Osteoinductive and Osteoconductive Biomaterials

  • Shreya Agrawal
  • Rohit SrivastavaEmail author


With combinatorial approaches getting stronger to design materials with better functionalities and compatibility for restoring bone tissue, it is becoming important to understand the progress and evolution of existing and newly designed materials. For being clinically usable, they should have features that address the biomechanical, biochemical, and medical requirements.

Their various characteristics determine the cascade of events that take place at the site of bone healing. They should be selected based on the specific purpose with maximum benefit to the patient in long run. The current efforts in this domain are to render the orthopedic procedures minimally invasive and maximally effective.

This chapter encompasses the journey of classes of biomaterials used for their osteoinductive and osteoconductive properties and discusses the challenges for bringing them closer to fulfil the requisites.


Bone Osteoblasts Osteogenesis Composites Stem cells Apatite Biomimicry Implant Bioactivity Scaffold 


  1. 1.
    Laurencin CT, Khan Y, Kofron M et al (2006) THE ABJS NICOLAS ANDRY AWARD: tissue engineering of bone and ligament. Clin Orthop Relat Res. 447:221–236. Scholar
  2. 2.
    El-Ghannam A (2005) Bone reconstruction: from bioceramics to tissue engineering. Expert Rev Med Devices. 2(1):87–101. Scholar
  3. 3.
    Ozdemir T, Higgins AM, Brown JL (2013) Osteoinductive biomaterial geometries for bone regenerative engineering. Curr Pharm Des 19(19):3446–3455. Accessed 11 Apr 2019CrossRefGoogle Scholar
  4. 4.
    Urist MR (1965) Bone: formation by autoinduction. Science (80- ) 150(3698):893 LP–893899. Scholar
  5. 5.
    Wilson-Hench J (1987) Osteoinduction. Prog Biomed Eng 4:29Google Scholar
  6. 6.
    Miron RJ, Zhang YF (2012) Osteoinduction: a review of old concepts with new standrads. J Dent Res. 91(8):736–744. Scholar
  7. 7.
    Habibovic P, de Groot K (2007) Osteoinductive biomaterials—properties and relevance in bone repair. J Tissue Eng Regen Med. 1(1):25–32. Scholar
  8. 8.
    Ripamonti U. The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral. 1991. Accessed 27 Feb 2019.CrossRefGoogle Scholar
  9. 9.
    Ripamonti U (1996) Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. Biomaterials. 17(1):31–35. Scholar
  10. 10.
    Yuan H, de Bruijn JD, Zhang X, van Blitterswijk CA, de Groot K (2001) Use of an osteoinductive biomaterial as a bone morphogenetic protein carrier. J Mater Sci Mater Med. 12(9):761–766. Scholar
  11. 11.
    Reddi AH (1981) Cell biology and biochemistry of endochondral bone development. Coll Relat Res. 1(2):209–226. Scholar
  12. 12.
    Yuan H, van den Doel M, Li S, van Blitterswijk CA, de Groot K, de Bruijn JD (2002) A comparison of the osteoinductive potential of two calcium phosphate ceramics implanted intramuscularly in goats. J Mater Sci Mater Med. 13(12):1271–1275. Scholar
  13. 13.
    Ripamonti U (1991) The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral. J Bone Joint Surg Am. 73(5):692–703. Accessed 26 Feb 2019CrossRefGoogle Scholar
  14. 14.
    Ohgushi H, Goldberg VM, Caplan AI (1989) Heterotopic osteogenesis in porous ceramics induced by marrow cells. J Orthop Res. 7(4):568–578. Scholar
  15. 15.
    Goshima J, Goldberg VM, Caplan AI (1991) The osteogenic potential of culture-expanded rat marrow mesenchymal cells assayed in vivo in calcium phosphate ceramic blocks. Clin Orthop Relat Res. 262:298–311. Accessed 27 Feb 2019Google Scholar
  16. 16.
    Klein C, de Groot K, Chen W, Li Y, Zhang X (1994) Osseous substance formation induced in porous calcium phosphate ceramics in soft tissues. Biomaterials. 15(1):31–34. Scholar
  17. 17.
    Yang Z, Yuan H, Tong W, Zou P, Chen W, Zhang X (1996) Osteogenesis in extraskeletally implanted porous calcium phosphate ceramics: variability among different kinds of animals. Biomaterials. 17(22):2131–2137. Accessed 27 Feb 2019CrossRefGoogle Scholar
  18. 18.
    Hari RA (1992) Regulation of cartilage and bone differentiation by bone morphogenetic proteins. Curr Opin Cell Biol. 4(5):850–855. Scholar
  19. 19.
    Wozney JM (1992) The bone morphogenetic protein family and osteogenesis. Mol Reprod Dev. 32(2):160–167. Scholar
  20. 20.
    Liu Y, de Groot K, Hunziker E (2005) BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model. Bone. 36(5):745–757. Scholar
  21. 21.
    Barradas AMC, Yuan H, Clemens A van B, Habibovic P (2011) Osteoinductive biomaterials: current knowledge of properties, experimental models and biological mechanisms. Eur Cells Mater. 21:407–429. Scholar
  22. 22.
    Chocholata P, Kulda V, Babuska V, Chocholata P, Kulda V, Babuska V (2019) Fabrication of scaffolds for bone-tissue regeneration. Materials (Basel). 12(4):568. Scholar
  23. 23.
    Yazdimamaghani M, Razavi M, Vashaee D, Moharamzadeh K, Boccaccini AR, Tayebi L (2017) Porous magnesium-based scaffolds for tissue engineering. Mater Sci Eng C. 71:1253–1266. Scholar
  24. 24.
