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

  • David K. MillsEmail author


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.


Additives Bone repair Calcium phosphate Functionalities Nanoparticles Natural and synthetic polymers Regeneration Tissue engineering 


  1. 1.
    Liu Y, Lim, Teoh S-H. Review: development of clinically relevant scaffolds for vascularised bone tissue engineering. Biotechnol Adv. 2013;31:688–705.PubMedCrossRefGoogle Scholar
  2. 2.
    Cortesini R. Stem cells, tissue engineering and organogenesis in transplantation. Transpl Immunol. 2005;15:81–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Amini AR, Laurencin CT, Nukavarapu SP. Bone tissue engineering: recent advances and challenges. Crit Rev Bioeng. 2012;40:363–408.Google Scholar
  4. 4.
    Cancedda R, Dozin B, Giannoni P, Quarto R. Tissue engineering and cell therapy of cartilage and bone. Matrix Biol. 2003;22:81–91.PubMedCrossRefGoogle Scholar
  5. 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. 6.
    Stevens MM. Biomaterials for bone tissue engineering. Mater Today. 2008;11(5):18–25.CrossRefGoogle Scholar
  7. 7.
    Katagiri BT, Takahashi N. Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis. 2002;8:147–59.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 9.
    Matassi F, et al. New biomaterials for bone regeneration. Clin Cases Min Bone Metab. 2011;8:21–4.Google Scholar
  10. 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. 11.
    Puppi D, Chiellini F, Piras AM, Chiellini E. Polymeric materials for bone and cartilage repair. Prog Poly Sci. 2010;35:403–40.CrossRefGoogle Scholar
  12. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 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. Scholar
  14. 14.
    Ginebra MP. Cements as bone repair materials. In: Planell JA, editor. Bone repair biomaterials. Cambridge, England: Woodhead Publishing Limited; 2009.Google Scholar
  15. 15.
    Hollinger J, Einhorn TA, Doll F, Sfeir C. Bone tissue engineering. Boca Raton, FL: CRC Press; 2004.Google Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 19.
    Dorozhkin SV, Epple M. Biological and medical significance of calcium phosphates. Angew Chem Int Ed. 2002;41:3130–46.CrossRefGoogle Scholar
  20. 20.
    Barinov S, Komlev VS. Calcium phosphate bone cements. Inorg Mater. 2011;47(13):1470–85.CrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 22.
    Dorozhkin SV. Calcium orthophosphates. J Mater Sci Mater Med. 2007;42(4):1061–95.CrossRefGoogle Scholar
  23. 23.
    LeGeros RZ, Chohayeb A, Shulman A. Apatitic calcium phosphates: possible dental restorative materials. J Dent Res. 1982;61:343.Google Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Ducheyne P, Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials. 1999;20:2287–303.PubMedCrossRefGoogle Scholar
  27. 27.
    Bohner M. Reactivity of calcium phosphate cements. J Mater Chem. 2007;17(38):3980–92.CrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 29.
    Kühn KD. Properties of bone cement. In: Breusch S, editor. The well-cemented total hip arthroplasty. Heidelberg: Springer MedizinVerlag; 2005. p. 52–9.CrossRefGoogle Scholar
  30. 30.
    Ginebra MP, Traykova T, Planell JA. Calcium phosphate cements: competitive drug carriers for the musculoskeletal system? Biomaterials. 2006;27:2171–7.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 33.
    DiMaio FR. The science of bone cement: a historical review. Orthopedics. 2002;25(12):1399–407.PubMedGoogle Scholar
  34. 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.CrossRefGoogle Scholar
  35. 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. Scholar
  36. 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. published online 20 March.CrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.CrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. 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.CrossRefGoogle Scholar
  45. 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. 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.CrossRefGoogle Scholar
  47. 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.CrossRefGoogle Scholar
  48. 48.
    Dutta PK. Chitin and chitosan for regenerative medicine. In: Springer series on polymer and composite materials. Berlin: Springer; 2015.Google Scholar
  49. 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.CrossRefGoogle Scholar
  50. 50.
