) Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nat Immunol 3(12):1156–1162

    Article  CAS  PubMed  Google Scholar 

  16. Skog J, Wurdinger T, van Rijn S et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Park JE, Tan HS, Datta A et al (2010) Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Proteomics 9(6):1085–1099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zomer A, Maynard C, Verweij FJ et al (2015) In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell 161(5):1046–1057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lane RE, Korbie D, Hill MM et al (2018) Extracellular vesicles as circulating cancer biomarkers: opportunities and challenges. Clin Transl Med 7(1):14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Valadi H, Ekstrom K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659

    Article  CAS  PubMed  Google Scholar 

  21. Ratajczak J, Miekus K, Kucia M et al (2006) Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20(5):847–856

    Article  CAS  PubMed  Google Scholar 

  22. Cho E, Nam GH, Hong Y et al (2018) Comparison of exosomes and ferritin protein nanocages for the delivery of membrane protein therapeutics. J Control Release 279:326–335

    Article  CAS  PubMed  Google Scholar 

  23. Liu M, Sun Y, Zhang Q (2018) Emerging role of extracellular vesicles in bone remodeling. J Dent Res 97(8):859–868

    Article  CAS  PubMed  Google Scholar 

  24. Hao ZC, Lu J, Wang SZ et al (2017) Stem cell-derived exosomes: a promising strategy for fracture healing. Cell Prolif 50(5). https://doi.org/10.1111/cpr.12359

  25. Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200(4):373–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Borges FT, Reis LA, Schor N (2013) Extracellular vesicles: structure, function, and potential clinical uses in renal diseases. Braz J Med Biol Res 46(10):824–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang Y, Chen X, Gueydan C et al (2018) Plasma membrane changes during programmed cell deaths. Cell Res 28(1):9–21

    Article  CAS  PubMed  Google Scholar 

  28. Hauser P, Wang S, Didenko VV (2017) Apoptotic bodies: selective detection in extracellular vesicles. Methods Mol Biol 1554:193–200

    Article  CAS  PubMed  Google Scholar 

  29. Wang X, Omar O, Vazirisani F et al (2018) Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation. PLoS One 13(2):e0193059

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Squillaro T, Peluso G, Galderisi U (2016) Clinical trials with mesenchymal stem cells: an update. Cell Transplant 25(5):829–848

    Article  PubMed  Google Scholar 

  31. von Bahr L, Batsis I, Moll G et al (2012) Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cell 30(7):1575–1578

    Article  CAS  Google Scholar 

  32. De Jong OG, Van Balkom BW, Schiffelers RM et al (2014) Extracellular vesicles: potential roles in regenerative medicine. Front Immunol 5:608

    PubMed  PubMed Central  Google Scholar 

  33. Harding C, Stahl P (1983) Transferrin recycling in reticulocytes: pH and iron are important determinants of ligand binding and processing. Biochem Biophys Res Commun 113(2):650

    Article  CAS  PubMed  Google Scholar 

  34. Zaborowski MP, Balaj L, Breakefield XO et al (2015) Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience 65(8):783–797

    Article  PubMed  PubMed Central  Google Scholar 

  35. Maas SLN, Breakefield XO, Weaver AM (2017) Extracellular vesicles: unique intercellular delivery vehicles. Trends Cell Biol 27(3):172–188

    Article  CAS  PubMed  Google Scholar 

  36. He RZ, Luo DX, Mo YY (2019) Emerging roles of lncRNAs in the post-transcriptional regulation in cancer. Genes Dis 6(1):6–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wang W, Wang L, Ruan L et al (2018) Extracellular vesicles extracted from young donor serum attenuate inflammaging via partially rejuvenating aged T-cell immunotolerance. FASEB J 32(11):5899–5912

    Article  CAS  PubMed Central  Google Scholar 

  38. Agarwal U, George A, Bhutani S et al (2017) Experimental, systems, and computational approaches to understanding the MicroRNA-mediated reparative potential of cardiac progenitor cell-derived exosomes from pediatric patients. Circ Res 120(4):701–712

    Article  CAS  PubMed  Google Scholar 

  39. Tan JL, Lau SN, Leaw B et al (2018) Amnion epithelial cell-derived exosomes restrict lung injury and enhance endogenous lung repair. Stem Cells Transl Med 7(2):180–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bruno S, Tapparo M, Collino F et al (2017) Renal regenerative potential of different extracellular vesicle populations derived from bone marrow mesenchymal stromal cells. Tissue Eng 23(21–22):1262–1273

    Article  CAS  Google Scholar 

  41. Patel NA, Moss LD, Lee JY et al (2018) Long noncoding RNA MALAT1 in exosomes drives regenerative function and modulates inflammation-linked networks following traumatic brain injury. J Neuroinflammation 15(1):204

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Arvidson K, Abdallah BM, Applegate LA et al (2011) Bone regeneration and stem cells. J Cell Mol Med 15(4):718–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mori G, D’Amelio P, Faccio R et al (2013) The interplay between the bone and the immune system. Clin Dev Immunol 2013:720504