    Navarro M, Michiardi A, Castaño O, Planell JA (2008) Biomaterials in orthopaedics. J R Soc Interface. 5(27):1137–1158. Scholar
  25. 25.
    Kamrani S, Fleck C (2019) Biodegradable magnesium alloys as temporary orthopaedic implants: a review. BioMetals. 32(2):185–193. Scholar
  26. 26.
    Lee J-W, Han H-S, Han K-J et al (2016) Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy. Proc Natl Acad Sci U S A. 113(3):716–721. Scholar
  27. 27.
    Witte F, Feyerabend F, Maier P et al (2007) Biodegradable magnesium–hydroxyapatite metal matrix composites. Biomaterials. 28(13):2163–2174. Scholar
  28. 28.
    Courtenay J, Bryant M (2011) Bone ash replacement product is safer. Alum Times. 57Google Scholar
  29. 29.
    Charnley J (1960) Anchorage of the femoral head prosthesis to the shaft of the femur. J Bone Joint Surg Br. 42-B:28–30. Accessed 23 Apr 2019CrossRefGoogle Scholar
  30. 30.
    Yang K, Ren Y (2010) Nickel-free austenitic stainless steels for medical applications. Sci Technol Adv Mater. 11(1):014105. Scholar
  31. 31.
    Younesi M, Bahrololoom ME, Fooladfar H (2010) Development of wear resistant NFSS–HA novel biocomposites and study of their tribological properties for orthopaedic applications. J Mech Behav Biomed Mater. 3(2):178–188. Scholar
  32. 32.
    Younesi M, Bahrololoom ME (2010) Formulation of the wear behaviour of nickel-free stainless-steel/hydroxyapatite bio-composites by response surface methodology. Proc Inst Mech Eng Part J J Eng Tribol. 224(11):1197–1207. Scholar
  33. 33.
    Younesi M, Bahrololoom ME, Ahmadzadeh M (2010) Prediction of wear behaviors of nickel free stainless steel–hydroxyapatite bio-composites using artificial neural network. Comput Mater Sci. 47(3):645–654. Scholar
  34. 34.
    Montanaro L, Cervellati M, Campoccia D, Arciola CR (2006) Promising in vitro performances of a new nickel-free stainless steel. J Mater Sci Mater Med. 17(3):267–275. Scholar
  35. 35.
    Torricelli P, Fini M, Borsari V et al (2003) Biomaterials in orthopedic surgery: effects of a nickel-reduced stainless steel on in vitro proliferation and activation of human osteoblasts. Int J Artif Organs. 26(10):952–957. Scholar
  36. 36.
    Thomann UI, Uggowitzer PJ (2000) Wear–corrosion behavior of biocompatible austenitic stainless steels. Wear. 239(1):48–58. Scholar
  37. 37.
    Ren YB, Yang HJ, Yang K, Zhang BC (2007) In vitro biocompatibility of a new high nitrogen nickel free austenitic stainless steel. Key Eng Mater. 342-343:605–608. Scholar
  38. 38.
    Popkov AV, Gorbach EN, Kononovich NA, Popkov DA, Tverdokhlebov SI, Shesterikov EV (2017) Bioactivity and osteointegration of hydroxyapatite-coated stainless steel and titanium wires used for intramedullary osteosynthesis. Strateg Trauma Limb Reconstr. 12(2):107–113. Scholar
  39. 39.
    Das A, Shukla M (2019) Surface morphology, bioactivity, and antibacterial studies of pulsed laser deposited hydroxyapatite coatings on Stainless Steel 254 for orthopedic implant applications. Proc Inst Mech Eng Part L J Mater Des Appl. 233(2):120–127. Scholar
  40. 40.
    Sul Y-T, Johansson CB, Petronis S et al (2002) Characteristics of the surface oxides on turned and electrochemically oxidized pure titanium implants up to dielectric breakdown:: the oxide thickness, micropore configurations, surface roughness, crystal structure and chemical composition. Biomaterials. 23(2):491–501. Scholar
  41. 41.
    Raikar GN, Gregory JC, Ong JL et al (1995) Surface characterization of titanium implants. J Vac Sci Technol A Vacuum, Surfaces, Film 13(5):2633–2637. Scholar
  42. 42.
    de Jonge LT, Leeuwenburgh SCG, Wolke JGC, Jansen JA (2008) Organic–inorganic surface modifications for titanium implant surfaces. Pharm Res. 25(10):2357–2369. Scholar
  43. 43.
    Bierbaum S, Hempel U, Geißler U et al (2003) Modification of Ti6AL4V surfaces using collagen I, III, and fibronectin. II. Influence on osteoblast responses. J Biomed Mater Res Part A. 67A(2):431–438. Scholar
  44. 44.
    MacDonald DE, Markovic B, Allen M, Somasundaran P, Boskey AL (1998) Surface analysis of human plasma fibronectin adsorbed to commercially pure titanium materials. J Biomed Mater Res. 41(1):120–130.<120::AID-JBM15>3.0.CO;2-RCrossRefPubMedGoogle Scholar
  45. 45.
    Roessler S, Born R, Scharnweber D, Worch H, Sewing A, Dard M (2001) Biomimetic coatings functionalized with adhesion peptides for dental implants. J Mater Sci Mater Med. 12(10/12):871–877. Scholar
  46. 46.
    van den Beucken JJJP, Vos MRJ, Thüne PC et al (2006) Fabrication, characterization, and biological assessment of multilayered DNA-coatings for biomaterial purposes. Biomaterials. 27(5):691–701. Scholar
  47. 47.
