Recent Advances of Biphasic Calcium Phosphate Bioceramics for Bone Tissue Regeneration

  • Sung Eun Kim
  • Kyeongsoon ParkEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1250)


Biphasic calcium phosphate bioceramics consist of an intimate mixture of hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) in varying ratios. Due to their biocompatibility, osteoconductivity, and safety in in vitro, in vivo, and clinical models, they have become promising bone substitute biomaterials and are recommended for use as alternatives for or as additives in bone tissue regeneration in various orthopedic and dental applications. Many studies have demonstrated the potential uses of BCP bioceramics as scaffolds for tissue engineering. Here, we highlight the recent advances in the uses of BCP bioceramics and functionalized BCPs for bone tissue regeneration.


Marked BCP Injectable BCP/polymer Osteoinductive growth factors Drug delivery Osseointegration 



This research was supported by the Bio and Medical Technology Development Program of the NRF funded by the Korean government, MSIP (NRF-2017M3A9B3063640).


  1. 1.
    Cho TJ, Gerstenfeld LC, Einhorn TA (2002) Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res 17(3):513–520PubMedGoogle Scholar
  2. 2.
    Petite H, Viateau V, Bensaid W et al (2000) Tissue-engineered bone regeneration. Nat Biotechnol 18(9):959–963PubMedGoogle Scholar
  3. 3.
    Dorozhkin SV (2010) Bioceramics of calcium orthophosphates. Biomaterials 31(7):1465–1485PubMedGoogle Scholar
  4. 4.
    Carrodeguas RG, De Aza S (2011) Alpha-Tricalcium phosphate: synthesis, properties and biomedical applications. Acta Biomater 7(10):3536–3546PubMedGoogle Scholar
  5. 5.
    Best SM, Porter AE, Thian ES et al (2008) Bioceramics: past, present and for the future. J Eur Ceram Soc 28(7):1319–1327Google Scholar
  6. 6.
    Ebrahimi M, Botelho MG, Dorozhkin SV (2017) Biphasic calcium phosphates bioceramics (HA/TCP): concept, physicochemical properties and the impact of standardization of study protocols in biomaterials research. Mater Sci Eng C Mater Biol Appl 71:1293–1312PubMedGoogle Scholar
  7. 7.
    Rezwan K, Chen QZ, Blaker JJ et al (2006) Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27(18):3413–3431PubMedGoogle Scholar
  8. 8.
    Daculsi G, LeGeros RZ, Heughebaert M et al (1990) Formation of carbonate-apatite crystals after implantation of calcium phosphate ceramics. Calcif Tissue Int 46(1):20–27PubMedGoogle Scholar
  9. 9.
    Mercier P, Bellavance F, Cholewa J et al (1996) Long-term stability of atrophic ridges reconstructed with hydroxylapatite: a prospective study. J Oral Maxillofac Surg 54(8):960–968PubMedGoogle Scholar
  10. 10.
    Fuerst M, Niggemeyer O, Lammers L et al (2009) Articular cartilage mineralization in osteoarthritis of the hip. BMC Musculoskelet Disord 10:166PubMedPubMedCentralGoogle Scholar
  11. 11.
    Fellah BH, Gauthier O, Weiss P et al (2008) Osteogenicity of biphasic calcium phosphate ceramics and bone autograft in a goat model. Biomaterials 29(9):1177–1188PubMedGoogle Scholar
  12. 12.
    Zhang Y, Xiang Q, Dong S et al (2010) Fabrication and characterization of a recombinant fibronectin/cadherin bio-inspired ceramic surface and its influence on adhesion and ossification in vitro. Acta Biomater 6(3):776–785PubMedGoogle Scholar
  13. 13.
    Roohani-Esfahani SI, Nouri-Khorasani S, Lu Z et al (2010) The influence hydroxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coated with hydroxyapatite-PCL composites. Biomaterials 31(21):5498–5509PubMedGoogle Scholar
  14. 14.
    Chen JP, Tsai MJ, Liao HT (2013) Incorporation of biphasic calcium phosphate microparticles in injectable thermoresponsive hydrogel modulates bone cell proliferation and differentiation. Colloids Surf B: Biointerfaces 110:120–129PubMedGoogle Scholar
  15. 15.
    Tang Z, Li X, Tan Y et al (2018) The material and biological characteristics of osteoinductive calcium phosphate ceramics. Regen Biomater 5(1):43–59PubMedGoogle Scholar
  16. 16.
