Skip to main content
SpringerLink
Log in

The Role of Polymer Additives in Enhancing the Response of Calcium Phosphate Cement

  • Chapter
  • First Online:
Orthopedic Biomaterials

Abstract

Bone defects caused by trauma, tumors, errors in development, disease, and fractures occur within young and aging populations. Dysfunction, impairment, and pain are the main reasons that patients seek clinical intervention each year. In many of these cases, revision procedures are needed due to subsequent bone infection and resorption, bone mass loss, reemergence of bone cancer reoccurrence or failure of new bone tissue to grow. Revision procedures and increased hospital stays can cost hundreds of thousands of dollars for a single patient, significant lost time from work, altered and restricted lifestyles, and in some cases, death. Additionally, high-risk individuals in the population have led to an increase in the need for additional surgical operations due to device or implant failure or infection. The dental and orthopedic device industry also face major consumer demands for more functional, bioinstructional, and longer-lasting implants. A significant body of research has been directed towards addressing these concerns by examining the use of polymer additives that enhance calcium phosphate cement properties through the addition of enhanced functionalities.

The number of papers, application and review papers, published on calcium phosphate cement is staggering as is the use of additives. This chapter’s mission is to provide a review of the most relevant developments in this field. The chapter’s focus is on the application of natural and synthetic polymers designed to enhance calcium phosphate cement (CPC) by enhancing CPC’s inherent properties and providing additional functionalities.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
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. Liu Y, Lim, Teoh S-H. Review: development of clinically relevant scaffolds for vascularised bone tissue engineering. Biotechnol Adv. 2013;31:688–705.

    Article  PubMed  CAS  Google Scholar 

  2. Cortesini R. Stem cells, tissue engineering and organogenesis in transplantation. Transpl Immunol. 2005;15:81–9.

    Article  PubMed  CAS  Google Scholar 

  3. Amini AR, Laurencin CT, Nukavarapu SP. Bone tissue engineering: recent advances and challenges. Crit Rev Bioeng. 2012;40:363–408.

    Google Scholar 

  4. Cancedda R, Dozin B, Giannoni P, Quarto R. Tissue engineering and cell therapy of cartilage and bone. Matrix Biol. 2003;22:81–91.

    Article  PubMed  CAS  Google Scholar 

  5. Oryan A, Alidadi S, Moshiri A, Maffuli N. Bone regenerative medicine: classic options, novel strategies, and future directions. J. Orthop Surg Res. 2014;9(18):1–17.

    Google Scholar 

  6. Stevens MM. Biomaterials for bone tissue engineering. Mater Today. 2008;11(5):18–25.

    Article  CAS  Google Scholar 

  7. Katagiri BT, Takahashi N. Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis. 2002;8:147–59.

    Article  PubMed  CAS  Google Scholar 

  8. Rose FR, Hou Q, Oreffo RO. Delivery systems for bone growth factors - the new players in skeletal regeneration. J Pharm Pharmacol. 2004;56:415–27.

    Article  PubMed  CAS  Google Scholar 

  9. Matassi F, et al. New biomaterials for bone regeneration. Clin Cases Min Bone Metab. 2011;8:21–4.

    Google Scholar 

  10. Khashaba RM, Moussa MM, Mettenburg DJ, Rueggeberg FA, Chutkan NB, Borke JL. Polymeric-calcium phosphate cement composites-material properties: in vitro and in vivo investigations. Int J Biomater. 2010; 2010: 691452, 14 pages.

    Google Scholar 

  11. Puppi D, Chiellini F, Piras AM, Chiellini E. Polymeric materials for bone and cartilage repair. Prog Poly Sci. 2010;35:403–40.

    Article  CAS  Google Scholar 

  12. Griffin MF, Kalaskar DM, Seifalian A, Butler PE. An update on the application of nanotechnology in bone tissue engineering. Open Orthop J. 2016;10(Suppl-3, M4):836–48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Rosa N, Simoes R, Magalhães FD, Marques AT. From mechanical stimulus to bone formation: a review. Med Eng Phys. 2015;37(8):719–28. https://doi.org/10.1016/j.medengphy.2015.05.015.

    Article  PubMed  Google Scholar 

  14. Ginebra MP. Cements as bone repair materials. In: Planell JA, editor. Bone repair biomaterials. Cambridge, England: Woodhead Publishing Limited; 2009.

    Google Scholar 

  15. Hollinger J, Einhorn TA, Doll F, Sfeir C. Bone tissue engineering. Boca Raton, FL: CRC Press; 2004.

    Google Scholar 

  16. Pilliar RM, Filiaggi M, Wells JD, Grynpas MD, Kandel RA. Porous calcium polyphosphate scaffolds for bone substitute applications in vitro characterization. Biomaterials. 2001;22:963–72.

    Article  PubMed  CAS  Google Scholar 

  17. Foppiano S, Marshall SJ, Marshall GW, Saiz E, Tomsia AP. The influence of novel bioactive glasses on in vitro osteoblast behavior. J Biomed Mater Res. 2004;71A:242–9.

    Article  CAS  Google Scholar 

  18. Wang L, Singh M, Bonewald LF, Detamore MS. Signaling strategies for osteogenic differentiation of human umbilical cord mesenchymal stromal cells for 3D bone tissue engineering. J Tiss Eng Regen Med. 2009;3:398–404.

    Article  CAS  Google Scholar 

  19. Dorozhkin SV, Epple M. Biological and medical significance of calcium phosphates. Angew Chem Int Ed. 2002;41:3130–46.

    Article  CAS  Google Scholar 

  20. Barinov S, Komlev VS. Calcium phosphate bone cements. Inorg Mater. 2011;47(13):1470–85.

    Article  CAS  Google Scholar 

  21. Bouler JM, Pilet P, Gauthier O, Verron E. Biphasic calcium phosphate ceramics for bone reconstruction: areview of biological response. Acta Biomater. 2017;53:1–12.

    Article  PubMed  CAS  Google Scholar 

  22. Dorozhkin SV. Calcium orthophosphates. J Mater Sci Mater Med. 2007;42(4):1061–95.

    Article  CAS  Google Scholar 

  23. LeGeros RZ, Chohayeb A, Shulman A. Apatitic calcium phosphates: possible dental restorative materials. J Dent Res. 1982;61:343.

    Google Scholar 

  24. Link DP, van den Dolder J, van den Beucken JJ, Wolke JG, Mikos AG, Jansen JA. Bone response and mechanical strength of rabbit femoral defects filled with injectable CaP cements containing TGF-b1 loaded gelatin microspheres. Biomaterials. 2008;29:675–82.

    Article  PubMed  CAS  Google Scholar 

  25. Zhao L, Weir MD, Xu HHK. Human umbilical cord stem cell encapsulation in calcium phosphate scaffolds for bone engineering. Biomaterials. 2010;31:3848–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Ducheyne P, Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials. 1999;20:2287–303.

    Article  PubMed  CAS  Google Scholar 

  27. Bohner M. Reactivity of calcium phosphate cements. J Mater Chem. 2007;17(38):3980–92.

    Article  CAS  Google Scholar 

  28. Friedman CD, Costantino PD, Takagi S, Chow LC. BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction. J Biomed Mater Res. 1998;43:428–32.

    Article  PubMed  CAS  Google Scholar 

  29. Kühn KD. Properties of bone cement. In: Breusch S, editor. The well-cemented total hip arthroplasty. Heidelberg: Springer MedizinVerlag; 2005. p. 52–9.

    Chapter  Google Scholar 

  30. Ginebra MP, Traykova T, Planell JA. Calcium phosphate cements: competitive drug carriers for the musculoskeletal system? Biomaterials. 2006;27:2171–7.

    Article  PubMed  CAS  Google Scholar 

  31. O'Dowd-Booth CJ, White J, Smitham P, Khan W, Marsh DR. Bone cement: perioperative issues, orthopaedic applications and future developments. J Perioper Pract. 2011;21(9):304–8.

    Article  PubMed  Google Scholar 

  32. Constantz BR, Ison IC, Fulmer MT, Poser RD, Smith ST, Van Wagoner M, et al. Skeletal repair by in situ formation of the mineral phase of bone. Science. 1995;267:1796–9.