    Ferris D, Moodie G, Dimond P, Giorani CW, Ehrlich M, Valentini R (1999) RGD-coated titanium implants stimulate increased bone formation in vivo. Biomaterials. 20(23-24):2323–2331. Scholar
  48. 48.
    Elmengaard B, Bechtold JE, Søballe K (2005) In vivo study of the effect of RGD treatment on bone ongrowth on press-fit titanium alloy implants. Biomaterials. 26(17):3521–3526. Scholar
  49. 49.
    Liu Y, Hunziker EB, Layrolle P, De Bruijn JD, De Groot K (2004) Bone morphogenetic protein 2 incorporated into biomimetic coatings retains its biological activity. Tissue Eng. 10(1-2):101–108. Scholar
  50. 50.
    Schmidmaier G, Wildemann B, Cromme F, Kandziora F, Haas NP, Raschke M (2002) Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: a biomechanical and histological study in rats. Bone. 30(6):816–822. Scholar
  51. 51.
    van den Beucken JJJP, Walboomers XF, Boerman OC et al (2006) Functionalization of multilayered DNA-coatings with bone morphogenetic protein 2. J Control Release 113(1):63–72. Scholar
  52. 52.
    van den Beucken JJJP, Walboomers XF, Leeuwenburgh SCG et al (2007) Multilayered DNA coatings: in vitro bioactivity studies and effects on osteoblast-like cell behavior. Acta Biomater. 3(4):587–596. Scholar
  53. 53.
    De Jonge LT, Leeuwenburgh SCG, van de Beucken J, Wolke JGC, Jansen JA (2008) Electrosprayed enzyme coatings as bio-inspired alternatives to conventional bioceramic coatings for orthopedic and oral implants. Adv Funct Mater 19:755–762CrossRefGoogle Scholar
  54. 54.
    Xia Z, Yu X, Wei M (2012) Biomimetic collagen/apatite coating formation on Ti6Al4V substrates. J Biomed Mater Res Part B Appl Biomater. 100B(3):871–881. Scholar
  55. 55.
    Nishida M, Nakaji-Hirabayashi T, Kitano H, Saruwatari Y, Matsuoka K (2017) Titanium alloy modified with anti-biofouling zwitterionic polymer to facilitate formation of bio-mineral layer. Colloids Surfaces B Biointerfaces. 152:302–310. Scholar
  56. 56.
    Yu P, Zhu X, Wang X et al (2016) Periodic nanoneedle and buffer zones constructed on a titanium surface promote osteogenic differentiation and bone calcification in vivo. Adv Healthc Mater. 5(3):364–372. Scholar
  57. 57.
    George N, Nair AB (2018) Porous tantalum: a new biomaterial in orthopedic surgery. Fundam Biomater Met:243–268.
  58. 58.
    Edelmann AR, Patel D, Allen RK, Gibson CJ, Best AM, Bencharit S (2019) Retrospective analysis of porous tantalum trabecular metal–enhanced titanium dental implants. J Prosthet Dent. 121(3):404–410. Scholar
  59. 59.
    Bencharit S, Byrd WC, Altarawneh S et al (2014) Development and applications of porous tantalum trabecular metal-enhanced titanium dental implants. Clin Implant Dent Relat Res. 16(6):817–826. Scholar
  60. 60.
    Liu Y, Bao C, Wismeijer D, Wu G (2015) The physicochemical/biological properties of porous tantalum and the potential surface modification techniques to improve its clinical application in dental implantology. Mater Sci Eng C. 49:323–329. Scholar
  61. 61.
    Lu M, Xu S, Lei Z-X et al (2019) Application of a novel porous tantalum implant in rabbit anterior lumbar spine fusion model. Chin Med J (Engl). 132(1):51–62. Scholar
  62. 62.
    Sagomonyants KB, Hakim-Zargar M, Jhaveri A, Aronow MS, Gronowicz G (2011) Porous tantalum stimulates the proliferation and osteogenesis of osteoblasts from elderly female patients. J Orthop Res. 29(4):609–616. Scholar
  63. 63.
    Lee JW, Wen HB, Gubbi P, Romanos GE (2018) New bone formation and trabecular bone microarchitecture of highly porous tantalum compared to titanium implant threads: a pilot canine study. Clin Oral Implants Res. 29(2):164–174. Scholar
  64. 64.
    Buehler WJ, Wang FE (1968) A summary of recent research on the nitinol alloys and their potential application in ocean engineering. Ocean Eng. 1(1):105–120. Scholar
  65. 65.
    Chu Y, Dai KR, Zhu M, Mi XJ (2000) Medical application of NiTi shape memory alloy in China. Mater Sci Forum. 327-328:55–62. Scholar
  66. 66.
    Duerig TW, Pelton AR, Stöckel D (1996) The utility of superelasticity in medicine. Biomed Mater Eng. 6(4):255–266. Scholar
  67. 67.
    Vallet-Regí M, Salinas AJ (2019) Ceramics as bone repair materials. Bone Repair Biomater:141–178.
  68. 68.
    Arcos D, Izquierdo-Barba I, Vallet-Regí M (2009) Promising trends of bioceramics in the biomaterials field. J Mater Sci Mater Med. 20(2):447–455. Scholar
  69. 69.
    Yoshikawa H, Myoui A (2005) Bone tissue engineering with porous hydroxyapatite ceramics. J Artif Organs. 8(3):131–136. Scholar
  70. 70.
    Rey C (1990) Calcium phosphate biomaterials and bone mineral. Differences in composition, structures and properties. Biomaterials. 11:13–15. Scholar
  71. 71.
