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Stem Cell-Based Tissue Engineering for Bone Repair

Influence of Cell Communication and 3-D Cell-Matrix Environment

  • Chapter
Tissue Engineering

Part of the book series: Computational Methods in Applied Sciences ((COMPUTMETHODS,volume 31))

Abstract

Culturing cells in 3D scaffolds can help model a physiological process. The property of the substrate used for such scaffolds has been shown to modify and determine stem cell lineage. Using this knowledge, in-vitro 3D stem cell culture models with ex-vivo bone tissue investigations can offer insight and inspiration for the development of novel therapies for bone defects. Although many different scaffolds have been created for bone tissue repair, in situ cell level mechanics are not always given consideration as the main design target. Overall, the ideal tissue engineering solution to bone regeneration would incorporate cells of osteogenic potential into a synthetic bone scaffold in order to reduce the need for external factors added such as drugs or growth factors. Attention to the mechanical aspects of the bone to be studied as well as the cells to be placed within the scaffold is fundamental. In this chapter, we will explore studies investigating the role of cell communication in bone mechanosensing, including the roles of different bone cells in the process of bone adaptation and repair, and the use of this knowledge in creating a novel tissue engineering strategy for the repair of acute bone defects.

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References

  1. Marks SC, Popoff SN (1988) Bone cell biology: the regulation of development, structure, and function in the skeleton. Am J Anat 183:1–44

    Article  Google Scholar 

  2. Willie BM, Petersen A, Schmidt-Bleek K et al. (2010) Designing biomimetic scaffolds for bone regeneration: why aim for a copy of mature tissue properties if nature uses a different approach? Soft Matter 6:4976–4987

    Article  Google Scholar 

  3. McKibbin B (1978) The biology of fracture healing in long bones. J Bone Jt Surg 60-B(2):150–162

    Google Scholar 

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

    Article  Google Scholar 

  5. Marsh D (1998) Concepts of fracture union, delayed union, and nonunion. Clin Orthop Relat Res 355:S22–S30

    Article  Google Scholar 

  6. Anglen J (2002) Enhancement of fracture healing with bone stimulators. Tech Orthop 17(4):506–514

    Article  Google Scholar 

  7. D’Aubigne RM (1949) Surgical treatment of nonunion of long bones. J Bone Jt Surg 31:256–266

    Google Scholar 

  8. AAOS (2007) Nonunions. American Academy of Orthopedic Surgeons, Rosemont. http://orthoinfo.aaos.org/topic.cfm?topic=A00374. Cited 15 Feb 2012

    Google Scholar 

  9. Crockett JC, Rogers MJ, Coxon FP et al. (2011) Bone remodelling at a glance. J Cell Sci 124:991–998

    Article  Google Scholar 

  10. Batra N, Kar R, Jiang J (2011) Gap junctions and hemichannels in signal transmission, function and development of bone. Biochim Biophys Acta. doi:10.1016/j.bbamem.2011.09.018

    Google Scholar 

  11. Jiang JX, Siller-Jackson AJ, Burra S (2007) Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress. Front Biosci 12:1450–1462

    Article  Google Scholar 

  12. Stains JP, Civitelli R (2005) Gap junctions in skeletal development and function. Biochim Biophys Acta 1719:69–81

    Article  Google Scholar 

  13. Ishihara Y, Kamioka H, Honjo T et al. (2008) Hormonal, pH, and calcium regulation of connexin 43-mediated dye transfer in osteocytes in chick calvaria. J Bone Miner Res 23(3):350–360

    Article  Google Scholar 

  14. Matemba SF, Lie A, Ransjo M (2006) Regulation of osteoclastogenesis by gap junction communication. J Cell Biochem 99(2):528–537

    Article  Google Scholar 

  15. Watkins M, Grimston SK, Norris JY et al. (2011) Osteoblast connexin 43 modulates skeletal architecture by regulating both arms of bone remodelling. Mol Biol Cell 22:1240–1251