    Article  PubMed  CAS  Google Scholar 

  33. DiMaio FR. The science of bone cement: a historical review. Orthopedics. 2002;25(12):1399–407.

    PubMed  Google Scholar 

  34. Komlev VS, Fadeeva IV, Gurin N, Shvorneva LI, Bakunova NV, Barino SM. New calcium phosphate cements based on tricalcium phosphate. Dokl Chem. 2011;437(1):75–8.

    Article  CAS  Google Scholar 

  35. Eliaz N, Metok N. Calcium phosphate bioceramics: a review of their history, structure, properties, coating technologies and biomedical applications. Materials. 2017;10(4):334. https://doi.org/10.3390/ma10040334.

    Article  PubMed Central  CAS  Google Scholar 

  36. Perez RA, Kim HW, Ginebra MP. Polymeric additives to enhance the functional properties of calcium phosphate cements. J Tiss Eng. 2012;3(1):2041731412439555. https://doi.org/10.1177/2041731412439555. published online 20 March.

    Article  CAS  Google Scholar 

  37. Maestretti G, Cremer C, Otten P, Jakob RP. Prospective study of standalone balloon kyphoplasty with calcium phosphate cement augmentation in traumatic fractures. Eur Spine J. 2007;16:601–10.

    Article  PubMed  Google Scholar 

  38. Aral A, Yalçin S, Karabuda ZC, Anil A, Jansen JA, Mutlu Z. Injectable calcium phosphate cement as a graft material for maxillary sinus augmentation: an experimental pilot study. Clin Oral Implants Res. 2008;19:612–7.

    Article  PubMed  Google Scholar 

  39. Kroeses-Deitman HC, Wolke JG, Spauwen PH, Jansen JA. Closing capacity of cranial bone defects using porous calcium phosphate cement implants in a rabbit animal model. J Biomed Mater Res A. 2006;79:503–11.

    Article  CAS  Google Scholar 

  40. Libicher M, Hillmeier J, Liegibel U, Sommer U, Pyerin W, Vetter M. Osseous integration of calcium phosphate in osteoporotic vertebral fractures after kyphoplasty: initial results from a clinical and experimental pilot study. Osteoporos Int. 2006;17:1208–15.

    Article  PubMed  CAS  Google Scholar 

  41. Mermelstein LE, Chow LC, Friedman CD, Crisco JJ. The reinforcement of cancellous bone screws with calcium phosphate cement. J Orthop Trauma. 1996;10:15–20.

    Article  PubMed  CAS  Google Scholar 

  42. Ooms E, Wolke J, Van der Waerden J, Jansen J. Use of injectable calcium-phosphate cement for the fixation of titanium implants: an experimental study in goats. J Biomed Mater Res B Appl Biomater. 2003;66:447–56.

    Article  PubMed  CAS  Google Scholar 

  43. Takemasa R, Kiyasu K, Tani T, Inoue S. Validity of calcium phosphate cement vertebroplasty for vertebral non-union after osteoporotic fracture with middle column involvement. Spine J. 2007;7:148S.

    Article  Google Scholar 

  44. Lewis G. Injectable bone cements for use in vertebroplasty and kyphoplasty: state-of-the-art review. J Biomed Mater Res B Appl Biomat. 2006;76:456–68.

    Article  CAS  Google Scholar 

  45. Calcium phosphate: structure, synthesis, properties, and applications. In: Robert B, editor. Heimann: Biochemistry Research Trends; 2012. 498pp. ISBN: 978-1-62257-299-1.

    Google Scholar 

  46. Habraken H, Habibovic P, Epple M, Bohner M. Calcium phosphates in biomedical applications: materials for the future? Mat Today. 2016;19(2):69–87.

    Article  CAS  Google Scholar 

  47. Barinov SM. Trends in development of calcium phosphate-based ceramic and composite materials for medical applications: transition to nanoscale. Russian J Gen Chem. 2010;80:666–74.

    Article  CAS  Google Scholar 

  48. Dutta PK. Chitin and chitosan for regenerative medicine. In: Springer series on polymer and composite materials. Berlin: Springer; 2015.

    Google Scholar 

  49. Zhang JT, Tancret F, Bouler JM. Fabrication and mechanical properties of calcium phosphate cements (CPC) for bone substitution. Mater Sci Eng. 2011;31(4):740–7.

    Article  CAS  Google Scholar 

  50. Driessens FCM, Planell J, Boltong MG, Khairoun I, Ginebra MP. Osteotransductive bone cements. J Eng Med. 1998;212(6):427–35.

    Article  CAS  Google Scholar 

  51. Bigi A, Bracci B, Panzavolta S. Effect of added gelatin on the properties of calcium phosphate cement. Biomaterials. 2004;25(14):2893–9.

    Article  PubMed  CAS  Google Scholar 

  52. Rinaudo M. Chitin and chitosan: properties and applications. Prog Poly Sci. 2006;31(7):603–32.

    Article  CAS  Google Scholar 

  53. Shi C, Zhu Y, Ran X, Wang M, Su Y, Cheng T. Therapeutic potential of chitosan and its derivatives in regenerative medicine. J Surg Res. 2006;133(2):185–92.

    Article  PubMed  CAS  Google Scholar 

  54. Padois K, Rodriguez F. Effects of chitosan addition to self-setting bone cement. Biomed Mater Eng. 2007;17(5):309–20.

    PubMed  CAS  Google Scholar 

  55. Sun L, Hockin H, Xu K, Takagi S, Chow LC. Fast setting calcium phosphate cement–chitosan composite: mechanical properties. J Biomat Appl. 2007;21(3):299–315. https://doi.org/10.1177/0885328206063687.

    Article  CAS  Google Scholar 

  56. Chesnutt BM, Viano AM, Yuan Y, Yang Y, Guda T, Appleford MR, Ong JL, Haggard WO, Bumgardner JD. Design and characterization of a novel chitosan/nanocrystalline calcium phosphate composite scaffold for bone regeneration. J Biomed Mater Res A. 2009;88(2):491–502.

    Article  PubMed  CAS  Google Scholar 

  57. Al-Bayaty FH, Kamaruddin AA, Ismail MA, Abdulla MA. Formulation and evaluation of a new biodegradable periodontal chip containing thymoquinone in a chitosan base for the management of chronic periodontitis. J Nanomat. 2013;2013:397308., 5 pages. https://doi.org/10.1155/2013/397308.

    Article  CAS  Google Scholar 

  58. Janmey PA, Winer JP, Weisel JW. Fibrin gels and their clinical and bioengineering applications. J R Soc Interface. 2009;6(30):1–10.

    Article  PubMed  CAS  Google Scholar 

  59. Balakrishnan B, Mohanty M, Umashanker PR, Jayakrishnan A. Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials. 2005;26:6335–42.

    Article  PubMed  CAS  Google Scholar 

  60. Cui G, Li J, Lei W, et al. The mechanical and biological properties of an injectable calcium phosphate cement-fibrin glue composite for bone regeneration. J Biomed Mater Res B. 2010;92(2):377–85.

    Google Scholar 

  61. Lopez-Heredia MA, Pattipeilohy J, Hsu S, van der Wieden B, Leewenburg SC, et al. Bulk physicochemical, interconnectivity, and mechanical properties of calcium phosphate cements-fibrin glue composites for bone substitute applications. J Biomed Mat Res A. 2013;101(2):478–90.

    Article  CAS  Google Scholar 

  62. Kneser U, Voogd A, Ohnolz J, et al. Fibrin gel-immobilized primary osteoblasts in calcium phosphate bone cement: in vivo evaluation with regard to application as injectable biological bone substitute. Cells Tissues Organs. 2005;179(4):158–69.

    Article  PubMed  CAS  Google Scholar 

  63. Dong J, Cui G, Bi L, Lei W. The mechanical and biological studies of calcium phosphate cement-fibrin glue for bone reconstruction of rabbit femoral defects. Int J Med. 2013;8:1317–24. https://doi.org/10.2147/IJN.S42862.