    Ramselaar MMA, Driessens FCM, Kalk W, De Wijn JR, Van Mullem PJ (1991) Biodegradation of four calcium phosphate ceramics;in vivo rates and tissue interactions. J Mater Sci Mater Med. 2(2):63–70. Scholar
  72. 72.
    Rapacz-Kmita A, Ślósarczyk A, Paszkiewicz Z (2005) FTIR and XRD investigations on the thermal stability of hydroxyapatite during hot pressing and pressureless sintering processes. J Mol Struct. 744-747:653–656. Scholar
  73. 73.
    Bohner M, Lemaitre J (2009) Can bioactivity be tested in vitro with SBF solution? Biomaterials. 30(12):2175–2179. Scholar
  74. 74.
    Samavedi S, Whittington AR, Goldstein AS (2013) Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater. 9(9):8037–8045. Scholar
  75. 75.
    Ogata K, Imazato S, Ehara A et al (2005) Comparison of osteoblast responses to hydroxyapatite and hydroxyapatite/soluble calcium phosphate composites. J Biomed Mater Res Part A. 72A(2):127–135. Scholar
  76. 76.
    Douglas T, Pamula E, Hauk D et al (2009) Porous polymer/hydroxyapatite scaffolds: characterization and biocompatibility investigations. J Mater Sci Mater Med. 20(9):1909–1915. Scholar
  77. 77.
    Guo H, Su J, Wei J, Kong H, Liu C (2009) Biocompatibility and osteogenicity of degradable Ca-deficient hydroxyapatite scaffolds from calcium phosphate cement for bone tissue engineering. Acta Biomater. 5(1):268–278. Scholar
  78. 78.
    Capilla MV, Olid MNR, Gaya MVO, Botella CR, Romera CZ (2007) Cylindrical dental implants with hydroxyapatite- and titanium plasma spray–coated surfaces: 5-year results. J Oral Implantol 33(2):59–68.[59:CDIWHA]2.0.CO;2CrossRefGoogle Scholar
  79. 79.
    Zhou W, Liu Z, Xu S, Hao P, Xu F, Sun A (2011) Long-term survivability of hydroxyapatite-coated implants: a meta-analysis. Oral Surg. 4(1):2–7. Scholar
  80. 80.
    Zhou M, Geng Y, Li S et al (2019) Nanocrystalline hydroxyapatite-based scaffold adsorbs and gives sustained release of osteoinductive growth factor and facilitates bone regeneration in mice ectopic model. J Nanomater. 2019:1–10. Scholar
  81. 81.
    Ramires PA, Wennerberg A, Johansson CB, Cosentino F, Tundo S, Milella E (2003) Biological behavior of sol-gel coated dental implants. J Mater Sci Mater Med. 14(6):539–545. Scholar
  82. 82.
    Albrektsson T (1998) Hydroxyapatite-coated implants: a case against their use. J Oral Maxillofac Surg. 56(11):1312–1326. Scholar
  83. 83.
    de Oliveira PT, Zalzal SF, Beloti MM, Rosa AL, Nanci A (2007) Enhancement ofin vitro osteogenesis on titanium by chemically produced nanotopography. J Biomed Mater Res Part A. 80A(3):554–564. Scholar
  84. 84.
    Göransson A, Arvidsson A, Currie F et al (2009) An in vitro comparison of possibly bioactive titanium implant surfaces. J Biomed Mater Res Part A. 88A(4):1037–1047. Scholar
  85. 85.
    Hwang NS, Varghese S, Lee HJ, Zhang Z, Elisseeff J (2013) Biomaterials directed in vivo osteogenic differentiation of mesenchymal cells derived from human embryonic stem cells. Tissue Eng Part A. 19(15-16):1723–1732. Scholar
  86. 86.
    Dhivya S, Saravanan S, Sastry TP, Selvamurugan N (2015) Nanohydroxyapatite-reinforced chitosan composite hydrogel for bone tissue repair in vitro and in vivo. J Nanobiotechnology. 13(1):40. Scholar
  87. 87.
    Dickens B, Schroeder LW, Brown WE (1974) Crystallographic studies of the role of Mg as a stabilizing impurity in β-Ca3(PO4)2. The crystal structure of pure β-Ca3(PO4)2. J Solid State Chem. 10(3):232–248. Scholar
  88. 88.
    Mathew M, Schroeder LW, Dickens B, Brown WE (1977) The crystal structure of α-Ca3(PO4)2. Acta Crystallogr Sect B Struct Crystallogr Cryst Chem. 33(5):1325–1333. Scholar
  89. 89.
    Horch H-H, Sader R, Pautke C, Neff A, Deppe H, Kolk A (2006) Synthetic, pure-phase beta-tricalcium phosphate ceramic granules (Cerasorb®) for bone regeneration in the reconstructive surgery of the jaws. Int J Oral Maxillofac Surg. 35(8):708–713. Scholar
  90. 90.
    Yamada S, Heymann D, Bouler J-M, Daculsi G (1997) Osteoclastic resorption of calcium phosphate ceramics with different hydroxyapatite/β-tricalcium phosphate ratios. Biomaterials. 18(15):1037–1041. Scholar
  91. 91.
    Yao C-H, Liu B-S, Hsu S-H, Chen Y-S, Tsai C-C (2004) Biocompatibility and biodegradation of a bone composite containing tricalcium phosphate and genipin crosslinked gelatin. J Biomed Mater Res. 69A(4):709–717. Scholar
  92. 92.
    Liu H, Cai Q, Lian P et al (2010) β-tricalcium phosphate nanoparticles adhered carbon nanofibrous membrane for human osteoblasts cell culture. Mater Lett. 64(6):725–728. Scholar
  93. 93.
