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The effects of functionalized titanium with alendronate and bone morphogenic protein-2 for improving osteoblast activity

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

The aim of this study was to investigate the effect of functionalized titanium (Ti) with alendronate (Aln) and bone morphogenic protein-2 (BMP-2) for enhancement of osteoblast activity in vitro. Aln and/or BMP-2 were sequentially immobilized to the heparinized-Ti (Hep-Ti) surface. The compositions of pristine Ti and Hep-Ti with or without Aln and/or BMP-2 were characterized by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). Aln and/or BMP-2 onto Hep-Ti surface were released in a sustained manner. Osteoblast activities on all Ti substrates were investigated by cell proliferation assays, alkaline phosphate (ALP) activity, calcium deposition, gene expressions of osteocalcin and osteopontin. Aln/BMP-2/Hep-Ti significantly enhanced ALP activity, calcium mineral deposition, and gene expressions of osteoblast cells when compared with pristine Ti, Aln/Hep-Ti, and BMP-2/Hep-Ti. From these results, functionalized Ti substrates with alendronate and BMP-2 such as Aln/BMP-2/Hep-Ti are a promising material for the enhanced osteoblast activities in orthopedic and dental fields.

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Abbreviations

Ti:

Titanium

Aln:

Alendronate

BMP-2:

Bone morphogenic protein-2

Hep-Ti:

Heparinized-Ti

XPS:

X-ray photoelectron spectroscopy

ALP:

Alkaline phosphate

Aln/Hep-Ti:

Alendronate-immobilized Hep-Ti

BMP-2/Hep-Ti:

BMP-2-immobilized Hep-Ti

Aln/BMP-2/Hep-Ti:

Alendronate and BMP-2-immobilized Hep-Ti

Hep-DOPA:

Heparin-dopamine

References

  1. L Le Guéhennec, A Soueidan, P Layrolle, et al., Surface treatments of titanium dental implants for rapid osseointegration, Dent Mater, 23, 844 (2007).

    Article  PubMed  Google Scholar 

  2. Z Schwartz, BD Boyan, Underlying mechanisms at the bonebiomaterial interface, J Cell Biochem, 56, 340 (1994).

    Article  PubMed  CAS  Google Scholar 

  3. G Balasundaram, TJ Webster, Increased osteoblast adhesion on nanograined Ti modified with KRSR, J Biomed Mater Res A, 80, 602 (2007).

    PubMed  Google Scholar 

  4. C Chen, IS Lee, SM Zhang, et al., Biomimetic apatite formation on calcium phosphate-coated titanium in Dulbecco’s phosphate-buffered saline solution containing CaCl2 with and without fibronectin, Acta Biomater, 6, 2274 (2010).

    Article  PubMed  CAS  Google Scholar 

  5. Y Ku, CP Chung, JH Jang, The effect of the surface modification of titanium using a recombinant fragment of fibronectin and vitronectin on cell behavior, Biomaterials, 26, 5153 (2005).

    Article  PubMed  CAS  Google Scholar 

  6. K Oya, Y Tanaka, H Saito, et al., Calcification by MC3T3-E1 cells on RGD peptide immobilized on titanium through electrodeposited PEG, Biomaterials, 30, 1281 (2009).

    Article  PubMed  CAS  Google Scholar 

  7. Z Shi, KG Neoh, ET Kang, et al., Bacterial adhesion and osteoblast function on titanium with surface-grafted chitosan and immobilized RGD peptide, J Biomed Mater Res A, 86, 865 (2008).

    PubMed  Google Scholar 

  8. L Zhang, UD Hemraz, H Fenniri, et al., Tuning cell adhesion on titanium with osteogenic rosette nanotubes, J Biomed Mater Res A, 95, 550 (2010).

    PubMed  Google Scholar 

  9. R Leesungbok, SW Lee, SJ Ahn, et al., Specific temporal culturing and microgroove depth influence osteoblast differentiation of human periodontal ligament cells grown on titanium substrats, Tissue Eng Regen Med, 9, 128 (2012).

    Article  CAS  Google Scholar 

  10. OA Arosarena, D Puleo, In vitro effects of combined and sequential bone morphogenetic protein administration, Arch Facial Plast Surg, 9, 242(2007).

    Article  PubMed  Google Scholar 

  11. SD Cook, MW Wolfe, SL Salkeld, et al., Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates, J Bone Joint Surg Am, 77, 734 (1995).

    PubMed  CAS  Google Scholar 

  12. SE Kim, O Jeon, JB Lee, et al., Enhancement of ectopic bone formation by bone morphogenetic protein-2 delivery using heparin-conjugated PLGA nanoparticles with transplantation of bone marrow-derived mesenchymal stem cells, J Biomed Sci, 15, 771 (2008).

    Article  PubMed  CAS  Google Scholar 

  13. EA Wang, V Rosen, JS D’Alessandro, et al., Recombinant human bone morphogenetic protein induces bone formation, Proc Natl Acad Sci U S A, 87, 2220 (1990).