    Article  CAS  Google Scholar 

  64. Lee L-T, Kwan P-C, Chen Y-F, Wong Y-K. Comparison of the effectiveness of autologous fibrin glue and macroporous biphasic calcium phosphate as carriers in the osteogenesis process with or without mesenchymal stem cells. J Chin Med Assoc. 2008;1(2):66–73.

    Article  Google Scholar 

  65. Gholipour H, Meimandi-Parizi A, Oryan A, Bigham SA. The effects of gelatin, fibrin-platelet glue and their combination on healing of the experimental critical bone defect in a rat model: radiological, histological, scanning ultrastructural and biomechanical evaluation. Cell Tiss Bank. 2017:1–16. Epub 2017 Dec 20.

    Google Scholar 

  66. Meimandi-Parizi A, Oryan A, Gholipour H. Healing potential of nanohydroxyapatite, gelatin, and fibrin-platelet glue combination as tissue engineered scaffolds in radial bone defects of rats. Conn Tiss Res. 2017;16:1–13.

    Google Scholar 

  67. Noori A, Ashrafi S, Vaez-Ghaemi R, Hatamian-Zaremi A, Webster TJ. A review of fibrin and fibrin composites for bone tissue engineering. Intern J Nanomed. 2017;12:4937–61. https://doi.org/10.2147/IJN.S12467183.

    Article  Google Scholar 

  68. Gorgieva S, Kokol V. Collagen vs. gelatine-based biomaterials and their biocompatibility: review and perspectives, biomaterials applications for nanomedicine. In: Pignatello R, editor; 2011. ISBN: 978-953-307-661-4.

    Google Scholar 

  69. Unuma H, Matsuchima Y. Preparation of calcium phosphate cement with an improved setting behavior. J Asian Ceramic Soc. 2013;1(1):26–9.

    Article  Google Scholar 

  70. Azami M, Mohamma RE, Fathollah M. Gelatin/hydroxyapatite nanocomposite scaffolds for bone repair. Plast Res. 2010. doi: https://doi.org/10.1002/spepro.003073.

  71. Kim HW, Knowles JC, Kim HE. Hydroxyapatite and gelatin composite foams processed via novel freeze-drying and crosslinking for use as temporary hard tissue scaffolds. J Biomed Mater Res. 2005;A72:136–45.

    Article  CAS  Google Scholar 

  72. Kim W, Kim HE, Salih V. Stimulation of osteoblast responses to biomimetic nanocomposites of gelatin-hydroxyapatite for tissue engineering scaffolds. Biomaterials. 2005;26:5221–30. https://doi.org/10.1016/j.biomaterials.2005.01.047.

    Article  PubMed  CAS  Google Scholar 

  73. Habraken WJ, Wolke JG, Mikos AG, et al. Porcine gelatin microsphere/calcium phosphate cement composites: an in vitro degradation study. J Biomed Mater Res B. 2009;91(2):555–61.

    Article  CAS  Google Scholar 

  74. Oryan A, Alidadi S, Sadegh B, Mishiri A. Comparative study on the role of gelatin, chitosan and their combination as tissue engineered scaffolds on healing and regeneration of critical sized bone defects: an in vivo study. J Mater Sci Mater Med. 2016;27(10):155–61. https://doi.org/10.1007/s10856-016-5766-6.

    Article  PubMed  CAS  Google Scholar 

  75. Sionkowska A, Skrzyński S, Śmiechowski K, Kołodziejczak A. The review of versatile application of collagen. Polym Adv Technol. 2017;28:4–9. https://doi.org/10.1002/pat.3842.

    Article  CAS  Google Scholar 

  76. Zhang J, Liu W, Schnitzler V, Tancret F, Bouler JM. Calcium phosphate cements for bone substitution: chemistry, handling and mechanical properties. Acta Biomater. 2013;10(3):1035–49.

    Article  PubMed  CAS  Google Scholar 

  77. Dong C, Lv Y. Application of collagen scaffold in tissue engineering: recent advances and new perspectives. Polymers. 2016;8(2):42. https://doi.org/10.3390/polym8020042.

    Article  CAS  PubMed Central  Google Scholar 

  78. Ferreira AM, Gentile P, Chono V, Ciardelli G. Collagen for bone tissue regeneration. Acta Biomat. 2012;8(9):3191–200.

    Article  CAS  Google Scholar 

  79. Wang P, Zhao L, Liu J, Weir MD, Zhou X, Xu H. Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells. Bone Res. 2014;2:14017. https://doi.org/10.1038/boneres.2014.17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Perez RA, Altankov G, Jorge-Herrero E, Ginebra MP. Micro- and nanostructured hydroxyapatite–collagen microcarriers for bone tissue-engineering applications. J Tissue Eng Regen Med. 2013;7:353–61. https://doi.org/10.1002/term.530.

    Article  PubMed  CAS  Google Scholar 

  81. Walsh WR, Oliver RA, Christou C, Lovric V, Walsh ER, Prado GR, et al. Critical size bone defect healing using collagen–calcium phosphate bone graft materials. PLoS One. 2017;12(1):e0168883. https://doi.org/10.1371/journal.pone.0168883.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Palmer I, Nelson J, Schatton W, Dunne NJ, Buchanan F, Clarke SA. Biocompatibility of calcium phosphate bone cement with optimised mechanical properties. J Biomed Mater Res B Appl Biomater. 2015:1–8. https://doi.org/10.1002/jbm.b.33370.

  83. Maas M, Guo P, Keeney M, et al. Preparation of mineralized nanofibers: collagen fibrils containing calcium phosphate. Nano Lett. 2011;11:1383–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Kikuchi M, Itoh S, Ichinose S, Shinomiya K, Tanaka J. Self-organization mechanism in a bone-like hydroxyapatite/collagen nanocomposite synthesized in vitro and its biological reaction in vivo. Biomaterials. 2001;22:1705–11.

    Article  PubMed  CAS  Google Scholar 

  85. Aberg J, Brisby H, Henriksson HB, et al. Premixed acidic calcium phosphate cement: characterization of strength and microstructure. J Biomed Mater Res B. 2010;93(2):436–41.

    Article  CAS  Google Scholar 

  86. Carey LE, Xu HH, Simon CG, et al. Premixed rapid-setting calcium phosphate composites for bone repair. Biomaterials. 2005;26(24):5002–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Takagi S, Chow LC, Hirayama S, et al. Premixed calcium–phosphate cement pastes. J Biomed Mater Res B. 2003;67(2):689–96.

    Article  CAS  Google Scholar 

  88. Tozzi G, Mori A, Oliveira A, Roldo M. Composite hydrogels for bone regeneration. Materials. 2016;9:267. https://doi.org/10.3390/ma9040267.

    Article  PubMed Central  CAS  Google Scholar 

  89. Short AR, et al. Hydrogels that allow and facilitate bone repair, remodeling, and regeneration. J Mater Chem B Mater Biol Med. 2015;3(40):7818–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Planell JA, Best SM, Lacroix D, Merolli A. Bone repair biomaterials. Amsterdam: CRC Press, Elsevier; 2009.

    Book  Google Scholar 

  91. Nedde AT, Julich-Gruner KK, Leindlein A. Combinations of biopolymers and synthetic polymers for bone regeneration. Chapter 4. In: Dubruel P, Vlierberghe SV, editors. Biomaterials for bone regeneration: novel techniques and applications. Amsterdam: Elsevier; 2014. p. 87–110. https://doi.org/10.1533/9780857098104.1.87.

    Chapter  Google Scholar 

  92. Susana Cortizo M, Soledad Belluzo M. Biodegradable polymers for bone tissue engineering. In: Goyanes N, D’Accorso NB, editors. Industrial applications of renewable biomass products. Berlin: Springer International Publishing AG; 2017. p. 47–74S. https://doi.org/10.1007/978-3-319-61288-1_2.

    Chapter  Google Scholar 

  93. Kroeze RJ, Helder MN, Govaert LE, Smit TH. Biodegradable polymers in bone tissue engineering. Mater. 2009;2:833–56. https://doi.org/10.3390/ma2030833.