    Kamitakahara M, Ohtsuki C, Miyazaki T (2008) Review paper: behavior of ceramic biomaterials derived from tricalcium phosphate in physiological condition. J Biomater Appl. 23(3):197–212. Scholar
  94. 94.
    Bi L, Cheng W, Fan H, Pei G (2010) Reconstruction of goat tibial defects using an injectable tricalcium phosphate/chitosan in combination with autologous platelet-rich plasma. Biomaterials. 31(12):3201–3211. Scholar
  95. 95.
    Ellinger RF, Nery EB, Lynch KL (1986) Histological assessment of periodontal osseous defects following implantation of hydroxyapatite and biphasic calcium phosphate ceramics: a case report. Int J Periodontics Restorative Dent. 6(3):22–33. Accessed 28 Apr 2019PubMedGoogle Scholar
  96. 96.
    Daculsi G (1998) Biphasic calcium phosphate concept applied to artificial bone, implant coating and injectable bone substitute. Biomaterials. 19(16):1473–1478. Scholar
  97. 97.
    Lobo SE, Livingston Arinzeh T, Lobo SE, Livingston AT (2010) Biphasic calcium phosphate ceramics for bone regeneration and tissue engineering applications. Materials (Basel). 3(2):815–826. Scholar
  98. 98.
    Dorozhkin SV (2012) Biphasic, triphasic and multiphasic calcium orthophosphates. Acta Biomater. 8(3):963–977. Scholar
  99. 99.
    Arinzeh TL, Tran T, Mcalary J, Daculsi G (2005) A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation. Biomaterials. 26(17):3631–3638. Scholar
  100. 100.
    Amirian J, Linh NTB, Min YK, Lee B-T (2015) Bone formation of a porous Gelatin-Pectin-biphasic calcium phosphate composite in presence of BMP-2 and VEGF. Int J Biol Macromol. 76:10–24. Scholar
  101. 101.
    Ramay HR, Zhang M (2004) Biphasic calcium phosphate nanocomposite porous scaffolds for load-bearing bone tissue engineering. Biomaterials. 25(21):5171–5180. Scholar
  102. 102.
    Scotchford CA, Vickers M, Yousuf Ali S (1995) The isolation and characterization of magnesium whitlockite crystals from human articular cartilage. Osteoarthr Cartil. 3(2):79–94. Scholar
  103. 103.
    Elliott JC (1994) Structure and chemistry of the apatites and other calcium orthophosphates. Elsevier, Amsterdam. Accessed 26 Jul 2019Google Scholar
  104. 104.
    Jang HL, Lee HK, Jin K, Ahn H-Y, Lee H-E, Nam KT (2015) Phase transformation from hydroxyapatite to the secondary bone mineral, whitlockite. J Mater Chem B. 3(7):1342–1349. Scholar
  105. 105.
    Jang HL, Jin K, Lee J et al (2014) Revisiting whitlockite, the second most abundant biomineral in bone: nanocrystal synthesis in physiologically relevant conditions and biocompatibility evaluation. ACS Nano. 8(1):634–641. Scholar
  106. 106.
    Kim HD, Jang HL, Ahn H-Y et al (2017) Biomimetic whitlockite inorganic nanoparticles-mediated in situ remodeling and rapid bone regeneration. Biomaterials. 112:31–43. Scholar
  107. 107.
    Jang HL, Bin ZG, Park J et al (2016) In vitro and in vivo evaluation of whitlockite biocompatibility: comparative study with hydroxyapatite and β -tricalcium phosphate. Adv Healthc Mater. 5(1):128–136. Scholar
  108. 108.
    Cheng PT, Grabher JJ, LeGeros RZ (1988) Effects of magnesium on calcium phosphate formation. Magnesium. 7(3):123–132. Accessed 29 Apr 2019PubMedGoogle Scholar
  109. 109.
    Silver IA, Murrills RJ, Etherington DJ (1988) Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts. Exp Cell Res. 175(2):266–276. Scholar
  110. 110.
    Teitelbaum SL (2000) Bone resorption by osteoclasts. Science. 289(5484):1504–1508. Scholar
  111. 111.
    Kim H-K, Han H-S, Lee K-S et al (2017) Comprehensive study on the roles of released ions from biodegradable Mg-5 wt% Ca-1 wt% Zn alloy in bone regeneration. J Tissue Eng Regen Med. 11(10):2710–2724. Scholar
  112. 112.
    Zapanta Le Geros R (1974) Variations in the crystalline components of human dental calculus: i. crystallographic and spectroscopic methods of analysis. J Dent Res. 53(1):45–50. Scholar
  113. 113.
    Barrère F, van Blitterswijk CA, de Groot K (2006) Bone regeneration: molecular and cellular interactions with calcium phosphate ceramics. Int J Nanomedicine. 1(3):317–332. Accessed 29 Apr 2019PubMedPubMedCentralGoogle Scholar
  114. 114.
    Bodier-Houllé P, Steuer P, Voegel J-C, Cuisinier FJG (1998) First experimental evidence for human dentine crystal formation involving conversion of octacalcium phosphate to hydroxyapatite. Acta Crystallogr Sect D Biol Crystallogr. 54(6):1377–1381. Scholar
  115. 115.
    Suzuki O, Imaizumi H, Kamakura S, Katagiri T (2008) Bone regeneration by synthetic octacalcium phosphate and its role in biological mineralization. Curr Med Chem. 15(3):305–313. Scholar
  116. 116.
    Barrère F, Layrolle P, van Blitterswijk CA, de Groot K (2001) Biomimetic coatings on titanium: a crystal growth study of octacalcium phosphate. J Mater Sci Mater Med. 12(6):529–534. Scholar
  117. 117.