    Article  PubMed  CAS  Google Scholar 

  14. SE Kim, SH Song, YP Yun, et al., The effect of immobilization of heparin and bone morphogenic protein-2 (BMP-2) to titanium surfaces on inflammation and osteoblast function, Biomaterials, 32, 366 (2011).

    Article  PubMed  CAS  Google Scholar 

  15. YJ Lee, Y Kim, JY Kim, et al., Effect of different concentrations of Escherichia coli-derived rhBMP-2 coating on osseointegration of Implants in dogs, Tissue Eng Regen Med, 9, 209 (2012).

    Article  CAS  Google Scholar 

  16. DL Diefenderfer, AM Osyczka, JP Garino, et al., Regulation of BMP-induced transcription in cultured human bone marrow stromal cells, J Bone Joint Surg Am, 85A, 19 (2003).

    Google Scholar 

  17. F Lecanda, LV Avioli, SL Cheng, et al., Regulation of bone matrix protein expression and induction of differentiation of human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2, J Cell Biochem, 67, 386 (1997).

    Article  PubMed  CAS  Google Scholar 

  18. S Itoh, M Matubara, T Kawauchi, et al., Enhancement of bone ingrowth in a titanium fiber mesh implant by rhBMP-2 and hyaluronic acid, J Mater Sci Mater Med, 12, 575 (2001).

    Article  PubMed  CAS  Google Scholar 

  19. Z Shi, KG Neoh, ET Kang, et al., Titanium with surface-grafted dextran and immobilized bone morphogenetic protein-2 for inhibition of bacterial adhesion and enhancement of osteoblast functions, Tissue Eng Part A, 15, 417 (2009).

    Article  PubMed  CAS  Google Scholar 

  20. Z Shi, KG Neoh, ET Kang, et al., Surface functionalization of titanium with carboxymethyl chitosan and immobilized bone morphogenetic protein-2 for enhanced osseointegration, Biomacromolecules, 10, 1603 (2009).

    Article  PubMed  CAS  Google Scholar 

  21. B Wen, M Karl, D Pendrys, et al., An evaluation of BMP-2 delivery from scaffolds with miniaturized dental implants in a novel rat mandible model, J Biomed Mater Res B Appl Biomater, 97, 315 (2011).

    PubMed  Google Scholar 

  22. DW Lee, YP Yun, K Park, et al., Gentamicin and bone morphogenic protein-2 (BMP-2)-delivering heparinizedtitanium implant with enhanced antibacterial activity and osteointegration, Bone, 50, 974 (2012).

    Article  PubMed  CAS  Google Scholar 

  23. R Sasisekharan, S Ernst, G Venkataraman, et al., On the regulation of fibroblast growth factor activity by heparin-like glycosaminoglycans, Angiogenesis, 1, 45 (1997).

    Article  PubMed  CAS  Google Scholar 

  24. AR Holmberg, UH Lerner, AA Alayia, et al., Development of a novel poly bisphosphonate conjugate for treatment of skeletal metastasis and osteoporosis, Int J Oncol, 37, 563 (2010).

    Article  PubMed  CAS  Google Scholar 

  25. I Lambrinoudaki, G Christodoulakos, D botsis, et al., Bisphosphonates, Ann N Y Acad Sci, 1092, 397 (2006).

    Article  PubMed  CAS  Google Scholar 

  26. NJ Malden, AY Pai, Oral bisphosphonate associated osteonecrosis of the jaws: three case reports, Br Dent J, 203, 93 (2007).

    Article  PubMed  CAS  Google Scholar 

  27. S Oura, H Tanino, T Yoshimasu, et al., Bisphosphonate therapy for bone metastases from breast cancer: clinical results and a new therapeutic approach, Breast Cancer, 7, 307 (2000).

    Article  PubMed  CAS  Google Scholar 

  28. RG Russell, Bisphosphonates: from bench to bedside, Ann N Y AcadSci, 1068, 367 (2006).

    Article  CAS  Google Scholar 

  29. RG Russell, Z Xia, JE Dunford, et al., Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy, Ann N Y Acad Sci, 1117, 209 (2007).

    Article  PubMed  CAS  Google Scholar 

  30. SL Silverman, Paget disease of bone: therapeutic options, J Clin Rheumatol, 14, 299 (2008).

    Article  PubMed  Google Scholar 

  31. Y Inoue, I Hisa, S Seino, et al., Alendronate induces mineralization in mouse osteoblastic MC3T3-E1 cells: regulation of mineralization-related genes, Exp Clin Endocrinol Diabetes, 118, 719 (2010).

    Article  PubMed  CAS  Google Scholar 

  32. HK Kim, JH Kim, AA Abbas, et al., Alendronate enhances osteogenic differentiation of bone marrow stromal cells: a preliminary study, Clin Orthop Relat Res, 467, 3121 (2009).