    Driessens FCM, Planell J, Boltong MG, Khairoun I, Ginebra MP. Osteotransductive bone cements. J Eng Med. 1998;212(6):427–35.CrossRefGoogle Scholar
  51. 51.
    Bigi A, Bracci B, Panzavolta S. Effect of added gelatin on the properties of calcium phosphate cement. Biomaterials. 2004;25(14):2893–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Rinaudo M. Chitin and chitosan: properties and applications. Prog Poly Sci. 2006;31(7):603–32.CrossRefGoogle Scholar
  53. 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.PubMedCrossRefGoogle Scholar
  54. 54.
    Padois K, Rodriguez F. Effects of chitosan addition to self-setting bone cement. Biomed Mater Eng. 2007;17(5):309–20.PubMedGoogle Scholar
  55. 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. Scholar
  56. 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.PubMedCrossRefGoogle Scholar
  57. 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. Scholar
  58. 58.
    Janmey PA, Winer JP, Weisel JW. Fibrin gels and their clinical and bioengineering applications. J R Soc Interface. 2009;6(30):1–10.PubMedCrossRefGoogle Scholar
  59. 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.PubMedCrossRefGoogle Scholar
  60. 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. 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.CrossRefGoogle Scholar
  62. 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.PubMedCrossRefGoogle Scholar
  63. 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. Scholar
  64. 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.CrossRefGoogle Scholar
  65. 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. 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. 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. Scholar
  68. 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. 69.
    Unuma H, Matsuchima Y. Preparation of calcium phosphate cement with an improved setting behavior. J Asian Ceramic Soc. 2013;1(1):26–9.CrossRefGoogle Scholar
  70. 70.
    Azami M, Mohamma RE, Fathollah M. Gelatin/hydroxyapatite nanocomposite scaffolds for bone repair. Plast Res. 2010. doi:
  71. 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.CrossRefGoogle Scholar
  72. 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. Scholar
  73. 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.CrossRefGoogle Scholar
  74. 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. Scholar
  75. 75.
    Sionkowska A, Skrzyński S, Śmiechowski K, Kołodziejczak A. The review of versatile application of collagen. Polym Adv Technol. 2017;28:4–9. Scholar
  76. 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.PubMedCrossRefGoogle Scholar
  77. 77.
    Dong C, Lv Y. Application of collagen scaffold in tissue engineering: recent advances and new perspectives. Polymers. 2016;8(2):42. Scholar
  78. 78.
    Ferreira AM, Gentile P, Chono V, Ciardelli G. Collagen for bone tissue regeneration. Acta Biomat. 2012;8(9):3191–200.CrossRefGoogle Scholar
  79. 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. Scholar
  80. 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. Scholar
  81. 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. Scholar
  82. 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.
  83. 83.
    Maas M, Guo P, Keeney M, et al. Preparation of mineralized nanofibers: collagen fibrils containing calcium phosphate. Nano Lett. 2011;11:1383–8.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 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.PubMedCrossRefGoogle Scholar
  85. 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.CrossRefGoogle Scholar
  86. 86.
    Carey LE, Xu HH, Simon CG, et al. Premixed rapid-setting calcium phosphate composites for bone repair. Biomaterials. 2005;26(24):5002–14.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Takagi S, Chow LC, Hirayama S, et al. Premixed calcium–phosphate cement pastes. J Biomed Mater Res B. 2003;67(2):689–96.CrossRefGoogle Scholar
  88. 88.
    Tozzi G, Mori A, Oliveira A, Roldo M. Composite hydrogels for bone regeneration. Materials. 2016;9:267. Scholar
  89. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Planell JA, Best SM, Lacroix D, Merolli A. Bone repair biomaterials. Amsterdam: CRC Press, Elsevier; 2009.CrossRefGoogle Scholar
  91. 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. Scholar
  92. 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. Scholar
  93. 93.
    Kroeze RJ, Helder MN, Govaert LE, Smit TH. Biodegradable polymers in bone tissue engineering. Mater. 2009;2:833–56. Scholar
  94. 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. Scholar
  95. 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. Scholar
  96. 96.