    Socol G, Torricelli P, Bracci B et al (2004) Biocompatible nanocrystalline octacalcium phosphate thin films obtained by pulsed laser deposition. Biomaterials. 25(13):2539–2545. Scholar
  118. 118.
    Shelton RM, Liu Y, Cooper PR, Gbureck U, German MJ, Barralet JE (2006) Bone marrow cell gene expression and tissue construct assembly using octacalcium phosphate microscaffolds. Biomaterials. 27(14):2874–2881. Scholar
  119. 119.
    Kikawa T, Kashimoto O, Imaizumi H, Kokubun S, Suzuki O (2009) Intramembranous bone tissue response to biodegradable octacalcium phosphate implant. Acta Biomater. 5(5):1756–1766. Scholar
  120. 120.
    Stefanic M, Krnel K, Pribosic I, Kosmac T (2012) Rapid biomimetic deposition of octacalcium phosphate coatings on zirconia ceramics (Y-TZP) for dental implant applications. Appl Surf Sci. 258(10):4649–4656. Scholar
  121. 121.
    ter Brugge PJ, Wolke JGC, Jansen JA (2003) Effect of calcium phosphate coating composition and crystallinity on the response of osteogenic cells in vitro. Clin Oral Implants Res. 14(4):472–480. Scholar
  122. 122.
    Combes C, Rey C (2010) Amorphous calcium phosphates: synthesis, properties and uses in biomaterials. Acta Biomater. 6(9):3362–3378. Scholar
  123. 123.
    Popp JR, Laflin KE, Love BJ, Goldstein AS (2012) Fabrication and characterization of poly(lactic-co-glycolic acid) microsphere/amorphous calcium phosphate scaffolds. J Tissue Eng Regen Med. 6(1):12–20. Scholar
  124. 124.
    Cheng H, Chabok R, Guan X et al (2018) Synergistic interplay between the two major bone minerals, hydroxyapatite and whitlockite nanoparticles, for osteogenic differentiation of mesenchymal stem cells. Acta Biomater. 69:342–351. Scholar
  125. 125.
    Jeong J, Kim JH, Shim JH, Hwang NS, Heo CY (2019) Bioactive calcium phosphate materials and applications in bone regeneration. Biomater Res. 23:4. Scholar
  126. 126.
    Ishikawa K, Miyamoto Y, Tsuchiya A et al (2018) Physical and histological comparison of hydroxyapatite, carbonate apatite, and β-tricalcium phosphate bone substitutes. Materials (Basel). 11(10):1993. Scholar
  127. 127.
    Williams DF (2008) On the mechanisms of biocompatibility. Biomaterials. 29(20):2941–2953. Scholar
  128. 128.
    Bi L, Rahaman MN, Day DE et al (2013) Effect of bioactive borate glass microstructure on bone regeneration, angiogenesis, and hydroxyapatite conversion in a rat calvarial defect model. Acta Biomater. 9(8):8015–8026. Scholar
  129. 129.
    El-Rashidy AA, Roether JA, Harhaus L, Kneser U, Boccaccini AR (2017) Regenerating bone with bioactive glass scaffolds: a review of in vivo studies in bone defect models. Acta Biomater. 62:1–28. Scholar
  130. 130.
    Fu Q (2019) Bioactive glass scaffolds for bone tissue engineering. Biomed Ther Clin Appl Bioact Glas:417–442.
  131. 131.
    Moses JC, Nandi SK, Mandal BB (2018) Multifunctional cell instructive silk-bioactive glass composite reinforced scaffolds toward osteoinductive, proangiogenic, and resorbable bone grafts. Adv Healthc Mater. 7(10):1701418. Scholar
  132. 132.
    Baino F (2018) Bioactive glasses—when glass science and technology meet regenerative medicine. Ceram Int. 44(13):14953–14966. Scholar
  133. 133.
    Srinivasan S, Jayasree R, Chennazhi KP, Nair SV, Jayakumar R (2012) Biocompatible alginate/nano bioactive glass ceramic composite scaffolds for periodontal tissue regeneration. Carbohydr Polym. 87(1):274–283. Scholar
  134. 134.
    Gkioni K, Leeuwenburgh SCG, Douglas TEL, Mikos AG, Jansen JA (2010) Mineralization of hydrogels for bone regeneration. Tissue Eng Part B Rev. 16(6):577–585. Scholar
  135. 135.
    Jones JR (2013) Review of bioactive glass: from Hench to hybrids. Acta Biomater. 9(1):4457–4486. Scholar
  136. 136.
    Zhang G, Brion A, Willemin A-S et al (2017) Nacre, a natural, multi-use, and timely biomaterial for bone graft substitution. J Biomed Mater Res Part A. 105(2):662–671. Scholar
  137. 137.
    Akilal N, Lemaire F, Bercu NB et al (2019) Cowries derived aragonite as raw biomaterials for bone regenerative medicine. Mater Sci Eng C. 94:894–900. Scholar
  138. 138.
    Anderson JM, Rodriguez A, Chang DT (2008) Foreign body reaction to biomaterials. Semin Immunol. 20(2):86–100. Scholar
  139. 139.
    Anderson JM (2001) Biological responses to materials. Annu Rev Mater Res. 31:81–110. Accessed 7 Mar 2017CrossRefGoogle Scholar
  140. 140.
    Navarro M, Michiardi A, Castano OPA (2008) Biomaterials in orthopaedics. J R Soc Interface. 5:1137–1158CrossRefGoogle Scholar
  141. 141.