    Article  CAS  Google Scholar 

  94. Sheikh Z, Najeeb S, Khurshid Z, Verma V, Rashid H, Glogauer M. Biodegradable materials for bone repair and tissue engineering applications. Mater. 2015;8(9):5744–94. https://doi.org/10.3390/ma8095273.

    Article  CAS  Google Scholar 

  95. Engstrand J, Persson C, Engqvist H. Influence of polymer addition on the mechanical properties of premixed calcium phosphate cement. Biomatter. 2013;3(4):e27249. https://doi.org/10.4161/biom.27249.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Geffers M, Groll J, Gbureck U. Reinforcement strategies for load-bearing calcium phosphate biocements. Materials. 2015;8:2700–17. https://doi.org/10.3390/ma8052700.

    Article  PubMed Central  CAS  Google Scholar 

  97. Sun J, Tan H. Alginate-based biomaterials for regenerative medicine applications. Materials. 2013;6:1285–308.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Wang L, Wang P, Weir MD, et al. Hydrogel fibers encapsulating human stem cells in an injectable calcium phosphate scaffold for bone tissue engineering. Biomed Mater. 2016;11:065008.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Venkstesan J, Nithya R, Kim SK. Role of alginate in bone tissue engineering. Adv Food Nutr Res. 2014;73:45–57.

    Article  CAS  Google Scholar 

  100. Venkatesan J, Bhatnagarb I, Manivasagana P, Kanga K-H, Kima SK. Alginate composites for bone tissue engineering: a review. Int J Biol Macromol. 2015;72:269–81.

    Article  PubMed  CAS  Google Scholar 

  101. Zhao L, Weir MD, Xu HHK. An injectable calcium phosphate-alginate hydrogel-umbilical cord mesenchymal stem cell paste for bone tissue engineering. Biomaterials. 2010;31:6502–10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Thein-Han WW, WahWah MD, Weir CG, Wu HH. Novel non-rigid calcium phosphate scaffold seeded with umbilical cord stem cells for bone tissue engineering. J Tiss Eng Regen. 2013;7(10):777–87.

    CAS  Google Scholar 

  103. Wang X, Chen L, Xiang H, et al. Influence of anti-washout agents on the rheological properties and injectability of a calcium phosphate. J Biomed Mater Res B. 2007;81(2):410–8.

    Article  CAS  Google Scholar 

  104. Karnik S, Jammalamadaka U, Tappa K, Mills DK. Performance evaluation of nanoclay enriched anti-microbial hydrogels for biomedical applications. Heliyon. 2016;2(2):e00072. https://doi.org/10.1016/j.heliyon.2016.e00072.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Karnik S, Mills DK. Nanoenhanced hydrogel system with sustained release capabilities. J Biomed Mater Res A. 2015;103(7):2416–26.

    Article  PubMed  CAS  Google Scholar 

  106. Wang P, Song Y, Weir MD, Sun J, Zhao L, Simon CG, Xu HH, et al. A self-setting iPSMSC-alginate-calcium phosphate paste for bone tissue engineering. Dental mater. 2018;32(2):252–63.

    Article  CAS  Google Scholar 

  107. Costa-Pinto AR, Reis RL, Neves NM. Scaffolds based bone tissue engineering: the role of chitosan. Tiss Eng B Rev. 2011;17:331–47.

    Article  CAS  Google Scholar 

  108. Muzzarelli RAA. Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone. Carbohydr Polym. 2009;76:167182.

    Article  CAS  Google Scholar 

  109. Oliveira JM, Rodrigues MT, Silva SS, Malafaya PB, Gomes ME, Viegas CA, et al. Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue engineering applications: scaffold design and its performance when seeded with goat bone marrow stromal cells. Biomaterials. 2006;27:6123–37.

    Article  PubMed  CAS  Google Scholar 

  110. Zeng S, Liu L, Shi Y, Qiu J, Fang W, Rong M, Guo Z, Gao W. Characterization of silk fibroin/chitosan 3D porous scaffold and in vitro cytology. PLoS One. 2015;10(6):e0128658. Epub 2015 Jun 17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Li J, Wang Q, Gu Y, Zhu Y, Chen L, Chen Y. Production of composite scaffold containing silk fibroin, chitosan, and gelatin for 3D cell culture and bone tissue regeneration. Med Sci Monit. 2017;23:5311–20.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Frihberg ME, Katsman A, Mondrinos MJ, Stabler CT, Hankenson KD, Oristaglio JT, Lelkes PI. Osseointegrative properties of electrospun hydroxyapatite-containing nanofibrous chitosan scaffolds. Tissue Eng Part A. 2015;21(5–6):979–81.

    Google Scholar 

  113. Zhang Y, Reddy VJ, Wong SY, Li X, Su B, Ramakrishna S, et al. Enhanced biomineralization in osteoblasts on a novel electrospun biocomposite nanofibrous substrate of hydroxyapatite/collagen/chitosan. Tissue Eng Part A. 2010;16:1949–60.

    Article  PubMed  CAS  Google Scholar 

  114. Venugopal J, Low S, Choon AT, Sampath Kumar TS, Ramakrishna S. Mineralization of osteoblasts with electrospun collagen/hydroxyapatite nanofibers. J Mater Sci Mater Med. 2008;19:2039–46.

    Article  PubMed  CAS  Google Scholar 

  115. Wnek GE, Bowlin GL. Encyclopedia of biomaterials and biomedical engineering. New York: Marcel Dekker; 2004.

    Google Scholar 

  116. Bleek K, Taubert A. New developments in polymer-controlled, bioinspired calcium phosphate mineralization from aqueous solution. Acta Biomater. 2013;9(5):6283–321.

    Article  PubMed  CAS  Google Scholar 

  117. Ratner BD, Hoffman AS, Schoen FJ, Lemons JE. Biomaterials science: aintroduction to materials in medicine. 2nd ed. London: Elsevier Academic Press; 2004.

    Google Scholar 

  118. Rebelo R, Fernandesa M, Fangueiroa R. Biopolymers in medical implants: a brief review. Process Eng. 2017;200:236–43.

    CAS  Google Scholar 

  119. Tereshchenko VP, Kirlova A, Sadavoy MA, Larionov PM. The materials used in bone tissue engineering. In: AIP Conference Proceedings. vol. 1688, 030022; 2015. doi: https://doi.org/10.1063/1.4936017

  120. Melinda Molnar R, Bodnar M, Hartmann JF, Borbely J. Preparation and characterization of poly(acrylic acid)-based nanoparticles. Coll Poly Sci. 2009;287(6):739–44.

    Article  CAS  Google Scholar 

  121. Verma D, Katti K, Mohanty B. Mechanical properties of biomimetic composites for bone tissue engineering. MRS Proc. 2004;844:Y6.2. https://doi.org/10.1557/PROC-844-Y6.2.

    Article  Google Scholar 

  122. Stevens B, Yang Y, Mohandas A, Stucker B, Nguyen KT. A review of materials, fabrication method and strategies used to enhance bone regeneration. J Biomed Mater Res. 2008;85B:573–82.

    Article  CAS  Google Scholar 

  123. He H, Qiao Z, Liu C. Accelerating biodegradation of calcium phosphate cement. In: Liu C, He H, editors. Developments and applications of calcium phosphate bone cements, Chapter. 5. Singapore: Springer; 2018. p. 227–56.

    Chapter  Google Scholar 

  124. Shim J-H, Moon T-S, Yun M-J, Jeon Y-C, Jeong C-M, Cho D-W, Huh J-B. Stimulation of healing within a rabbit calvarial defect by a PCL/PLGA scaffold blended with TCP using solid freeform fabrication technology. J Mater Sci Mater Med. 2012;23:2993–3002.

    Article  PubMed  CAS  Google Scholar 

  125. Park SA, Lee SH, Kim WD. Fabrication of porous polycaprolactone/hydroxyapatite (PCL/HA) blend scaffolds using a 3D plotting system. Bioprocess Biosyst Eng. 2011;34:505. https://doi.org/10.1007/s00449-010-0499-2.