    Caroline Victoria E, Gnanam FD (2002) Synthesis and characterization of biphasic calcium phosphate. Trends Biomater Artif Organs 16(1):12–14Google Scholar
  17. 17.
    Jensen SS, Broggini N, Hjorting-Hansen E et al (2006) Bone healing and graft resorption of autograft, anorganic bovine bone and beta-tricalcium phosphate. A histologic and histomorphometric study in the mandibles of minipigs. Clin Oral Implants Res 17(3):237–243PubMedGoogle Scholar
  18. 18.
    Lee JH, Jung UW, Kim CS et al (2008) Histologic and clinical evaluation for maxillary sinus augmentation using macroporous biphasic calcium phosphate in human. Clin Oral Implants Res 19(8):767–771PubMedGoogle Scholar
  19. 19.
    Daculsi G, LeGeros RZ, Nery E et al (1989) Transformation of biphasic calcium phosphate ceramics in vivo: ultrastructural and physicochemical characterization. J Biomed Mater Res 23(8):883–894PubMedGoogle Scholar
  20. 20.
    Radin SR, Ducheyne P (1994) Effect of bioactive ceramic composition and structure on in vitro behavior. III. Porous versus dense ceramics. J Biomed Mater Res 28(11):1303–1309PubMedGoogle Scholar
  21. 21.
    Maeno S, Niki Y, Matsumoto H et al (2005) The effect of calcium ion concentration on osteoblast viability, proliferation and differentiation in monolayer and 3D culture. Biomaterials 26(23):4847–4855PubMedGoogle Scholar
  22. 22.
    Titorencu I, Jinga V, Constantinescu E et al (2007) Proliferation, differentiation and characterization of osteoblasts from human BM mesenchymal cells. Cytotherapy 9(7):682–696PubMedGoogle Scholar
  23. 23.
    Khoshniat S, Bourgine A, Julien M et al (2011) Phosphate-dependent stimulation of MGP and OPN expression in osteoblasts via the ERK1/2 pathway is modulated by calcium. Bone 48(4):894–902PubMedGoogle Scholar
  24. 24.
    Puttini IDO, Poli PP, Maiorana C et al (2019) Evaluation of osteoconduction of biphasic calcium phosphate ceramic in the calvaria of rats: microscopic and histometric analysis. J Funct Biomater 10:7PubMedCentralGoogle Scholar
  25. 25.
    Yuan H, Fernandes H, Habibovic P et al (2010) Osteoinductive ceramics as a synthetic alternative to autologous bone grafting. Proc Natl Acad Sci U S A 107(31):13614–13619PubMedPubMedCentralGoogle Scholar
  26. 26.
    LeGeros RZ, Lin S, Rohanizadeh R et al (2003) Biphasic calcium phosphate bioceramics: preparation, properties and applications. J Mater Sci Mater Med 14(3):201–209PubMedGoogle Scholar
  27. 27.
    Artzi Z, Weinreb M, Carmeli G et al (2008) Histomorphometric assessment of bone formation in sinus augmentation utilizing a combination of autogenous and hydroxyapatite/biphasic tricalcium phosphate graft materials: at 6 and 9 months in humans. Clin Oral Implants Res 19(7):686–692PubMedGoogle Scholar
  28. 28.
    Friedmann A, Dard M, Kleber BM et al (2009) Ridge augmentation and maxillary sinus grafting with a biphasic calcium phosphate: histologic and histomorphometric observations. Clin Oral Implants Res 20(7):708–714PubMedGoogle Scholar
  29. 29.
    Rouvillain JL, Lavalle F, Pascal-Mousselard H et al (2009) Clinical, radiological and histological evaluation of biphasic calcium phosphate bioceramic wedges filling medial high tibial valgisation osteotomies. Knee 16(5):392–397PubMedGoogle Scholar
  30. 30.
    Uzeda MJ, de Brito Resende RF, Sartoretto SC et al (2017) Randomized clinical trial for the biological evaluation of two nanostructured biphasic calcium phosphate biomaterials as a bone substitute. Clin Implant Dent Relat Res 19(5):802–811PubMedGoogle Scholar
  31. 31.
    Antonov EN, Bagratashvili VN, Whitaker MJ et al (2004) Three-dimensional bioactive and biodegradable scaffolds fabricated by surface-selective laser sintering. Adv Mater 17(3):327–330PubMedPubMedCentralGoogle Scholar
  32. 32.