    Ambrosio L, De Santis R, Nicolais L (1998) Composite hydrogels as intervertebral disc prostheses. In: Science and technology of polymers and advanced materials. Springer US, Boston, MA, pp 547–555. Scholar
  142. 142.
    Hasan A, Byambaa B, Morshed M et al (2018) Advances in osteobiologic materials for bone substitutes. J Tissue Eng Regen Med. 12(6):1448–1468. Scholar
  143. 143.
    Campana V, Milano G, Pagano E et al (2014) Bone substitutes in orthopaedic surgery: from basic science to clinical practice. J Mater Sci Mater Med. 25(10):2445–2461. Scholar
  144. 144.
    Guarino V, Caputo T, Altobelli R, Ambrosio L (2015) Degradation properties and metabolic activity of alginate and chitosan polyelectrolytes for drug delivery and tissue engineering applications. AIMS Mater Sci. 2(4):497–502. Scholar
  145. 145.
    Guarino V, Causa F, Ambrosio L (2007) Bioactive scaffolds for bone and ligament tissue. Expert Rev Med Devices. 4(3):405–418. Scholar
  146. 146.
    Chiari C, Koller U, Dorotka R et al (2006) A tissue engineering approach to meniscus regeneration in a sheep model. Osteoarthr Cartil. 14(10):1056–1065. Scholar
  147. 147.
    Marijnissen WJC, van Osch GJV, Aigner J et al (2002) Alginate as a chondrocyte-delivery substance in combination with a non-woven scaffold for cartilage tissue engineering. Biomaterials. 23(6):1511–1517. Scholar
  148. 148.
    Cancedda R, Dozin B, Giannoni P, Quarto R (2003) Tissue engineering and cell therapy of cartilage and bone. Matrix Biol. 22(1):81–91. Scholar
  149. 149.
    Revell PA, Damien E, Di Silvio L, Gurav N, Longinotti C, Ambrosio L (2007) Tissue engineered intervertebral disc repair in the pig using injectable polymers. J Mater Sci Mater Med. 18(2):303–308. Scholar
  150. 150.
    Acevedo CA, Olguín Y, Briceño M et al (2019) Design of a biodegradable UV-irradiated gelatin-chitosan/nanocomposed membrane with osteogenic ability for application in bone regeneration. Mater Sci Eng C. 99:875–886. Scholar
  151. 151.
    Ou Q, Miao Y, Yang F, Lin X, Zhang L-M, Wang Y (2019) Zein/gelatin/nanohydroxyapatite nanofibrous scaffolds are biocompatible and promote osteogenic differentiation of human periodontal ligament stem cells. Biomater Sci 7(5):1973–1983. Scholar
  152. 152.
    Cao M, Zhou Y, Mao J et al (2019) Promoting osteogenic differentiation of BMSCs via mineralization of polylactide/gelatin composite fibers in cell culture medium. Mater Sci Eng C. 100:862–873. Scholar
  153. 153.
    Anada T, Pan C-C, Stahl A et al (1096) Vascularized bone-mimetic hydrogel constructs by 3D bioprinting to promote osteogenesis and angiogenesis. Int J Mol Sci. 20(5):2019. Scholar
  154. 154.
    Ingavle GC, Gionet-Gonzales M, Vorwald CE et al (2019) Injectable mineralized microsphere-loaded composite hydrogels for bone repair in a sheep bone defect model. Biomaterials. 197:119–128. Scholar
  155. 155.
    Murahashi Y, Yano F, Nakamoto H et al (2019) Multi-layered PLLA-nanosheets loaded with FGF-2 induce robust bone regeneration with controlled release in critical-sized mouse femoral defects. Acta Biomater. 85:172–179. Scholar
  156. 156.
    Lee S-H, Shin H (2007) Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Adv Drug Deliv Rev. 59(4-5):339–359. Scholar
  157. 157.
    Vinogradov SV, Bronich TK, Kabanov AV (2002) Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells. Adv Drug Deliv Rev 54(1):135–147. Scholar
  158. 158.
    Bai X, Gao M, Syed S, Zhuang J, Xu X, Zhang X-Q (2018) Bioactive hydrogels for bone regeneration. Bioact Mater. 3(4):401–417. Scholar
  159. 159.
    Heo YJ, Shibata H, Okitsu T, Kawanishi T, Takeuchi S (2011) Long-term in vivo glucose monitoring using fluorescent hydrogel fibers. Proc Natl Acad Sci. 108(33):13399–13403. Scholar
  160. 160.
    Onat B, Tuncer S, Ulusan S, Banerjee S, Erel GI (2019) Biodegradable polymer promotes osteogenic differentiation in immortalized and primary osteoblast-like cells. Biomed Mater. 14(4):045003. Scholar
  161. 161.
    Barbieri D, Yuan H, Luo X, Farè S, Grijpma DW, de Bruijn JD (2013) Influence of polymer molecular weight in osteoinductive composites for bone tissue regeneration. Acta Biomater. 9(12):9401–9413. Scholar
  162. 162.
    Ricciardi BF, Bostrom MP (2013) Bone graft substitutes: claims and credibility. Semin Arthroplasty 24(2):119–123. Scholar
  163. 163.
    Alidadi S, Oryan A, Bigham-Sadegh A, Moshiri A (2017) Comparative study on the healing potential of chitosan, polymethylmethacrylate, and demineralized bone matrix in radial bone defects of rat. Carbohydr Polym. 166:236–248. Scholar
  164. 164.
    Lai Y, Li Y, Cao H et al (2019) Osteogenic magnesium incorporated into PLGA/TCP porous scaffold by 3D printing for repairing challenging bone defect. Biomaterials. 197:207–219. Scholar
  165. 165.