    Article  PubMed  CAS  Google Scholar 

  126. Liao HT, Lee MY, Tsai WW, Wang HV, Lu WC. Osteogenesis of adipose-derived stem cells on polycaprolactone-β-tricalcium phosphate scaffold fabricated via selective laser sintering and surface coating with collagen type I. J Tissue Eng Regen Med. 2016;10(10):E337–53. https://doi.org/10.1002/term.1811. Epub 2013 Aug 16.

    Article  PubMed  CAS  Google Scholar 

  127. Nyberg E, Rindone A, Dorafshar A, Grayson WL. Comparison of 3D-printed poly-ɛ-caprolactone scaffolds functionalized with tricalcium phosphate, hydroxyapatite, Bio-Oss, or Decellularized Bone Matrix. Tissue Eng Part A. 2017;23(11–12):503–14.

    Article  PubMed  CAS  Google Scholar 

  128. http://www.bioinksolutions.com/

  129. Ghosh SB, Bandyopadhyay-Ghosh S, Sain M. Composites. Chapter 18. In: Auras R, Lim L-T, Selke SEM, Tsuji H, editors. Poly(lactic acid): synthesis, structures, properties, processing, and applications. Hoboken, NJ: Wiley; 2010. https://doi.org/10.1002/9780470649848.

    Chapter  Google Scholar 

  130. Adeosun SO, Lawal GI, Gbenebor P. Characteristics of biodegradable implants. J Min Mater Charact Eng. 2014;2:88–106.

    CAS  Google Scholar 

  131. Rajendran T, Venugopalan S. Role of polylactic acid in bone regeneration–a systematic review. J Pharm Sci Res. 2015;7(11):960–6.

    CAS  Google Scholar 

  132. Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR. Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials. 2006;27(18):3413–31.

    Article  PubMed  CAS  Google Scholar 

  133. Tanataweethum N, Liu W, Goebel W, Li D, Chu T. Fabrication of poly-l-lactic acid/dicalcium phosphate dihydrate composite scaffolds with high mechanical strength—implications for bone tissue engineering. J Funct Mater. 2015;6(4):1036–53. https://doi.org/10.3390/jfb6041036.

    Article  CAS  Google Scholar 

  134. Liu X, Liu H-Y, Lian X, Shi X-L, Wang W, Cui F-Z, Zhang Y. Osteogenesis of mineralized collagen bone graft modified by PLA and calcium sulfate hemihydrate: in vivo study. J Biomater Appl. 2012;28(1):12–9.

    Article  PubMed  CAS  Google Scholar 

  135. Montjovent M-O, Silke S, Mathieu L, Scaletta C, Scherberich S, et al. Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering. Bone. 2008;42:554–64.

    Article  PubMed  CAS  Google Scholar 

  136. Lou C-W, Chen W-C, Luo C-T, Huang C-C, Lin JH. Compressive strength of porous bone cement/polylactic acid composite bone scaffolds. Appl Mech Mater. 2013;365-366:1062–5.

    Article  CAS  Google Scholar 

  137. Danoux CB, Barberi D, Yuan H, de Brulin JD, van Blitterswilk CA, et al. In vitro and in vivo bioactivity assessment of a polylactic acid/hydroxyapatite composite for bone regeneration. Biomaterials. 2014;4:e27664. PMC Web 22 Feb. 2018.

    Google Scholar 

  138. Gentile P, Chiono V, Carmagnola I, Hatton PV. An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering. Intern J Mol Sci. 2014;15(3):3640–59. https://doi.org/10.3390/ijms15033640.

    Article  CAS  Google Scholar 

  139. Sun X, Chu X, Ye Q, Wang C. Poly(lactic-co-glycolic acid): applications and future prospects for periodontal tissue regeneration. Polymers. 2017;9:189. https://doi.org/10.3390/polym9060189.

    Article  CAS  PubMed Central  Google Scholar 

  140. Ortega-Oiler I, Padial-Molina M, Galindo-Moreno P, O’Valle F, et al. Bone regeneration from PLGA micro-nanoparticles. Biomed Res Int. 2015;2015:415289. https://doi.org/10.1155/2015/415289.

    Article  CAS  Google Scholar 

  141. Kane RJ, Weiss-Bilka HE, Meagher MJ, et al. Hydroxyapatite reinforced collagen scaffolds with improved architecture and mechanical properties. Acta Biomater. 2015;17:16–25. https://doi.org/10.1016/j.actbio.2015.01.031.

    Article  PubMed  CAS  Google Scholar 

  142. Demirci DS, Bayir Y, Halici Z, Karakus E, et al. Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering. Mater Sci Eng C. 2014;44:246–53. https://doi.org/10.1016/j.msec.2014.08.035.

    Article  CAS  Google Scholar 

  143. Mousa M, Evans ND, Oreffo ROC, Lawson JI. Clay nanoparticles for regenerative medicine and biomaterial design: a review of clay bioactivity. Biomaterials. 2018;159:204–14. https://doi.org/10.1016/j.biomaterials.2017.12.024.

    Article  PubMed  CAS  Google Scholar 

  144. Ruiz-Hitzky E, Aranda P, Dardera M, Rytwobc G. Hybrid materials based on clays for environmental and biomedical applications. J Mater Chem. 2010;20:9306–21.

    Article  CAS  Google Scholar 

  145. Newman P, Minett HA, Ellis-Behnke R, Zreiqat H. Carbon nanotubes: their potential and pitfalls for bone tissue regeneration and engineering. Nanomedicine. 2013;9(8):1139–58.

    Article  PubMed  CAS  Google Scholar 

  146. Tanaka M, Sato Y, Haniu H, Sato H, et al. A three-dimensional block structure consisting exclusively of carbon nanotubes serving as bone regeneration scaffold and as bone defect filler. PLoS One. 2017;12(2):e0172601. https://doi.org/10.1371/journal.pone.0172601.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Mukharjee S, Kumar S, Kundu B, Chanda A, Sen S, Das PK. Enhanced bone regeneration with carbon nanotube reinforced hydroxyapatite in animal model. J Mech Behav Biomed Mater. 2016;60:243–55.

    Article  CAS  Google Scholar 

  148. Venkatesan J, Pallela R, Kim SK. Applications of carbon nanomaterials in bone tissue engineering. J Biomed Nanotechnol. 2014;10:3105–23.

    Article  PubMed  CAS  Google Scholar 

  149. Liu M, Jia Z, Jia D, Zhou C. Recent advance in research on halloysite nanotubes-polymer nanocomposite. Prog Polym Sci. 2014;39:1498–525.

    Article  CAS  Google Scholar 

  150. Leporatti S. Halloysite clay nanotubes as nano-bazookas for drug delivery. Polym Int. 2017;66:1111–8. https://doi.org/10.1002/pi.5347.

    Article  CAS  Google Scholar 

  151. Fan L, Zhang J, Wang A. In situ generation of sodium alginate/hydroxyapatite/halloysite nanotubes nanocomposite hydrogel beads as drug-controlled release matrices. J Mater Chem B. 2013;1:6261–70.

    Article  CAS  PubMed  Google Scholar 

  152. Lvov Y, Wang W, Zhang L, Fakhrullin R. Halloysite clay nanotubes for loading and sustained release of functional compounds. Adv Mater. 2016;28:1227–50.

    Article  PubMed  CAS  Google Scholar 

  153. Mills DK, Jammalamadaka U, Tappa UK, Weisman JA. Studies on the cytocompatibility, mechanical and antimicrobial properties of 3D printed poly(methyl methacrylate) beads. Bioactive Mater. 2018;3(1):157–66.

    Article  Google Scholar 

  154. Naumenko EA, Guryanov ID, Yendluri R, Lvov YM, Fakhrullin RF. Clay nanotube-biopolymer composite scaffolds for tissue engineering. Nanoscale. 2016;8:7257–71.

    Article  PubMed  CAS  Google Scholar 

  155. Liu M, Wu C, Jiao Y, Xiong S, Zhou C. Chitosan-halloysite nanotubes nanocomposite scaffolds for tissue engineering. J Mater Chem B. 2013;1:2078–89.