    Bettinger CJ, Weinberg EJ, Kulig KM et al (2005) Three-dimensional microfluidic tissue-engineering scaffolds using a flexible biodegradable polymer. Adv Mater 18(2):165–169PubMedPubMedCentralGoogle Scholar
  33. 33.
    Freiberg S, Zhu XX (2004) Polymer microspheres for controlled drug release. Int J Pharm 282(1–2):1–18PubMedGoogle Scholar
  34. 34.
    Shim KS, Kim SE, Yun YP et al (2017) Biphasic Calcium Phosphate (BCP)-immobilized porous poly (d,l-lactic-co-glycolic acid) microspheres enhance osteogenic activities of osteoblasts. Polymers 9(7):297PubMedCentralGoogle Scholar
  35. 35.
    Yan D, Duan L, Li J et al (2011) Comparative study of percutaneous vertebroplasty and kyphoplasty in the treatment of osteoporotic vertebral compression fractures. Arch Orthop Trauma Surg 131(5):645–650PubMedGoogle Scholar
  36. 36.
    Griza S, Ueki MM, Souza DH et al (2013) Thermally induced strains and total shrinkage of the polymethyl-methacrylate cement in simplified models of total hip arthroplasty. J Mech Behav Biomed Mater 18:29–36PubMedGoogle Scholar
  37. 37.
    Tamimi F, Sheikh Z, Barralet J (2012) Dicalcium phosphate cements: brushite and monetite. Acta Biomater 8(2):474–487PubMedGoogle Scholar
  38. 38.
    Bouler JM, Pilet P, Gauthier O, Verron E (2017) Biphasic calcium phosphate ceramics for bone reconstruction: a review of biological response. Acta Biomater 53:1–12PubMedGoogle Scholar
  39. 39.
    Zhang X, Kang T, Liang PY et al (2018) Biological activity of an injectable biphasic calcium phosphate/PMMA bone cement for induced osteogensis in rabbit model. Macromol Biosci 18:1700331Google Scholar
  40. 40.
    Lee GH, Makkar P, Paul K et al (2017) Incorporation of BMP-2 loaded collagen conjugated BCP granules in calcium phosphate cement based injectable bone substitutes for improved bone regeneration. Mater Sci Eng C Mater Biol Appl 77:713–724PubMedGoogle Scholar
  41. 41.
    Kim YH, Jyoti MA, Youn MH et al (2010) In vitro and in vivo evaluation of a macro porous beta-TCP granule-shaped bone substitute fabricated by the fibrous monolithic process. Biomed Mater 5(3):35007PubMedGoogle Scholar
  42. 42.
    Sarkar SK, Lee BY, Padalhin AR et al (2016) Brushite-based calcium phosphate cement with multichannel hydroxyapatite granule loading for improved bone regeneration. J Biomater Appl 30(6):823–837PubMedGoogle Scholar
  43. 43.
    Allison DD, Grande-Allen KJ (2006) Hyaluronan: a powerful tissue engineering tool. Tissue Eng 12(8):2131–2140PubMedGoogle Scholar
  44. 44.
    Price RD, Myers S, Leigh IM et al (2005) The role of hyaluronic acid in wound healing: assessment of clinical evidence. Am J Clin Dermatol 6(6):393–402PubMedGoogle Scholar
  45. 45.
    Suzuki K, Anada T, Miyazaki T et al (2014) Effect of addition of hyaluronic acids on the osteoconductivity and biodegradability of synthetic octacalcium phosphate. Acta Biomater 10(1):531–543PubMedGoogle Scholar
  46. 46.
    Chazono M, Tanaka T, Komaki H et al (2004) Bone formation and bioresorption after implantation of injectable beta-tricalcium phosphate granules-hyaluronate complex in rabbit bone defects. J Biomed Mater Res A 70(4):542–549PubMedGoogle Scholar
  47. 47.
    Taz M, Makkar P, Imran KM et al (2019) Bone regeneration of multichannel biphasic calcium phosphate granules supplemented with hyaluronic acid. Mater Sci Eng C Mater Biol Appl 99:1058–1066PubMedGoogle Scholar
  48. 48.
    Ko CL, Chen JC, Hung CC et al (2014) Biphasic products of dicalcium phosphate-rich cement with injectability and nondispersibility. Mater Sci Eng C Mater Biol Appl 39:40–46PubMedGoogle Scholar
  49. 49.