    Article  PubMed  Google Scholar 

  33. S Panzavolta, P Torricelli, B Bracci, et al., Functionalization of biomimetic calcium phosphate bone cements with alendronate, J Inorg Biochem, 104, 1099 (2010).

    Article  PubMed  CAS  Google Scholar 

  34. F von Knoch, C Jaquiery, M Kowalsky, et al., Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells, Biomaterials, 26, 6941 (2005).

    Article  Google Scholar 

  35. CZ Wang, SM Chen, CH Chen, et al., The effect of the local delivery of alendronate on human adipose-derived stem cellbased bone regeneration, Biomaterials, 31, 8674 (2010).

    Article  PubMed  CAS  Google Scholar 

  36. HJ Moon, YP Yun, CW Han, et al., Effect of heparin and alendronate coating on titanium surfaces on inhibition of osteoclast and enhancement of osteoblast function, Bio chem Biophys Res Commun, 413, 194 (2011).

    Article  CAS  Google Scholar 

  37. SE Kim, DH Suh, YP Yun, et al., Local delivery of alendronate eluting chitosan scaffold can effectively increase osteoblast functions and inhibit osteoclast differentiation, J Mater Sci Mater Med, 23, 2739 (2012).

    Article  PubMed  CAS  Google Scholar 

  38. PH Chua, KG Neoh, ET Kang, et al., Wang Surface functionalization of titanium with hyaluronic acid/chitosan polyelectrolyte multilayers and RGD for promoting osteoblast functions and inhibiting bacterial adhesion, Biomaterials, 29, 1412 (2008).

    Article  PubMed  CAS  Google Scholar 

  39. T Ishibe, T Goto, T Kodama, et al., Bone formation on apatitecoated titanium with incorporated BMP-2/heparin in vivo, Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 108, 867 (2009).

    Article  PubMed  Google Scholar 

  40. JS Park, K Park, DG Woo, et al., Triple constructs consisting of nanoparticles and microspheres for bone-marrow-derived stromal-cell-delivery microscaffolds, Small, 4, 1950 (2008).

    Article  PubMed  CAS  Google Scholar 

  41. I Pountos, T Georgouli, K Henshaw, et al., The effect of bone morphogenic protein-2, bone morphogenic protein-7, parathyroid hormone, and platelet-derived growth factor on the proliferation and osteogenic differentiation of mesenchymal stem cells derived from osteoporotic bone, J Orthop Trauma, 24, 552 (2010)

    Article  PubMed  Google Scholar 

  42. PL Kuo, YT Huang, CH Chang, et al., Bone morphogenic protein-2 and -4 (BMP-2 and -4) mediates fraxetin-induced maturation and differentiation in human osteoblast-like cell lines, Biol Pharm Bull, 29, 119 (2006).

    Article  PubMed  CAS  Google Scholar 

  43. K Turksen, U Bhargava, HK Moe, et al., Isolation of monoclonal antibodies recognizing rat bone-associated molecules in vitro and in vivo, J Histochem Cytochem, 40, 1339 (1992).

    Article  PubMed  CAS  Google Scholar 

  44. JJ van den Beucken, XF Walboomers, OC Boerman, et al., Functionalization of multilayered DNA-coatings with bone morphogenetic protein 2, J Control Release, 113, 63 (2006).

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Medical College, Guro Hospital, #80, Guro-dong, Guro-gu, Seoul, 152-703, Korea

    Sung Eun Kim, Young-Pil Yun & Hak-Jun Kim

  2. Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, 192-1 Hyoja 2-dong, Chuncheon, Gangwon-do, 200-701, Korea

    Kyeongsoon Park

  3. Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Kyung Hee University Dental Hospital at Gangdong, #149 Sangil-dong, Gangdong-gu, Seoul, 134-727, Korea

    Deok-Won Lee

  4. Department of Orthopedic Surgery, Korea University Medical College, Ansan Hospital, Gojan 1-dong, Danwon-gu, Gyeonggi-do, 425-707, Korea

    Jung Wook Kim & Dong Hun Suh

  5. Institute of Cell & Tissue Engineering, Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea, #505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea

    Dae Hyeok Yang

Authors
  1. Sung Eun Kim
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  2. Young-Pil Yun
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  3. Kyeongsoon Park
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  4. Hak-Jun Kim
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  5. Deok-Won Lee
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  6. Jung Wook Kim
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  8. Dong Hun Suh
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Correspondence to Dong Hun Suh.

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These authors contributed equally to this paper

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Kim, S.E., Yun, YP., Park, K. et al. The effects of functionalized titanium with alendronate and bone morphogenic protein-2 for improving osteoblast activity. Tissue Eng Regen Med 10, 353–361 (2013). https://doi.org/10.1007/s13770-013-1098-5

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  • DOI: https://doi.org/10.1007/s13770-013-1098-5

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