    Article  Google Scholar 

  16. Su M, Borke JL, Donahue HJ et al. (1997) Expression of connexin 43 in rat mandibular bone and periodontal ligament cells during experimental tooth movement. J Dent Res 76:1357–1366

    Article  Google Scholar 

  17. Cheng B, Zhao S, Luo J et al. (2001) Expression of functional gap junctions and regulation by fluid flow shear stress in osteocyte-like MLO-Y4 cells. J Bone Miner Res 16:249–259

    Article  Google Scholar 

  18. Civitelli R (2008) Cell-cell communication in the osteoblast/osteocyte lineage. Biochem Biophys 473:188–192

    Article  Google Scholar 

  19. Genetos DC, Geist DJ, Liu D et al. (2005) Fluid shear-induced ATP secretion mediates prostaglandin release in MC3T3-E1 osteoblasts. J Bone Miner Res 20:41–49

    Article  Google Scholar 

  20. Dale B, Gualtieri R, Talevi R et al. (1991) Intercellular communication in the early human embryo. Mol Reprod Dev 29(1):21–28

    Article  Google Scholar 

  21. Mbalaviele G, Shin CS, Civitelli R (2006) Cell-cell adhesion and signaling through cadherins: connecting bone cells in their microenvironment. J Bone Miner Res 21(12):1821–1827

    Article  Google Scholar 

  22. Schwartz MA, DeSimone DW (2008) Cell adhesion receptors in mechanotransduction. Curr Opin Cell Biol 20:551–556

    Article  Google Scholar 

  23. Pokutta S, Weis WI (2007) Structure and mechanism of cadherins and catenins in cell-cell contacts. Annu Rev Cell Dev Biol 23:237–261

    Article  Google Scholar 

  24. Ganz A, Lambert M, Saez A et al. (2006) Traction forces exerted through N-cadherin contacts. Biol Cell 98:721–730

    Article  Google Scholar 

  25. Leucht P, Kim JB, Currey JA et al. (2007) FAK-mediated mechanotransduction in skeletal regeneration. PLoS ONE 2:e390

    Article  Google Scholar 

  26. Rhee ST, El-Bassiony L, Buchman SR (2006) Extracellular signal-related kinase and bone morphogenetic protein expression during distraction osteogenesis of the mandible: in vivo evidence of a mechanotransduction mechanism for differentiation and osteogenesis by mesenchymal precursor cells. Plast Reconstr Surg 117:2243–2249

    Article  Google Scholar 

  27. Duong LT, Lakkakorpi P, Nakamura I et al. (2000) Integrins and signaling in osteoclast function. Matrix Biology 19:97–105

    Article  Google Scholar 

  28. Houghton FD (2005) Role of gap junctions during early embryo development. Reproduction 129(2):129–135

    Article  Google Scholar 

  29. Nakamura I, Duong LT, Rodan SB et al. (2007) Involvement of alpha-v-beta-3 integrins in osteoclast function. J Bone Miner Metab 25:337–344

    Article  Google Scholar 

  30. Pioletti DP (2010) Biomechanics in bone tissue engineering. Comput Methods Biomech Biomed Eng 13(6):837–846

    Article  Google Scholar 

  31. Juncosa N, West JR, Galloway MT et al. (2003) In vivo forces used to develop design parameters for tissue engineered implants for rabbit patellar tendon repair. J Biomech 36:483–488

    Article  Google Scholar 

  32. Tate ML, Knothe U (2000) An ex vivo model to study transport processes and fluid flow in loaded bone. J Biomech 33:247–254

    Article  Google Scholar 

  33. Blecha LD, Rakotomanana L, Razafimahery F et al. (2009) Targeted mechanical properties for optimal fluid motion inside artificial bone substitutes. J Orthop Res 27:1082–1089

    Article  Google Scholar 

  34. Behravesh E, Yasko AW, Engel PS et al. (1999) Synthetic biodegradable polymers for orthopaedic applications. Clin Orthop 367S:118–129