    Takagi S, Chow LC (2001) Formation of macropores in calcium phosphate cement implants. J Mater Sci Mater Med 12(2):135–139PubMedGoogle Scholar
  50. 50.
    Friess W (1998) Collagen-biomaterial for drug delivery. Eur J Pharm Biopharm 45(2):113–136PubMedGoogle Scholar
  51. 51.
    Ferreira AM, Gentile P, Chiono V et al (2012) Collagen for bone tissue regeneration. Acta Biomater 8(9):3191–3200PubMedGoogle Scholar
  52. 52.
    Ou KL, Chung RJ, Tsai FY et al (2011) Effect of collagen on the mechanical properties of hydroxyapatite coatings. J Mech Behav Biomed Mater 4(4):618–624PubMedGoogle Scholar
  53. 53.
    Hunziker EB, Enggist L, Kuffer A et al (2012) Osseointegration: the slow delivery of BMP-2 enhances osteoinductivity. Bone 51(1):98–106PubMedGoogle Scholar
  54. 54.
    Xu Y, Wu J, Wang H et al (2013) Fabrication of electrospun poly(L-lactide-co-epsilon-caprolactone)/collagen nanoyarn network as a novel, three-dimensional, macroporous, aligned scaffold for tendon tissue engineering. Tissue Eng Part C Methods 19(12):925–936PubMedPubMedCentralGoogle Scholar
  55. 55.
    Le Nihouannen D, Guehennec LL, Rouillon T et al (2006) Micro-architecture of calcium phosphate granules and fibrin glue composites for bone tissue engineering. Biomaterials 27(13):2716–2722PubMedGoogle Scholar
  56. 56.
    Heckman JD, Ehler W, Brooks BP et al (1999) Bone morphogenetic protein but not transforming growth factor-beta enhances bone formation in canine diaphyseal nonunions implanted with a biodegradable composite polymer. J Bone Joint Surg Am 81(12):1717–1729PubMedGoogle Scholar
  57. 57.
    Street J, Bao M, deGuzman L et al (2002) Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci U S A 99(15):9656–9661PubMedPubMedCentralGoogle Scholar
  58. 58.
    Wozney JM (2002) Overview of bone morphogenetic proteins. Spine 27(16 Suppl 1):S2–S8PubMedGoogle Scholar
  59. 59.
    Karageorgiou V, Meinel L, Hofmann S et al (2004) Bone morphogenetic protein-2 decorated silk fibroin films induce osteogenic differentiation of human bone marrow stromal cells. J Biomed Mater Res A 71(3):528–537PubMedGoogle Scholar
  60. 60.
    Liu Y, Enggist L, Kuffer AF et al (2007) The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration. Biomaterials 28(16):2677–2686PubMedGoogle Scholar
  61. 61.
    Jang JW, Yun JH, Lee KI et al (2012) Osteoinductive activity of biphasic calcium phosphate with different rhBMP-2 doses in rats. Oral Surg Oral Med Oral Pathol Oral Radiol 113(4):480–487PubMedGoogle Scholar
  62. 62.
    Honkanen R, Pulkkinen P, Jarvinen R et al (1996) Does lactose intolerance predispose to low bone density? A population-based study of perimenopausal Finnish women. Bone 19(1):23–28PubMedGoogle Scholar
  63. 63.
    Bedeloglu E, Ersanli S, Arisan V (2017) Vascular endothelial growth factor and biphasic calcium phosphate in the endosseous healing of femoral defects: an experimental rat study. J Dent Sci 12(1):7–13PubMedGoogle Scholar
  64. 64.
    Kanematsu A, Yamamoto S, Ozeki M et al (2004) Collagenous matrices as release carriers of exogenous growth factors. Biomaterials 25(18):4513–4520PubMedGoogle Scholar
  65. 65.
    Ma Z, Kotaki M, Inai R et al (2005) Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue Eng 11(1–2):101–109PubMedGoogle Scholar
  66. 66.
    Shim KS, Kim HJ, Kim SE et al (2018) Simple surface biofunctionalization of biphasic calcium phosphates for improving osteogenic activity and bone tissue regeneration. J Ind Eng Chem 68:220–228Google Scholar
  67. 67.
