Enhancement of osseointegration by direct coating of rhBMP-2 on target-ion induced plasma sputtering treated SLA surface for dental application

Abstract

Owing to the excellent bioactive properties of recombinant human bone morphogenetic proteins (rhBMPs), dentistry considers them as a fascinating adjuvant alternative for enhancing bone regeneration and bone-to-implant junction in the early implantation stages. However, stable loading and delivery efficiency of rhBMPs on the implant surfaces involve major concerns because of the harsh wearing condition under load during implantation. In this study, to achieve successful rhBMP-2 delivery, a nanoporous surface structure is introduced on the sandblasting with large grit and acid-etching (SLA)-treated titanium (Ti) surface via the tantalum (Ta) target-ion induced plasma sputtering (TIPS) technique. Unlike oxidation-induced surface nanoporous fabrications on a Ti surface, TIPS-treated surfaces provide excellent structural unity of the nanoporous structure with the substrate due to their etching-based fabrication mechanism. SLA/TIPS-treated Ti exhibits distinct nanoporous structures on the microscale surface geometry and better hydrophilicity compared with SLA-treated Ti. A sufficiently empty nanoporous surface structure combined with the hydrophilic property of SLA/TIPS-treated Ti facilitates the formation of a thick and uniform coating layer of rhBMP-2 on the surface without any macro- and microcoagulation. Compared with the SLA-treated Ti surface, the amount of coated rhBMP-2 increases up to 63% on the SLA/TIPS-treated Ti surface. As a result, the in vitro pre-osteoblast cell response of the SLA/TIPS-treated Ti surface, especially cell adhesion and differentiation behaviors, improves remarkably. A bone-regenerating direct comparison between the rhBMP-2-coated SLA-treated and SLA/TIPS-treated Ti is conducted on a defective dog mandible model. After 8 weeks of implantation surgery, SLA/TIPS-treated Ti with rhBMP-2 exhibits a better degree of contact area for the implanted bone, which mineralizes new bones around the implant. Quantitative results of bone-in-contact ratio and new bone volume also show significantly higher values for the SLA/TIPS-treated Ti with the rhBMP-2 specimen. These results confirm that an SLA/TIPS-treated surface is a suitable rhBMP-2 carrier for a dental implant to achieve early and strong osseointegration of Ti dental implants.

Keywords

Dental implant sandblasting with large grit and acid-etching bone morphogenetic protein nanoporous titanium

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References

Long

Rack

. Titanium alloys in total joint replacement - A materials science perspective. Biomaterials 1998; 19: 1621–1639.

Tengvall

Lundström

. Physico-chemical considerations of titanium as a biomaterial. Clin Mater 1992; 9: 115–134.

Larsson

Thomsen

Aronsson

. Bone response to surface modified titanium implants: Studies on the early tissue response to machined and electropolished implants with different oxide thicknesses. Biomaterials 1996; 17: 605–616.

Le Guehennec

Soueidan

Layrolle

. Surface treatments of titanium dental implants for rapid osseointegration. Dent Mater 2007; 23: 844–854.

Cochran

Buser

Ten Bruggenkate

. The use of reduced healing times on ITI® implants with a sandblasted and acid-etched (SLA) surface: Early results from clinical trials on ITI® SLA implants. Clin Oral Implan Res 2002; 13: 144–153.

Oates

Valderrama

Bischof

. Enhanced implant stability with a chemically modified SLA surface: A randomized pilot study. Int J Oral Max Impl 2007; 22: 755–760.

Bornstein

Lussi

Schmid

. Early loading of nonsubmerged titanium implants with a sandblasted and acid-etched (SLA) surface: 3-Year results of a prospective study in partially edentulous patients. Int J Oral Max Impl 2003; 18: 659–666.

. The roles of PI3K/Akt signaling pathway in regulating MC3T3-E1 preosteoblast proliferation and differentiation on SLA and SLActive titanium surfaces. J Biomed Mater Res A 2013; 101: 748–754.

Rupp

Scheideier

Olshanska

. Enhancing surface free energy and hydrophilicity through chemical modification of microstructured titanium implant surfaces. J Biomed Mater Res A 2006; 76: 323–334.

10.

Mellado Valero

Ferrer García

Herrera Ballester

. Effects of diabetes on the osseointegration of dental implants. Med Oral Patol Oral 2007; 12: E38–43.

11.

Balshi

Wolfinger

. Dental implants in the diabetic patient: A retrospective study. Implant Dent 1999; 8: 355–359.

12.

Huh

Lee

Jeon

. Physical stability of arginine-glycine-aspartic acid peptide coated on anodized implants after installation. J Adv Prosthodont 2013; 5: 84–91.

13.

Bae

Yun

Kim

. Anodic oxidized nanotubular titanium implants enhance bone morphogenetic protein-2 delivery. J Biomed Mater Res B 2010; 93: 484–491.

14.

Chang

Feng

. Fibronectin-grafted titanium dental implants: An in vivo study. BioMed Res Int 2016; 2016.

15.

Liu

Enggist

Kuffer

. The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration. Biomaterials 2007; 28: 2677–2686.

16.

Teng

Chen

Wang

. Effects of osseointegration by bone morphogenetic protein-2 on titanium implants in vitro and in vivo. Bioinorg Chem Appl 2016; 2016: 3837679–3837679.

17.

Schliephake

Aref

Scharnweber

. Effect of immobilized bone morphogenic protein 2 coating of titanium implants on peri-implant bone formation. Clin Oral Implan Res 2005; 16: 563–569.