    Article  CAS  PubMed  Google Scholar 

  156. Massaro M, Lazzara G, Milioto S, Noto R, Riela S. Covalently modified halloysite clay nanotubes: synthesis, properties, biological and medical applications. J Mater Chem B. 2017;5:2867–82.

    Article  CAS  PubMed  Google Scholar 

  157. Jammalamadaka U, Tappa K, Mills DK. Calcium phosphate/clay nanotube bone cement with enhanced mechanical properties and sustained drug release. In: Zoveidavianpoor M, editor. Clay science and engineering. London: InTech Publishers. (in press) Publication date: May 2018.

    Google Scholar 

  158. Karnik S, Mills DK. Clay nanotubes as growth factor delivery vehicle for bone tissue engineering. J Nanomed Nanotechnnol. 2013;4(6):102.

    Google Scholar 

  159. Tappa K, Jammalamadaka U, Mills DK. Formulation and evaluation of nanoenhanced anti-bacterial calcium phosphate bone cements. In: Webster T, Li B, editors. Orthopedic biomaterials. New York, NY: Springer. (in press) May 2018.

    Google Scholar 

  160. Tomas H, Alves CS, Rodrigues J. Laponite®: a key nanoplatform for biomedical applications?. Nanomed Nanotech Biol Med. 2017, in press.

    Google Scholar 

  161. Jung H, Kim HM, Choy YB, Hwang SJ, Choy JH. Itraconazole-laponite: kinetics and mechanism of drug release. Appl Clay Sci. 2008;40(1–4):99–107.

    Article  CAS  Google Scholar 

  162. Wang C, Wang S, Li K, Lu Y, Li J, Zhang Y, Li J, Liu X, Shi X, Zhao Q. Preparation of laponite bioceramics for potential bone tissue engineering applications. PLoS One. 2014;23:e99585. https://doi.org/10.1371/journal.pone.0099585.

    Article  CAS  Google Scholar 

  163. Xavier JR, Thakur T, Desai P, Jaiswal MK, Sears N, Cosgriff-Hernandez E, Kaunas R, Gaharwar AK. Bioactive nanoengineered hydrogels for bone tissue engineering: a growth-factor-free approach. ACS Nano. 2015;9(3):3109–18. https://doi.org/10.1021/nn507488s.

    Article  PubMed  CAS  Google Scholar 

  164. Thorpe A, Freeman C, Farthing P,Hatton P, Brook I, Sammon C, Le Maitre CL. Osteogenic differentiation of human mesenchymal stem cells in hydroxyapatite loaded thermally triggered, injectable hydrogel scaffolds to promote repair and regeneration of bone defects. In: Frontiers in bioengineering and biotechnology. Conference abstract: 10th world biomaterials congress; 2016. doi: 10.3389/conf.FBIOE.2016.01.00636

    Google Scholar 

  165. Tao L, Zhonglong L, Ming X, Zezheng Y, Zhiyuan L, Xiaojun Z. In vitro and in vivo studies of a gelatin/carboxymethyl chitosan/LAPONITE® composite scaffold for bone tissue engineering. RSC Adv. 2017;7:54100.

    Article  CAS  Google Scholar 

  166. Jayrajsinh S, Shankar G, Agrawal YK, Bakre L. Montmorillonite nanoclay as a multifaceted drug-delivery carrier: a review. J Drug Delivery Sci Technol. 2017;39:200–9.

    Article  CAS  Google Scholar 

  167. Aguzzi C, Cerezo P, Viseras C, Caramella C. Use of clays as drug delivery systems: possibilities and limitations. Appl Clay Sci. 2007;36:22–36. https://doi.org/10.1016/j.clay.2006.06.015.

    Article  CAS  Google Scholar 

  168. Baker KC, Maerz T, Saad H, Shaheen P, Kannan RM. In vivo bone formation by and inflammatory response to resorbable polymer-nanoclay constructs. Nanomedicine. 2015;11(8):1871–81. https://doi.org/10.1016/j.nano.2015.06.012. Epub 2015 Jul 26.

    Article  PubMed  CAS  Google Scholar 

  169. Olad A, Azhar FF. The synergetic effect of bioactive ceramic and nanoclay on the properties of chitosan–gelatin/nanohydroxyapatite–montmorillonite scaffold for bone tissue engineering. Ceram Int. 2014;40(7):10061–72.

    Article  CAS  Google Scholar 

  170. Kar S, Kaur T, Thirugnanam A. Microwave-assisted synthesis of porous chitosan–modified montmorillonite–hydroxyapatite composite scaffolds. Inter J Biol Macromol. 2016;82:628–36.

    Article  CAS  Google Scholar 

  171. Kwon SY, Cho EH, Kim SS. Preparation and characterization of bone cements incorporated with montmorillonite. J Biomed Mater Res. 2007;83B:276–84. https://doi.org/10.1002/jbm.b.30793.

    Article  CAS  Google Scholar 

  172. Sharma C, Dinda AK, Potdar PD, Chu C-F, Mishra NC. Fabrication and characterization of novel nano-biocomposite scaffold of chitosan–gelatin–alginate–hydroxyapatite for bone tissue engineering. Mater Sci Eng C. 2016;64:416–27.

    Article  CAS  Google Scholar 

  173. Hamzah AA, Selvarajan RS, Majlis BY. Graphene for biomedical applications: a review. Sains Malaysiana. 2017;46(7):1125–39. https://doi.org/10.17576/jsm-2017-4607-16.

    Article  Google Scholar 

  174. Pattnaik S, Swain K, Linc Z. Graphene and graphene-based nanocomposites: biomedical applications and biosafety. J Mater Chem B. 2016;4:7813–31.

    Article  CAS  PubMed  Google Scholar 

  175. Nasrin S, Hasanzadeh M. Graphene and its nanostructure derivatives for use in bone tissue engineering: recent advances. J Biomed Mater Res Part A. 2016;104A:1250–75.

    Google Scholar 

  176. Reina G, Criado A, Prato M, Gonzalez-Domınguez JM, Vazques E, Bianco A. Promises, facts and challenges for graphene in biomedical applications. Chem Soc Rev. 2017;46:4400–16.

    Article  PubMed  CAS  Google Scholar 

  177. Kalbacova M, Bronz A, Kong J, Kalbac M. Graphene substrates promote adherence of human osteoblasts and mesenchymal stromal cells. Carbon. 2010;48:4323–9.

    Article  CAS  Google Scholar 

  178. Nayak TR, Andersen H, Makam VS, Khaw C, Bae S, Xu X, P-LR E, Ahn JH, Hong BH, Pastorin G. Graphene for controlled and accelerated osteogenic differentiation of human mesenchymal stem cells. ACS Nano. 2011;5(6):4670–8.

    Article  PubMed  CAS  Google Scholar 

  179. Dubey N, Bentini R, Islam I, Cao T, Neto AHC, Rosa V. Graphene: a versatile 531 carbon-based material for bone tissue engineering. Stem Cells Int. 2015;2015:804213.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Tommila M, Jokilammi A, Penttinen R, Ekholm E. Cellulose—a biomaterial with cell-guiding property. In: van de Ven T, Godbout L. Cellulose-medical, pharmaceutical and electronic applications, chapter 5. Croatia: InTech. ISBN: 978-953-51-1191-7. 314 pages.

    Google Scholar 

  181. Beladia F, Saber-Samandarib S, Saber-Samandaric S. Cellular compatibility of nanocomposite scaffolds based on hydroxyapatite entrapped in cellulose network for bone repair. Mater Sci Eng C. 2017;75:385–92.

    Article  CAS  Google Scholar 

  182. Teti G, Orsini G, Mazzotti A, Belmonte M, Ruggeri A. 3D polysaccharide based hydrogel for bone tissue engineering. Ital J Anat Embryol. 2015;120(1):129. https://doi.org/10.13128/IJAE-17000.

    Article  Google Scholar 

  183. Novotna K, Havelka P, Sopuch T, Kolarova K, et al. Cellulose-based materials as scaffolds for tissue engineering. Cellulose. 2013;20(5):2263–78.