    Geffers M, Groll J, Gbureck U. Reinforcement strategies for load-bearing calcium phosphate biocements. Materials. 2015;8:2700–17. Scholar
  97. 97.
    Sun J, Tan H. Alginate-based biomaterials for regenerative medicine applications. Materials. 2013;6:1285–308.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Venkstesan J, Nithya R, Kim SK. Role of alginate in bone tissue engineering. Adv Food Nutr Res. 2014;73:45–57.CrossRefGoogle Scholar
  100. 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.PubMedCrossRefGoogle Scholar
  101. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 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.Google Scholar
  103. 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.CrossRefGoogle Scholar
  104. 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. Scholar
  105. 105.
    Karnik S, Mills DK. Nanoenhanced hydrogel system with sustained release capabilities. J Biomed Mater Res A. 2015;103(7):2416–26.PubMedCrossRefGoogle Scholar
  106. 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.CrossRefGoogle Scholar
  107. 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.CrossRefGoogle Scholar
  108. 108.
    Muzzarelli RAA. Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone. Carbohydr Polym. 2009;76:167182.CrossRefGoogle Scholar
  109. 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.PubMedCrossRefGoogle Scholar
  110. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 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. 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.PubMedCrossRefGoogle Scholar
  114. 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.PubMedCrossRefGoogle Scholar
  115. 115.
    Wnek GE, Bowlin GL. Encyclopedia of biomaterials and biomedical engineering. New York: Marcel Dekker; 2004.Google Scholar
  116. 116.
    Bleek K, Taubert A. New developments in polymer-controlled, bioinspired calcium phosphate mineralization from aqueous solution. Acta Biomater. 2013;9(5):6283–321.PubMedCrossRefGoogle Scholar
  117. 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. 118.
    Rebelo R, Fernandesa M, Fangueiroa R. Biopolymers in medical implants: a brief review. Process Eng. 2017;200:236–43.Google Scholar
  119. 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:
  120. 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.CrossRefGoogle Scholar
  121. 121.
    Verma D, Katti K, Mohanty B. Mechanical properties of biomimetic composites for bone tissue engineering. MRS Proc. 2004;844:Y6.2. Scholar
  122. 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.CrossRefGoogle Scholar
  123. 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.CrossRefGoogle Scholar
  124. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  125. 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. Scholar
  126. 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. Epub 2013 Aug 16.CrossRefPubMedGoogle Scholar
  127. 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.PubMedCrossRefGoogle Scholar
  128. 128.
  129. 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. Scholar
  130. 130.
    Adeosun SO, Lawal GI, Gbenebor P. Characteristics of biodegradable implants. J Min Mater Charact Eng. 2014;2:88–106.Google Scholar
  131. 131.
    Rajendran T, Venugopalan S. Role of polylactic acid in bone regeneration–a systematic review. J Pharm Sci Res. 2015;7(11):960–6.Google Scholar
  132. 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.PubMedCrossRefGoogle Scholar
  133. 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. Scholar
  134. 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.PubMedCrossRefGoogle Scholar
  135. 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.PubMedCrossRefGoogle Scholar
  136. 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.CrossRefGoogle Scholar
  137. 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. 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. Scholar
  139. 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. Scholar
  140. 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. Scholar
  141. 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. Scholar
  142. 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. Scholar
  143. 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. Scholar
  144. 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.CrossRefGoogle Scholar
  145. 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.PubMedCrossRefGoogle Scholar
  146. 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. Scholar
  147. 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.CrossRefGoogle Scholar
  148. 148.
    Venkatesan J, Pallela R, Kim SK. Applications of carbon nanomaterials in bone tissue engineering. J Biomed Nanotechnol. 2014;10:3105–23.PubMedCrossRefGoogle Scholar
  149. 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.CrossRefGoogle Scholar
  150. 150.