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Martins M, Ribeiro D, Martins A et al (2016) Extracellular vesicles derived from osteogenically induced human bone marrow mesenchymal stem cells can modulate lineage commitment. Stem Cell Rep 6(3):284–291

    Article  CAS  Google Scholar 

  45. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA et al (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A 107(14):6328–6333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Xu JF, Yang GH, Pan XH et al (2014) Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. PLoS One 9(12):e114627

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Wei J, Li H, Wang S, Li T et al (2014) Let-7 enhances osteogenesis and bone formation while repressing adipogenesis of human stromal/mesenchymal stem cells by regulating HMGA2. Stem Cells Dev 23(13):1452–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhang J, Liu X, Li H et al (2016) Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway. Stem Cell Res Ther 7(1):136

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Otsuru S, Desbourdes L, Guess AJ et al (2018) Extracellular vesicles released from mesenchymal stromal cells stimulate bone growth in osteogenesis imperfecta. Cytotherapy 20(1):62–73

    Article  CAS  PubMed  Google Scholar 

  50. Qin Y, Wang L, Gao Z et al (2016) Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Sci Rep 6:21961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Furuta T, Miyaki S, Ishitobi H et al (2016) Mesenchymal stem cell-derived exosomes promote fracture healing in a mouse model. Stem Cells Transl Med 5(12):1620–1630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wei Y, Tang C, Zhang J et al (2019) Extracellular vesicles derived from the mid-to-late stage of osteoblast differentiation markedly enhance osteogenesis in vitro and in vivo. Biochem Biophys Res Commun 514(1):252–258

    Article  CAS  PubMed  Google Scholar 

  53. Cui Y, Luan J, Li H et al (2016) Exosomes derived from mineralizing osteoblasts promote ST2 cell osteogenic differentiation by alteration of microRNA expression. FEBS Lett 590(1):185–192

    Article  CAS  PubMed  Google Scholar 

  54. Deng L, Wang Y, Peng Y et al (2015) Osteoblast-derived microvesicles: a novel mechanism for communication between osteoblasts and osteoclasts. Bone 79:37–42

    Article  CAS  PubMed  Google Scholar 

  55. Li D, Liu J, Guo B et al (2016) Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun 7:10872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bonewald LF (2002) Osteocytes: a proposed multifunctional bone cell. J Musculoskelet Neuronal Interact 2(3):239–241

    CAS  PubMed  Google Scholar 

  57. Holliday LS, McHugh KP, Zuo J et al (2017) Exosomes: novel regulators of bone remodelling and potential therapeutic agents for orthodontics. Orthod Craniofac Res 20(Suppl 1):95–99

    Article  PubMed  PubMed Central  Google Scholar 

  58. Qin Y, Peng Y, Zhao W et al (2017) Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: a novel mechanism in muscle-bone communication. J Biol Chem 292(26):11021–11033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ponzetti M, Rucci N (2019) Updates on osteoimmunology: What’s new on the cross-talk between bone and immune system. Front Endocrinol (Lausanne) 10:236

    Article  Google Scholar 

  60. Schlundt C, El Khassawna T, Serra A et al (2018) Macrophages in bone fracture healing: their essential role in endochondral ossification. Bone 106:78–89

    Article  CAS  PubMed  Google Scholar 

  61. Wu AC, Raggatt LJ, Alexander KA et al (2013) Unraveling macrophage contributions to bone repair. Bonekey Rep 2:373

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Tsiridis E, Upadhyay N, Giannoudis P (2007) Molecular aspects of fracture healing: which are the important molecules? Injury 38:S11–S25

    Article  PubMed  Google Scholar 

  63. Alexander KA, Chang MK, Maylin ER et al (2011) Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model. J Bone Miner Res 26(7):1517–1532

    Article  CAS  PubMed  Google Scholar 

  64. Wei F, Li M, Crawford R et al (2019) Exosome-integrated titanium oxide nanotubes for targeted bone regeneration. Acta Biomater 86:480–492

    Article  CAS  PubMed  Google Scholar 

  65. Silva AM, Almeida MI, Teixeira JH et al (2017) Dendritic cell-derived extracellular vesicles mediate mesenchymal stem/stromal cell recruitment. Sci Rep 7(1):1667

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Ekstrom K, Omar O, Graneli C et al (2013) Monocyte exosomes stimulate the osteogenic gene expression of mesenchymal stem cells. PLoS One 8(9):e75227

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Zarychta-Wisniewska W, Burdzinska A, Kulesza A et al (2017) Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties. BMC Cell Biol 18(1):13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Kim H, Wang SY, Kwak G et al (2019) Exosome-guided phenotypic switch of M1 to M2 macrophages for cutaneous wound healing. Adv Sci (Weinh) 6(20):1900513