    Article  CAS  Google Scholar 

  184. Aravamudhan A, Ramos DM, Nip J, Kalajzic I, Kumbar SG. Micro-nanostructures of cellulose-collagen for critical sized bone defect healing. Macromol Biosci. 2018;18(2). https://doi.org/10.1002/mabi.201700263. Epub 2017 Nov 27.

  185. Moreau JL, Weir MD, Xu HH. Self-setting collagen-calcium phosphate bone cement: mechanical and cellular properties. J Biomed Mater Res. 2009;91A:605–13.

    Article  CAS  Google Scholar 

  186. Kikuchi M, Ikoma T, Itoh S, Matsumoto HN, Koyama Y, Takakuda K, Shinomiya K, Tanaka J. Biomimetic synthesis of bone-like nanocomposites using the self-organization mechanism of hydroxyapatite and collagen. Compos Sci Technol. 2004;64(6):819–25.

    Article  CAS  Google Scholar 

  187. Kikuchi M. Hydroxyapatite/collagen bone-like nanocomposite. Biol Pharm Bull. 2013;36(11):1666–9.

    Article  PubMed  Google Scholar 

  188. Sarkar SK, Lee BT. Hard tissue regeneration using bone substitutes: an update on innovations in materials. Korean J Intern Med. 2015;30:279–93. https://doi.org/10.3904/kjim.2015.30.3.279.

    Article  PubMed  PubMed Central  Google Scholar 

  189. Bohner M, Baroud G. Injectability of calcium phosphate pastes. Biomaterials. 2005;26:1553–63.

    Article  PubMed  CAS  Google Scholar 

  190. Blokhuis TJ. Formulations and delivery vehicles for bone morphogenetic proteins: latest advances and future directions. Injury. 2009;40(Suppl 3):S8–11.

    Article  PubMed  Google Scholar 

  191. Kretlow JD, Young S, Klouda L, Wong M, Mikos AG. Injectable biomaterials for regenerating complex craniofacial tissues. Adv Mater. 2009;21:3368–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Liu M, Zeng X, Ma C, Yi H, Zeeshan A, et al. Injectable hydrogels for cartilage and bone tissue engineering. Bone Research. 2017;5:17014–32. PMC. Web 27 Feb. 2018.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  193. Chen L, Shen R, Komasa S, Xue Y, et al. Drug-loadable calcium alginate hydrogel system for use in oral bone tissue repair. In: Hardy JG, editor. Inter J Mol Sci. 2017; 8(5): 989. PMC. Web. 27 Feb 2018.

    Google Scholar 

  194. Bi L, Cheng W, Fan H, Pei G. Reconstruction of goat tibial defects using an injectable tricalcium phosphate/chitosan in combination with autologous platelet-rich plasma. Biomaterials. 2010;31(12):3201–11.

    Article  PubMed  CAS  Google Scholar 

  195. Martínez-Sanz E, Ossipov DA, Hilborn J, Larsson S, Jonsson KB, Varghese OP. Bone reservoir: injectable hyaluronic hydrogels for minimal invasive bone augmentation. J Cont Rel. 2011;152(2):232–40.

    Article  CAS  Google Scholar 

  196. Hanninka G, Chris Arts JJ. Bioresorbability, porosity and mechanical strength of bone substitutes: what is optimal for bone regeneration? Injury. 2011;42(Suppl. 2):S22–5.

    Article  Google Scholar 

  197. Yasmeen S, lo MK, Bajarcharya S, Roldo M. Injectable scaffolds for bone regeneration. Langmuir. 2014;30(43):12977–85. https://doi.org/10.1021/la503057w.

    Article  PubMed  CAS  Google Scholar 

  198. Polo-Corrales L, Latorre-Esteves M, Ramirez JE. Scaffold design for bone regeneration. J Nanosci Nanotechnol. 2014;14(1):15–56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  199. Devescovi V, Leonardi E, Ciapetti G, Cenni E. Growth factors in bone repair. Musculoskel Surg. 2008;92:161–8.

    Google Scholar 

  200. Vo TN, Kasper FK, Mikos AG. Strategies for controlled delivery of growth factors and cells for bone regeneration. Adv Drug Deliv Rev. 2012;64(12):1292–309. https://doi.org/10.1016/j.addr.2012.01.016.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  201. Rahman CV, Ben-David D, Dhillon A, Kuhn G, Gould TW, et al. Controlled release of BMP-2 from a sintered polymer scaffold enhances bone repair in a mouse calvarial defect model. J Tissue Eng Regen Med. 2014;8(1):59–66.

    Article  PubMed  CAS  Google Scholar 

  202. Santo VE, Gomes ME, Mano JF, Reis RL. Controlled release strategies for bone, cartilage, and osteochondral engineering—Part II: challenges on the evolution from single to multiple bioactive factor delivery. Tissue Eng B Rev. 2013;19(4):327–52. https://doi.org/10.1089/ten.teb.2012.0727.

    Article  CAS  Google Scholar 

  203. Majewski RL, Zhang W, Ma X, Ciu A, Ren W, Markel DC. Bioencapsulation technologies in tissue engineering. J Appl Biomater Funct Mater. 2016;14(4):e395–403. https://doi.org/10.5301/jabfm.5000299.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  204. Nicodemus GD, Bryant SJ. Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng B Rev. 2008;14(2):149–65. https://doi.org/10.1089/ten.teb.2007.0332.

    Article  CAS  Google Scholar 

  205. Jimi E, Hirata S, Osawa K, Terashita M, Kitamura C, Fukushima H. The current and future therapies of bone regeneration to repair bone defects. Int J Dent. 2012;2012: 148261, 7 pages. doi:https://doi.org/10.1155/2012/148261.

  206. Kolambkara YM, Dupont KM, Boerckle JD, Huebsch N, Mooney DJ, et al. An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. Biomaterials. 2011;32(1):65–74.

    Article  CAS  Google Scholar 

  207. Bendtsen ST. Alginate hydrogels for bone tissue regeneration. 2017. Doctoral Dissertations. 1409.http://digitalcommons.uconn.edu/dissertations/1409

  208. Kim J, Kim IS, Cho TH, Lee KB, Hwang SJ, et al. Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials. 2007;28(10):1830–7.

    Article  PubMed  CAS  Google Scholar 

  209. Włodarczyk-Biegun MK, Farbod K, Werten MWT, Slingerland CJ, de Wolf FA, van den Beucken JP, et al. Fibrous hydrogels for cell encapsulation: a modular and supramolecular approach. PLoS One. 2016;11(5):e0155625. https://doi.org/10.1371/journal.pone.0155625.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  210. Hamlet SM, Vaquette C, Shah A, Hutmacher DW, Ivanovski S. 3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering. J Clin Periodontol. 2017;44(4):428–37. https://doi.org/10.1111/jcpe.12686.

    Article  PubMed  CAS  Google Scholar 

  211. Burdick JA, Anseth K. Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials. 2002;23(22):4513–23.

    Article  Google Scholar 

  212. Yamamuro Y, Hench LL, Wilson J. Bioactive glasses and glass ceramics. In: Handbook of bioactive ceramics, vol. 1. Boca Raton: CRC Press; 1990.

    Google Scholar 

  213. Vallet-Regí M, Ruiz-González L, Izquierdo-Barba I, et al. Revisiting silica based ordered mesoporous materials: medical applications. J Mater Chem. 2006;16:26–31.

    Article  Google Scholar 

  214. Gerhardt L-C, Boccaccini AR. Bioactive glass and glass-ceramic scaffolds for bone tissue engineering. Materials. 2010;3:3867–910. https://doi.org/10.3390/ma3073867.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  215. Kim HW, Kim HE, Knowles JC. Production and potential of bioactive glass nanofibers as a next-generation biomaterial. Adv Funct Mater. 2006;16(12):1529–35. https://doi.org/10.1002/adfm.200500750.