    Leporatti S. Halloysite clay nanotubes as nano-bazookas for drug delivery. Polym Int. 2017;66:1111–8. Scholar
  151. 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.CrossRefGoogle Scholar
  152. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  153. 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.CrossRefGoogle Scholar
  154. 154.
    Naumenko EA, Guryanov ID, Yendluri R, Lvov YM, Fakhrullin RF. Clay nanotube-biopolymer composite scaffolds for tissue engineering. Nanoscale. 2016;8:7257–71.PubMedCrossRefPubMedCentralGoogle Scholar
  155. 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.CrossRefGoogle Scholar
  156. 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.CrossRefGoogle Scholar
  157. 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. 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. 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. 160.
    Tomas H, Alves CS, Rodrigues J. Laponite®: a key nanoplatform for biomedical applications?. Nanomed Nanotech Biol Med. 2017, in press.Google Scholar
  161. 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.CrossRefGoogle Scholar
  162. 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. Scholar
  163. 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. Scholar
  164. 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.2016.01.00636Google Scholar
  165. 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.CrossRefGoogle Scholar
  166. 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.CrossRefGoogle Scholar
  167. 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. Scholar
  168. 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. Epub 2015 Jul 26.CrossRefPubMedPubMedCentralGoogle Scholar
  169. 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.CrossRefGoogle Scholar
  170. 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.CrossRefGoogle Scholar
  171. 171.
    Kwon SY, Cho EH, Kim SS. Preparation and characterization of bone cements incorporated with montmorillonite. J Biomed Mater Res. 2007;83B:276–84. Scholar
  172. 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.CrossRefGoogle Scholar
  173. 173.
    Hamzah AA, Selvarajan RS, Majlis BY. Graphene for biomedical applications: a review. Sains Malaysiana. 2017;46(7):1125–39. Scholar
  174. 174.
    Pattnaik S, Swain K, Linc Z. Graphene and graphene-based nanocomposites: biomedical applications and biosafety. J Mater Chem B. 2016;4:7813–31.CrossRefGoogle Scholar
  175. 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. 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.PubMedCrossRefGoogle Scholar
  177. 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.CrossRefGoogle Scholar
  178. 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.PubMedCrossRefGoogle Scholar
  179. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  180. 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. 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.CrossRefGoogle Scholar
  182. 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. Scholar
  183. 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.CrossRefGoogle Scholar
  184. 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). Epub 2017 Nov 27.
  185. 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.CrossRefGoogle Scholar
  186. 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.CrossRefGoogle Scholar
  187. 187.
    Kikuchi M. Hydroxyapatite/collagen bone-like nanocomposite. Biol Pharm Bull. 2013;36(11):1666–9.PubMedCrossRefGoogle Scholar
  188. 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. Scholar
  189. 189.
    Bohner M, Baroud G. Injectability of calcium phosphate pastes. Biomaterials. 2005;26:1553–63.PubMedCrossRefGoogle Scholar
  190. 190.
    Blokhuis TJ. Formulations and delivery vehicles for bone morphogenetic proteins: latest advances and future directions. Injury. 2009;40(Suppl 3):S8–11.PubMedCrossRefGoogle Scholar
  191. 191.
    Kretlow JD, Young S, Klouda L, Wong M, Mikos AG. Injectable biomaterials for regenerating complex craniofacial tissues. Adv Mater. 2009;21:3368–93.PubMedPubMedCentralCrossRefGoogle Scholar
  192. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 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. 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.PubMedCrossRefGoogle Scholar
  195. 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.CrossRefGoogle Scholar
  196. 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.CrossRefGoogle Scholar
  197. 197.
    Yasmeen S, lo MK, Bajarcharya S, Roldo M. Injectable scaffolds for bone regeneration. Langmuir. 2014;30(43):12977–85. Scholar
  198. 198.
    Polo-Corrales L, Latorre-Esteves M, Ramirez JE. Scaffold design for bone regeneration. J Nanosci Nanotechnol. 2014;14(1):15–56.PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Devescovi V, Leonardi E, Ciapetti G, Cenni E. Growth factors in bone repair. Musculoskel Surg. 2008;92:161–8.Google Scholar
  200. 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. Scholar
  201. 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.PubMedCrossRefGoogle Scholar
  202. 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. Scholar
  203. 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. Scholar
  204. 204.