    Sukul M, Nguyen TB, Min YK et al (2015) Effect of local sustainable release of BMP2-VEGF from nano-cellulose loaded in sponge biphasic calcium phosphate on bone regeneration. Tissue Eng A 21(11–12):1822–1836Google Scholar
  68. 68.
    Patel ZS, Young S, Tabata Y et al (2008) Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone 43(5):931–940PubMedPubMedCentralGoogle Scholar
  69. 69.
    Kempen DH, Lu L, Heijink A et al (2009) Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials 30(14):2816–2825PubMedGoogle Scholar
  70. 70.
    Noiset O, Schneider YJ, Marchand-Brynaert J (1999) Fibronectin adsorption or/and covalent grafting on chemically modified PEEK film surfaces. J Biomater Sci Polym Ed 10(6):657–677PubMedGoogle Scholar
  71. 71.
    Deckers MM, Karperien M, van der Bent C et al (2000) Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation. Endocrinology 141(5):1667–1674PubMedGoogle Scholar
  72. 72.
    Midy V, Plouet J (1994) Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts. Biochem Biophys Res Commun 199(1):380–386PubMedGoogle Scholar
  73. 73.
    Frost HM (1989) The biology of fracture healing. An overview for clinicians. Part I. Clin Orthop Relat Res 248:283–293Google Scholar
  74. 74.
    Su J, Xu H, Sun J et al (2013) Dual delivery of BMP-2 and bFGF from a new nano-composite scaffold, loaded with vascular stents for large-size mandibular defect regeneration. Int J Mol Sci 14(6):12714–12728PubMedPubMedCentralGoogle Scholar
  75. 75.
    Marx RE (2004) Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 62(4):489–496PubMedGoogle Scholar
  76. 76.
    Liao HT, Marra KG, Rubin JP (2014) Application of platelet-rich plasma and platelet-rich fibrin in fat grafting: basic science and literature review. Tissue Eng B Rev 20(4):267–276Google Scholar
  77. 77.
    Feng L, Chang W, Tian B et al (2017) Bone regeneration combining platelet rich plasma with engineered bone tissue. J Biomater Tissue Eng 7:841–847Google Scholar
  78. 78.
    Liao HT, Chen JP, Lee MY (2013) Bone tissue engineering with adipose-derived stem cells in bioactive composites of laser-sintered porous polycaprolactone scaffolds and platelet-rich plasma. Materials (Basel) 6(11):4911–4929Google Scholar
  79. 79.
    Liao HT, Tsai MJ, Brahmayya M et al (2018) Bone regeneration using adipose-derived stem cells in injectable thermo-gelling hydrogel scaffold containing platelet-rich plasma and biphasic calcium phosphate. Int J Mol Sci 19:2537PubMedCentralGoogle Scholar
  80. 80.
    Ripamonti U, Parak R, Klar RM et al (2016) The synergistic induction of bone formation by the osteogenic proteins of the TGF-beta supergene family. Biomaterials 104:279–296PubMedGoogle Scholar
  81. 81.
    Ziegler J, Mayr-Wohlfart U, Kessler S et al (2002) Adsorption and release properties of growth factors from biodegradable implants. J Biomed Mater Res 59(3):422–428PubMedGoogle Scholar
  82. 82.
    Chou JWL, Decarie D, Dumont RJ et al (2001) Stability of dexamethasone in extemporaneously prepared oral suspensions. Can J Hosp Pharm 54:97–103Google Scholar
  83. 83.
    Inoue Y, Hisa I, Seino S et al (2010) Alendronate induces mineralization in mouse osteoblastic MC3T3-E1 cells: regulation of mineralization-related genes. Exp Clin Endocrinol Diabetes 118(10):719–723PubMedGoogle Scholar
  84. 84.
    von Knoch F, Jaquiery C, Kowalsky M et al (2005) Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells. Biomaterials 26(34):6941–6949Google Scholar
  85. 85.
    Wang CZ, Chen SM, Chen CH et al (2010) The effect of the local delivery of alendronate on human adipose-derived stem cell-based bone regeneration. Biomaterials 31(33):8674–8683PubMedGoogle Scholar
  86. 86.
    Porras AG, Holland SD, Gertz BJ (1999) Pharmacokinetics of alendronate. Clin Pharmacokinet 36(5):315–328PubMedGoogle Scholar
  87. 87.