    Article  CAS  Google Scholar 

  69. Pan Y, Hui X, Hoo RLC et al (2019) Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation. J Clin Invest 129(2):834–849

    Article  PubMed  PubMed Central  Google Scholar 

  70. Zhao J, Li X, Hu J, Chen F et al (2019) Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization. Cardiovasc Res 115(7):1205–1216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhao H, Shang Q, Pan Z et al (2018) Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue. Diabetes 67(2):235–247

    Article  CAS  PubMed  Google Scholar 

  72. Guilloton F, Caron G, Menard C et al (2012) Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes. Blood 119(11):2556–2567

    Article  CAS  PubMed  Google Scholar 

  73. Zhou Y, Huang R, Fan W et al (2018) Mesenchymal stromal cells regulate the cell mobility and the immune response during osteogenesis through secretion of vascular endothelial growth factor a. J Tissue Eng Regen Med 12(1):e566–ee78

    Article  CAS  PubMed  Google Scholar 

  74. Wang X, Gu H, Qin D et al (2015) Exosomal miR-223 contributes to mesenchymal stem cell-elicited cardioprotection in polymicrobial sepsis. Sci Rep 5:13721

    Article  PubMed  PubMed Central  Google Scholar 

  75. Sun W, Zhao C, Li Y et al (2016) Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity. Cell Discov 2:16015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ramachandran A, Ravindran S, Huang CC et al (2016) TGF beta receptor II interacting protein-1, an intracellular protein has an extracellular role as a modulator of matrix mineralization. Sci Rep 6:37885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Qi X, Zhang J, Yuan H et al (2016) Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats. Int J Biol Sci 12(7):836–849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Li W, Liu Y, Zhang P et al (2018) Tissue-engineered bone immobilized with human adipose stem cells-derived exosomes promotes bone regeneration. ACS Appl Mater Interfaces 10(6):5240–5254

    Article  CAS  PubMed  Google Scholar 

  79. Derby B (2012) Printing and prototyping of tissues and scaffolds. Science 338(6109):921–926

    Article  CAS  PubMed  Google Scholar 

  80. Xie H, Wang Z, Zhang L et al (2016) Development of an angiogenesis-promoting microvesicle-alginate-polycaprolactone composite graft for bone tissue engineering applications. Peer J 4:e2040

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Diomede F, Gugliandolo A, Cardelli P et al (2018) Three-dimensional printed PLA scaffold and human gingival stem cell-derived extracellular vesicles: a new tool for bone defect repair. Stem Cell Res Ther 9(1):104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Xie H, Wang Z, Zhang L et al (2017) Extracellular vesicle-functionalized decalcified bone matrix scaffolds with enhanced pro-angiogenic and pro-bone regeneration activities. Sci Rep 7:45622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Fu Y, Mo A (2018) A review on the electrochemically self-organized titania nanotube arrays: synthesis, modifications, and biomedical applications. Nanoscale Res Lett 13(1):187

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Yang Y, Li X, Qiu H et al (2018) Polydopamine modified TiO2 nanotube arrays for long-term controlled elution of bivalirudin and improved hemocompatibility. ACS Appl Mater Interfaces 10(9):7649–7660

    Article  CAS  PubMed  Google Scholar 

  85. Szatanek R, Baran J, Siedlar M et al (2015) Isolation of extracellular vesicles: determining the correct approach (Review). Int J Mol Med 36(1):11–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yamashita T, Takahashi Y, Takakura Y (2018) Possibility of exosome-based therapeutics and challenges in production of exosomes eligible for therapeutic application. Biol Pharm Bull 41(6):835–842

    Article  CAS  PubMed  Google Scholar 

  87. Lv LL, Wu WJ, Feng Y et al (2018) Therapeutic application of extracellular vesicles in kidney disease: promises and challenges. J Cell Mol Med 22(2):728–737

    PubMed  Google Scholar 

  88. Willis GR, Kourembanas S, Mitsialis SA (2017) Toward exosome-based therapeutics: isolation, heterogeneity, and fit-for-purpose potency. Front Cardiovasc Med 4:63

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Watson DC, Bayik D, Srivatsan A et al (2016) Efficient production and enhanced tumor delivery of engineered extracellular vesicles. Biomaterials 105:195–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Health and Medical Research Council (NHMRC) Early Career Fellowship (Grant No. 1105035), the National Natural Science Foundation of China (NSFC) General Project (Grant No. 31771025), and the NSFC Young Scientists Fund (Grant No. 81700969).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yinghong Zhou .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Zhou, Y., Xiao, Y. (2020). The Development of Extracellular Vesicle-Integrated Biomaterials for Bone Regeneration. In: Chun, H., Reis, R., Motta, A., Khang, G. (eds) Biomimicked Biomaterials. Advances in Experimental Medicine and Biology, vol 1250. Springer, Singapore. https://doi.org/10.1007/978-981-15-3262-7_7

Download citation

Publish with us

Policies and ethics