    Nicodemus GD, Bryant SJ. Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng B Rev. 2008;14(2):149–65. Scholar
  205. 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:
  206. 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.CrossRefGoogle Scholar
  207. 207.
    Bendtsen ST. Alginate hydrogels for bone tissue regeneration. 2017. Doctoral Dissertations. 1409.
  208. 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.PubMedCrossRefGoogle Scholar
  209. 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. Scholar
  210. 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. Scholar
  211. 211.
    Burdick JA, Anseth K. Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials. 2002;23(22):4513–23.CrossRefGoogle Scholar
  212. 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. 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.CrossRefGoogle Scholar
  214. 214.
    Gerhardt L-C, Boccaccini AR. Bioactive glass and glass-ceramic scaffolds for bone tissue engineering. Materials. 2010;3:3867–910. Scholar
  215. 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. Scholar
  216. 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.CrossRefGoogle Scholar
  217. 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. Scholar
  218. 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.CrossRefGoogle Scholar
  219. 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. 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. 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.CrossRefGoogle Scholar
  222. 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.CrossRefGoogle Scholar
  223. 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.PubMedCrossRefGoogle Scholar
  224. 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. Scholar
  225. 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.CrossRefGoogle Scholar
  226. 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. Scholar
  227. 227.
    Tran N, Webster TJ. Increased osteoblast functions in the presence of hydroxyapatite-coated iron oxide nanoparticles. Acta Biomater. 2011;7(3):1298–306.PubMedCrossRefGoogle Scholar
  228. 228.
    Midde S. Osteoblast functionality on bioactive TiO2 nanosubstrates. MS Thesis, Louisiana Tech University, Ruston LA. 71272.Google Scholar
  229. 229.
    Goto K, et al. Bioactive bone cements containing nano-sized titania particles for use as bone substitutes. Biomaterials. 2005;26(33):6496–505.PubMedCrossRefGoogle Scholar
  230. 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. 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.PubMedCrossRefGoogle Scholar
  232. 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.CrossRefGoogle Scholar
  233. 233.
    Ishimi Y. Nutrition and bone health. Magnesium and bone. Clin Calc. 2010, 20(5): 762–7. CliCa1005762767.Google Scholar
  234. 234.
    Weng L, Webster TJ. Nanostructured magnesium has fewer detrimental effects on osteoblast function. Int J Nanomedicine. 2013;8:1773–81. Scholar
  235. 235.
    Staiger MP, Pietak AM, Huadmai J, Dias G. Magnesium and its alloys as orthopedic biomaterials: a review. Biomaterials. 2006;27:1728–34. Scholar
  236. 236.
    Malladi L, Mahapatro A, Gomes AS. Fabrication of magnesium-based metallic scaffolds for bone tissue engineering. Mater Technol. 2017;33(2):173–82. Scholar
  237. 237.
    Denry I, Kelly JR. State of the art of zirconia for dental applications. Dent Mater. 2008;24:299–308.PubMedCrossRefGoogle Scholar
  238. 238.
    Al-Amleh, Lyons K, Swain M. Clinical trials in zirconia: a systematic review. J Oral Rehabil. 2010;37:641–52.PubMedGoogle Scholar
  239. 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.CrossRefGoogle Scholar
  240. 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. 241.
    Ham AW, Harris WR. Repair and transplantation of bone. Biochem PhysiolBone. 2012;3:337.Google Scholar
  242. 242.
    Somaiya R, Kaur G. Future of bone repair. Bone Tissue Regen Insight. 2015;6:107. Scholar
  243. 243.
    Bohner B. Resorbable biomaterials as bone graft substitutes. Mat Today. 2009;13(1):24–30. Scholar
  244. 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.PubMedCrossRefGoogle Scholar
  245. 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.CrossRefGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Biological Sciences and the Center for Biomedical EngineeringLouisiana Tech UniversityRustonUSA

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