    Article  Google Scholar 

  35. Stevens MM, Marini RP, Schaefer D et al. (2005) In vivo engineering of organs: the bone bioreactor. Proc Natl Acad Sci USA 102:11450–11455

    Article  Google Scholar 

  36. Li F, Li S, Ghzaoui AE et al. (2007) Synthesis and gelation properties of PEG-PLA-PEG triblock copolymers obtained by coupling monohydroxylated PEG-PLA with adipoyl chloride. Langmuir 27:2778–2783

    Article  Google Scholar 

  37. Ryner M, Albertsson AC (2002) Resorbable and highly elastic block copolymers from 1,5-dioxepan-2-one and L-lactide with controlled tensile properties and hydrophilicity. Biomacromolecules 3:601–608

    Article  Google Scholar 

  38. Ryner M, Valdre A, Albertsson AC (2002) Star-shaped and photo-crosslinked poly(1,5-dioxepan-2-one)—synthesis and characterization. J Polym Sci, Part A, Polym Sci 40:2049–2054

    Article  Google Scholar 

  39. Iqbal M, Xu X (2009) A review on biodegradable polymeric materials for bone tissue. J Mater Sci 44(51):5713–5724

    Google Scholar 

  40. Swaminathan V, Tchao R, Jonnalaggada S (2007) Physical characterization of thin semi-porous poly(L-lactic acid)/poly(ethylene glycol) membranes for tissue engineering. J Biomater Sci Polym Ed 18(10):1321–1333

    Article  Google Scholar 

  41. Kroeze RJ, Helder MN, Govaert LE et al. (2009) Biodegradable polymers in bone tissue engineering. Materials 2:833–856

    Article  Google Scholar 

  42. Cai ZY, Yang DA, Zhang N et al. (2009) Poly(propylene-fumarate)/(calcium sulfate/β-tricalcium phosphate) composites: preparation, characterization and in-vitro degradation. Acta Biomater 5:628–635

    Article  Google Scholar 

  43. Pelin IM, Maier SS, Chitanu GC et al. (2009) Preparation and characterization of a hydroxyapatite-collagen composite as component for injectable bone substitute. Mater Sci Eng 29:2188–2194

    Article  Google Scholar 

  44. Hollister SJ (2005) Porous scaffold design for tissue engineering. Nat Mater 4:518–524

    Article  Google Scholar 

  45. Alessandri G, Emanueli C, Madeddu P (2004) Genetically engineered stem cell therapy for tissue regeneration. Ann NY Acad Sci 1015:271–284

    Article  Google Scholar 

  46. Rahaman MN, Mao JJ (2005) Stem cell-based composite tissue constructs for regenerative medicine. Biotechnol Bioeng 91:261–284

    Article  Google Scholar 

  47. Lee DA, Knight MM, Campbell JJ et al. (2011) Stem cell mechanobiology. J Cell Biochem 112:1–9

    Article  Google Scholar 

  48. Guilak F, Cohen DM, Estes BT et al. (2009) Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell 5:17–26

    Article  Google Scholar 

  49. Battista S, Guarnieri D, Borselli C et al. (2005) The effect of matrix composition of 3D constructs on embryonic stem cell differentiation. Biomaterials 26:6194–6207.

    Article  Google Scholar 

  50. Weyts FA, Bosmans B, Niesing R et al. (2003) Mechanical control of human osteoblast apoptosis and proliferation in relation to differentiation. Calcif Tissue Int 4:505–512

    Article  Google Scholar 

  51. Thompson MS, Epari DR, Bieler F et al. (2010) In vitro models for bone mechanobiology: applications in bone regeneration and tissue engineering. Proc Inst Mech Eng 224:1533–1541

    Article  Google Scholar 

  52. Epari DR, Duda GN, Thompson MS (2010) Mechanobiology of bone healing and regeneration: in vivo models. Proc Inst Mech Eng 224:1543–1553

    Article  Google Scholar 

  53. Ziambaras K, Lecanda F, Steinberg TH et al. (1998) Cyclic stretch enhances gap junctional communication between osteoblastic cells. J Bone Miner Res 13(2):218–228