    Moon HJ, Yun YP, Han CW et al (2011) Effect of heparin and alendronate coating on titanium surfaces on inhibition of osteoclast and enhancement of osteoblast function. Biochem Biophys Res Commun 413(2):194–200PubMedGoogle Scholar
  88. 88.
    Kim CW, Yun YP, Lee HJ et al (2010) In situ fabrication of alendronate-loaded calcium phosphate microspheres: controlled release for inhibition of osteoclastogenesis. J Control Release 147(1):45–53PubMedGoogle Scholar
  89. 89.
    Park KW, Yun YP, Kim SE et al (2015) The effect of alendronate loaded biphasic calcium phosphate scaffolds on bone regeneration in a rat tibial defect model. Int J Mol Sci 16:26738–26753PubMedPubMedCentralGoogle Scholar
  90. 90.
    Amjadian S, Seyedjafari E, Zeynali B et al (2016) The synergistic effect of nano-hydroxyapatite and dexamethasone in the fibrous delivery system of gelatin and poly(l-lactide) on the osteogenesis of mesenchymal stem cells. Int J Pharm 507(1–2):1–11PubMedGoogle Scholar
  91. 91.
    Chen Y, Kawazoe N, Chen G (2018) Preparation of dexamethasone-loaded biphasic calcium phosphate nanoparticles/collagen porous composite scaffolds for bone tissue engineering. Acta Biomater 67:341–353PubMedGoogle Scholar
  92. 92.
    Cornelini R, Rubini C, Fioroni M et al (2003) Transforming growth factor-beta 1 expression in the peri-implant soft tissues of healthy and failing dental implants. J Periodontol 74(4):446–450PubMedGoogle Scholar
  93. 93.
    Sadowska JM, Wei F, Guo J et al (2018) Effect of nano-structural properties of biomimetic hydroxyapatite on osteoimmunomodulation. Biomaterials 181:318–332PubMedGoogle Scholar
  94. 94.
    Santiago B, Gutierrez-Canas I, Dotor J et al (2005) Topical application of a peptide inhibitor of transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis. J Invest Dermatol 125(3):450–455PubMedGoogle Scholar
  95. 95.
    Janssens K, ten Dijke P, Janssens S et al (2005) Transforming growth factor-beta1 to the bone. Endocr Rev 26(6):743–774PubMedGoogle Scholar
  96. 96.
    Sevilla P, Cirera A, Dotor J et al (2018) In vitro cell response on CP-Ti surfaces functionalized with TGF-beta1 inhibitory peptides. J Mater Sci Mater Med 29(6):73PubMedGoogle Scholar
  97. 97.
    Filvaroff E, Erlebacher A, Ye J et al (1999) Inhibition of TGF-beta receptor signaling in osteoblasts leads to decreased bone remodeling and increased trabecular bone mass. Development 126(19):4267–4279PubMedGoogle Scholar
  98. 98.
    Shen ZJ, Kim SK, Jun DY et al (2007) Antisense targeting of TGF-beta1 augments BMP-induced upregulation of osteopontin, type I collagen and Cbfa1 in human Saos-2 cells. Exp Cell Res 313(7):1415–1425PubMedGoogle Scholar
  99. 99.
    Ezquerro IJ, Lasarte JJ, Dotor J et al (2003) A synthetic peptide from transforming growth factor beta type III receptor inhibits liver fibrogenesis in rats with carbon tetrachloride liver injury. Cytokine 22(1–2):12–20PubMedGoogle Scholar
  100. 100.
    Vicent S, Luis-Ravelo D, Anton I et al (2008) A novel lung cancer signature mediates metastatic bone colonization by a dual mechanism. Cancer Res 68(7):2275–2285PubMedGoogle Scholar
  101. 101.
    Serrati S, Margheri F, Pucci M et al (2009) TGFbeta1 antagonistic peptides inhibit TGFbeta1-dependent angiogenesis. Biochem Pharmacol 77(5):813–825PubMedGoogle Scholar
  102. 102.
    Cirera A, Manzanares MC, Sevilla P et al (2019) Biofunctionalization with a TGFβ-1 inhibitor peptide in the osseointegration of synthetic bone grafts: an in vivo study in beagle dogs. Materials 12:3168PubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of Orthopedic Surgery and Rare Diseases InstituteKorea University Medical College, Korea University Guro HospitalSeoulRepublic of Korea
  2. 2.Department of Systems BiotechnologyChung-Ang UniversityAnseong-siRepublic of Korea

Personalised recommendations