    Article  CAS  Google Scholar 

  216. Christkiran, Reardon PJ, Konwarh R, Knowles JC, Mandal BB. Mimicking hierarchical complexity of the osteochondral interface using electrospun silk–bioactive glass composites. ACS Appl Mater Interfac. 2017;9(9):8000–13.

    Article  CAS  Google Scholar 

  217. Price CT, Koval KJ, Langford JR. Silicon: a review of Its potential role in the prevention and treatment of postmenopausal osteoporosis. Int J Endocrinol. 2013;2013:316783., 6 pages. https://doi.org/10.1155/2013/316783.

    Article  PubMed  PubMed Central  Google Scholar 

  218. Price CT, Langford JR, Liporace FA. Essential nutrients for bone health and a review of their availability in the average North American diet. Open Orthopaed J. 2012;6:143–9.

    Article  Google Scholar 

  219. Rodrigues AI, Reis RL, van Blitterswijk CA, Leonor IB, Habibović P. Calcium phosphates and silicon: exploring methods of incorporation. Biomater Res. 2017;21(6):1–11.

    Google Scholar 

  220. Izquierdo-Barba I, Colilla M, Vallet-Regí M. Nanostructured mesoporous silicas for bone tissue regeneration. J Nanomat. 2008, . 2008: 106970, 14 pages. doi: 10.1155/2008/106970.

    Google Scholar 

  221. Yan X, Yu C, Zhou X, Tang J, Zhao D. Highly ordered mesoporous bioactive glasses with superior in vitro bone-forming bioactivities. Angew Chem Int. 2004;43(44):5980–4.

    Article  CAS  Google Scholar 

  222. Parra J, García Páez IH, De Aza AH, Baudin C, Rocío Martín MM, Pena P. In vitro study of the proliferation and growth of human fetal osteoblasts on Mg and Si co-substituted tricalcium phosphate ceramics. J Biomed Mater Res Part A. 2017;105A:2266–75.

    Article  CAS  Google Scholar 

  223. Aparicio JL, Rueda C, Manchon A, et al. Effect of physicochemical properties of a cement based on silicocarnotite/calcium silicate on in vitro cell adhesion and in vivo cement degradation. Biomed Mater. 2016;11:045005.

    Article  PubMed  CAS  Google Scholar 

  224. Yu L, Li Y, Zhao K, Tang Y, Cheng Z, Chen J, Wu Z. A novel injectable calcium phosphate cement-bioactive glass composite for bone regeneration. PLoS One. 2013;8(4):e62570. https://doi.org/10.1371/journal.pone.0062570.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  225. Zhou X, Zhang N, Mankoci S, Sahai N. Silicates in orthopedics and bone tissue engineering materials. J Biomed Mater Res Part A. 2017;105A:2090–102.

    Article  CAS  Google Scholar 

  226. Bose S, Fielding G, Tarafder S, Bandyopadhyay A. Understanding of dopant-induced osteogenesis and angiogenesis in calcium phosphate ceramics. Trends in Biotechnol. 2013;31:594–605. https://doi.org/10.1016/j.tibtech.2013.06.005.

    Article  CAS  Google Scholar 

  227. Tran N, Webster TJ. Increased osteoblast functions in the presence of hydroxyapatite-coated iron oxide nanoparticles. Acta Biomater. 2011;7(3):1298–306.

    Article  PubMed  CAS  Google Scholar 

  228. Midde S. Osteoblast functionality on bioactive TiO2 nanosubstrates. MS Thesis, Louisiana Tech University, Ruston LA. 71272.

    Google Scholar 

  229. Goto K, et al. Bioactive bone cements containing nano-sized titania particles for use as bone substitutes. Biomaterials. 2005;26(33):6496–505.

    Article  PubMed  CAS  Google Scholar 

  230. Shiad M, Chen Z, Farnaghib S, Friis T, Mao X, et al. Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis. Acta Biomater. 2015;30:334–44.

    Google Scholar 

  231. Swetha M, Sahithi K, Moorthi A, Saranya N, Saravanan S, et al. Synthesis, characterization, and antimicrobial activity of nano-hydroxyapatite-zinc for bone tissue engineering applications. J Nanosci Nanotechnol. 2012;12:167–72.

    Article  PubMed  CAS  Google Scholar 

  232. Baria A, Bloisebec N, Firilla S, Novajraa G, Vaellet-Regid M, et al. Copper-containing mesoporous bioactive glass nanoparticles as multifunctional agent for bone regeneration. Acta Biomater. 2017;55:493–504.

    Article  CAS  Google Scholar 

  233. Ishimi Y. Nutrition and bone health. Magnesium and bone. Clin Calc. 2010, 20(5): 762–7. CliCa1005762767.

    Google Scholar 

  234. Weng L, Webster TJ. Nanostructured magnesium has fewer detrimental effects on osteoblast function. Int J Nanomedicine. 2013;8:1773–81. https://doi.org/10.2147/IJN.S39031.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  235. Staiger MP, Pietak AM, Huadmai J, Dias G. Magnesium and its alloys as orthopedic biomaterials: a review. Biomaterials. 2006;27:1728–34. https://doi.org/10.1016/j.biomaterials.2005.10.003.

    Article  PubMed  CAS  Google Scholar 

  236. Malladi L, Mahapatro A, Gomes AS. Fabrication of magnesium-based metallic scaffolds for bone tissue engineering. Mater Technol. 2017;33(2):173–82. https://doi.org/10.1080/10667857.2017.1404278.

    Article  CAS  Google Scholar 

  237. Denry I, Kelly JR. State of the art of zirconia for dental applications. Dent Mater. 2008;24:299–308.

    Article  PubMed  CAS  Google Scholar 

  238. Al-Amleh, Lyons K, Swain M. Clinical trials in zirconia: a systematic review. J Oral Rehabil. 2010;37:641–52.

    PubMed  CAS  Google Scholar 

  239. Hulbert SF. The use of alumina and zirconia in surgical implants. In: Hench LL, Wilson J, editors. An Introduction to bioceramics. Singapore: World Scientific; 1993. p. 25–40.

    Chapter  Google Scholar 

  240. Padovan LEM, Ribero Junior MA, Sartori EM, Caludio M. Bone healing in titanium and zirconia implants surface: a pilot study on the rabbit tibia. RSBO. 2013;10(2):110–5.

    Google Scholar 

  241. Ham AW, Harris WR. Repair and transplantation of bone. Biochem PhysiolBone. 2012;3:337.

    Google Scholar 

  242. Somaiya R, Kaur G. Future of bone repair. Bone Tissue Regen Insight. 2015;6:107. https://doi.org/10.4137/BTRi.s12333.

    Article  Google Scholar 

  243. Bohner B. Resorbable biomaterials as bone graft substitutes. Mat Today. 2009;13(1):24–30. https://doi.org/10.1016/S1369-7021(10)70014-6.

    Article  Google Scholar 

  244. Lee KY, Park M, Kim HM, Lim YJ, Chun HJ, Kim H, et al. Ceramic bioactivity: progresses, challenges and perspectives. Biomed Mater. 2006;1:R31–7.

    Article  PubMed  CAS  Google Scholar 

  245. Fernandez-Yaguea MA, Abba SA, McNamarab L, Zeugolisa D, Manus AP, Biggs MJ. Biomimetic approaches in bone tissue engineering: Integrating biological and physicomechanical strategies. Adv Drug Del Rev. 2015;84:1–19.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Biological Sciences and the Center for Biomedical Engineering, Louisiana Tech University, Ruston, LA, USA

    David K. Mills

Authors
  1. David K. Mills
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David K. Mills .

Editor information

Editors and Affiliations

  1. Department of Orthopedics School of Medicine, West Virginia University, Morgantown, West Virginia, USA

    Bingyun Li

  2. Department of Chemical Engineering, Northeastern University, Boston, Massachusetts, USA

    Thomas Webster

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Mills, D.K. (2018). The Role of Polymer Additives in Enhancing the Response of Calcium Phosphate Cement. In: Li, B., Webster, T. (eds) Orthopedic Biomaterials . Springer, Cham. https://doi.org/10.1007/978-3-319-89542-0_14

Download citation

Publish with us

Policies and ethics

Search

Navigation