    Article  Google Scholar 

  54. Grimston SK, Screen J, Haskell JH et al. (2006) Role of connexin 43 in osteoblast response to physical load. Ann NY Acad Sci 1068:214–224

    Article  Google Scholar 

  55. Zhang L, Wang P, Mei S et al. (2011) In vivo alveolar bone regeneration by bone marrow stem cells/fibrin glue composition. Oral Biology. doi:10.1016/j.archoralbio.2011.08.025

    Google Scholar 

  56. Kim H, Park J, Lee JK et al. (2008) Transplanted xenogenic bone marrow stem cells survive and generate new bone formation in the posterolateral lumbar spine of non-immunosuppressed rabbits. Eur Spine J 17:1515–1521

    Article  Google Scholar 

  57. Minamide A, Yoshida M, Kawakami M et al. (2005) The use of cultured bone marrow cells in type I collagen gel and porous hydroxyapatite for posterolateral lumbar spine fusion. Spine 30(10):1134–1138

    Article  Google Scholar 

  58. Grimston SK, Brodt MD, Silva MJ et al. (2008) Attenuated response to in vivo mechanical loading in mice with conditional osteoblast ablation of the connexin 43 gene (GJA1). J Bone Miner Res 23(6):879–886

    Article  Google Scholar 

  59. Goodship AE, Kenwright J (1985) The influence of induced micromovement upon the healing of experimental tibial fractures. J Bone Jt Surg 67(4):650–655

    Google Scholar 

  60. Kenwright J, Goodship AE (1989) Controlled mechanical stimulation in the treatment of tibial fractures. Clin Orthop Relat Res 241:36–47

    Google Scholar 

  61. Rubin C, Judex S, Qin YX (2006) Low-level mechanical signals and their potential as a non-pharmacological intervention for osteoporosis. Age Ageing 35(S2):32–36

    Google Scholar 

  62. Augat P, Merk J, Wolf S et al. (2001) Mechanical stimulation by external application of cyclic tensile strains does not effectively enhance bone healing. J Orthop Trauma 15(1):54–60

    Article  Google Scholar 

  63. Hente R, Fuchtmeier B, Schlegel U et al. (2004) The influence of cyclic compression and distraction on the healing of experimental tibial fractures. J Orthop Res 22(4):709–715

    Article  Google Scholar 

  64. Wang X, Nyman JS, Dong X et al. (2010) Fundamental biomechanics in bone tissue engineering. doi:10.2200/S00246ED1V01Y200912TIS004

    Google Scholar 

  65. Krawetz R, Cormier J, Wu Y et al. (2011) Collagen I scaffolds cross-linked with beta-glycerol phosphate induce osteogenic differentiation of embryonic stem cells in vitro and regulates their tumorigenic potential in vivo. Tissue Eng, Part A. doi:10.1089/ten.TEA.2011.0174

    Google Scholar 

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Author information

Authors and Affiliations

  1. McCaig Institute for Bone and Joint Health, Faculty of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada

    Swathi Damaraju

  2. Departments of Civil Engineering and Surgery, Schulich School of Engineering, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada

    Neil A. Duncan

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  1. Swathi Damaraju
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  2. Neil A. Duncan
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Correspondence to Swathi Damaraju .

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Editors and Affiliations

  1. Instituto Superior Tecnico Mechanical Engineering Dept., Technical University of Lisbon, Grande Lisboa, Portugal

    Paulo Rui Fernandes

  2. CDRSP – IP Leiria Portugal, Marinha Grande, Portugal

    Paulo Jorge Bartolo

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Damaraju, S., Duncan, N.A. (2014). Stem Cell-Based Tissue Engineering for Bone Repair. In: Fernandes, P., Bartolo, P. (eds) Tissue Engineering. Computational Methods in Applied Sciences, vol 31. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7073-7_1

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  • DOI: https://doi.org/10.1007/978-94-007-7073-7_1

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-7072-0

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