18.

Jiang

Liu

Peel

. Bone response to the multilayer BMP-2 gene coated porous titanium implant surface. Clin Oral Implan Res 2013; 24: 853–861.

19.

Han

Lin

. BMP2-encapsulated chitosan coatings on functionalized Ti surfaces and their performance in vitro and in vivo. Mater Sci Eng C-Mater 2014; 40: 1–8.

20.

Wang

Guo

Liu

. BMP-functionalised coatings to promote osteogenesis for orthopaedic implants. Int J Mol Sci 2014; 15: 10150–10168.

21.

Jun

Lee

Jang

. Bone morphogenic protein-2 (BMP-2) loaded hybrid coating on porous hydroxyapatite scaffolds for bone tissue engineering. J Mater Sci-Mater Med 2013; 24: 773–782.

22.

Barfeie

Wilson

Rees

. Implant surface characteristics and their effect on osseointegration. Br Dent J 2015; 218: E9–E9.

23.

Liu

Gao

. Role of adsorbed proteins on hydroxyapatite-coated titanium in osteoblast adhesion and osteogenic differentiation. Sci Bull 2015; 60: 691–700.

24.

Kim

Yang

Koh

. Fabrication and characterization of functionally graded nano-micro porous titanium surface by anodizing. J Biomed Mater Res B 2009; 88: 427–435.

25.

Wheeler

. Eight-year clinical retrospective study of titanium plasma-sprayed and hydroxyapatite-coated cylinder implants. Int J Oral Max Impl 1996; 11: 340–350.

26.

Tinsley

Watson

Russell

. A comparison of hydroxylapatite coated implant retained fixed and removable mandibular prostheses over 4 to 6 years. Clin Oral Implan Res 2001; 12: 159–166.

27.

Jang

Kim

Jung

. Large-scale nanopatterning of metal surfaces by target-ion induced plasma sputtering (TIPS). RSC Adv 2016; 6: 23702–23708.

28.

Kim

Choi

Ryu

. The biocompatibility of SLA-treated titanium implants. Biomed Mater 2008; 3: 025011–025011.

29.

Huh

Park

Kim

. Alveolar ridge augmentation using anodized implants coated with Escherichia coli-derived recombinant human bone morphogenetic protein 2. Oral Surg Oral Med O 2011; 112: 42–49.

30.

Huh

Kim

. Effects of anodized implants coated with Escherichia coli-derived rhBMP-2 in beagle dogs. Int J Oral Max Surg 2012; 41: 1577–1584.

31.

Muthukuru

. Bone morphogenic protein-2 induces apoptosis and cytotoxicity in periodontal ligament cells. J Periodontol 2013; 84: 829–838.

32.

Kim

Lee

Ryu

. Effects of rhBMP-2 on sandblasted and acid etched titanium implant surfaces on bone regeneration and osseointegration: Spilt-mouth designed pilot study. BioMed Res Int 2015; 2015: 459393–459393.

33.

Kim

Kang

Choi

. The effect of anodized implants coated with combined rhBMP-2 and recombinant human vascular endothelial growth factors on vertical bone regeneration in the marginal portion of the peri-implant. Oral Surg Oral Med O 2013; 115: e24–31.

34.

Miletić

Terek

Kovačević

. Influence of substrate roughness on adhesion of TiN coatings. J Braz Soc Mech Sci Eng 2013; 36: 293–299.

35.

Varacalle

Guillen

Deason

. Effect of grit-blasting on substrate roughness and coating adhesion. J Therm Spray Technol 2006; 15: 348–355.

36.

Chirico

Cannone

Beretta

. Dynamics of green fluorescent protein mutant2 in solution, on spin-coated glasses, and encapsulated in wet silica gels. Protein Sci 2002; 11: 1152–1161.

37.

Han

Kim

Koh

. Creation of hierarchical micro/nano-porous TiO2 surface layer onto Ti implants for improved biocompatibility. Surf Coat Technol 2014; 251: 226–231.

38.

Yang

Cho

. Comparison between heparin-conjugated fibrin and collagen sponge as bone morphogenetic protein-2 carriers for bone regeneration. Exp Mol Med 2012; 44: 350–355.

39.

Pham

Jang

Jung

. Creation of nanoporous tantalum (Ta)-incorporated titanium (Ti) surface onto Ti implants by sputtering of Ta in Ar under extremely high negative substrate biases. J Mater Chem 2012; 22: 24798–24798.

40.

Shah

Lazatin

Sinha

. Mechanism of BMP-2 stimulated adhesion of osteoblastic cells to titanium alloy. Biol Cell 1999; 91: 131–142.

41.

Lavenus

Louarn

Layrolle

. Nanotechnology and dental implants. Int J Biomater 2010; 2010: 915327–915327.

42.

Lee

Han

Hwang

. Analysis of attachment, proliferation and differentiation response of human mesenchymal stem cell to various implant surfaces coated with rhBMP-2. J Korean Acad Prosthodont 2012; 50: 44–44.

43.

Gautschi

Cadosch

Zellweger

. Apoptosis induction and reduced proliferation in human osteoblasts by rhBMP-2, -4 and -7. J Musculoskelet Neuronal Interact 2009; 9: 53–60.

44.

Ogasawara

Kawaguchi

Jinno

. Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6. Mol Cell Biol 2004; 24: 6560–6568.

45.

Warashina

Sakano

Kitamura

. Biological reaction to alumina, zirconia, titanium and polyethylene particles implanted onto murine calvaria. Biomaterials 2003; 24: 3655–3661.