    Veronesi F, Giavaresi G, Guarino V et al (2015) Bioactivity and bone healing properties of biomimetic porous composite scaffold: in vitro and in vivo studies. J Biomed Mater Res Part A. 103(9):2932–2941. Scholar
  166. 166.
    Martínez-Sanmiguel JJ, Zarate-Triviño G, Hernandez-Delgadillo R et al (2019) Anti-inflammatory and antimicrobial activity of bioactive hydroxyapatite/silver nanocomposites. J Biomater Appl 33(10):1314–1326. Scholar
  167. 167.
    Chen Y, Zheng Z, Zhou R et al (2019) Developing a strontium-releasing graphene oxide/collagen-based organic-inorganic nanobiocomposite for large bone defect regeneration via MAPK signaling pathway. ACS Appl Mater Interfaces 11(17):15986–15997. Scholar
  168. 168.
    Arnold AM, Holt BD, Daneshmandi L, Laurencin CT, Sydlik SA (2019) Phosphate graphene as an intrinsically osteoinductive scaffold for stem cell-driven bone regeneration. Proc Natl Acad Sci U S A 116(11):4855–4860. Scholar
  169. 169.
    Narimani M, Teimouri A, Shahbazarab Z (2019) Synthesis, characterization and biocompatible properties of novel silk fibroin/graphene oxide nanocomposite scaffolds for bone tissue engineering application. Polym Bull. 76(2):725–745. Scholar
  170. 170.
    Wang W, Junior JRP, Nalesso PRL et al (2019) Engineered 3D printed poly(ɛ-caprolactone)/graphene scaffolds for bone tissue engineering. Mater Sci Eng C. 100:759–770. Scholar
  171. 171.
    Purohit SD, Bhaskar R, Singh H, Yadav I, Gupta MK, Mishra NC (2019) Development of a nanocomposite scaffold of gelatin–alginate–graphene oxide for bone tissue engineering. Int J Biol Macromol. 133:592–602. Scholar
  172. 172.
    Zhang Y, Wang J, Wang J et al (2015) Preparation of porous PLA/DBM composite biomaterials and experimental research of repair rabbit radius segmental bone defect. Cell Tissue Bank. 16(4):615–622. Scholar
  173. 173.
    Carrow JK, Di Luca A, Dolatshahi-Pirouz A, Moroni L, Gaharwar AK (2019) 3D-printed bioactive scaffolds from nanosilicates and PEOT/PBT for bone tissue engineering. Regen Biomater. 6(1):29–37. Scholar
  174. 174.
    Li X, Wang L, Fan Y, Feng Q, Cui F-Z, Watari F (2013) Nanostructured scaffolds for bone tissue engineering. J Biomed Mater Res Part A. 101A(8):2424–2435. Scholar
  175. 175.
    Bettinger CJ, Langer R, Borenstein JT (2009) Engineering substrate topography at the micro- and nanoscale to control cell function. Angew Chemie Int Ed. 48(30):5406–5415. Scholar
  176. 176.
    Peng R, Yao X, Ding J (2011) Effect of cell anisotropy on differentiation of stem cells on micropatterned surfaces through the controlled single cell adhesion. Biomaterials. 32(32):8048–8057. Scholar
  177. 177.
    McMahon RE, Wang L, Skoracki R, Mathur AB (2013) Development of nanomaterials for bone repair and regeneration. J Biomed Mater Res Part B Appl Biomater. 101B(2):387–397. Scholar
  178. 178.
    Pasqui D, Torricelli P, De Cagna M, Fini M, Barbucci R (2014) Carboxymethyl cellulose-hydroxyapatite hybrid hydrogel as a composite material for bone tissue engineering applications. J Biomed Mater Res Part A. 102(5):1568–1579. Scholar
  179. 179.
    Gelinsky M, Welzel PB, Simon P, Bernhardt A, König U (2008) Porous three-dimensional scaffolds made of mineralised collagen: Preparation and properties of a biomimetic nanocomposite material for tissue engineering of bone. Chem Eng J. 137(1):84–96. Scholar
  180. 180.
    Kilian KA, Bugarija B, Lahn BT, Mrksich M (2010) Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci. 107(11):4872–4877. Scholar
  181. 181.
    Watari S, Hayashi K, Wood JA et al (2012) Modulation of osteogenic differentiation in hMSCs cells by submicron topographically-patterned ridges and grooves. Biomaterials. 33(1):128–136. Scholar
  182. 182.
    Cai K, Frant M, Bossert J, Hildebrand G, Liefeith K, Jandt KD (2006) Surface functionalized titanium thin films: zeta-potential, protein adsorption and cell proliferation. Colloids Surfaces B Biointerfaces. 50:1–8. Scholar
  183. 183.
    Palmer LC, Newcomb CJ, Kaltz SR, Spoerke ED, Stupp SI (2008) Biomimetic systems for hydroxyapatite mineralization inspired by bone and enamel. Chem Rev. 108(11):4754–4783. Scholar
  184. 184.
    Dalby MJ, Gadegaard N, Tare R et al (2007) The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater 6(12):997–1003. Scholar
  185. 185.
    Gong T, Xie J, Liao J, Zhang T, Lin S, Lin Y (2015) Nanomaterials and bone regeneration. Bone Res. 3:15029. Scholar
  186. 186.
    Vallet-Regí M, Salinas AJ (2009) Ceramics as bone repair materials. 2nd. Elsevier, Amsterdam. Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Biosciences and BioengineeringIndian Institute of Technology BombayBombayIndia

Personalised recommendations