PMID- 28232253 OWN - NLM STAT- MEDLINE DCOM- 20180213 LR - 20220330 IS - 1878-7568 (Electronic) IS - 1742-7061 (Linking) VI - 53 DP - 2017 Apr 15 TI - The influence of controlled surface nanotopography on the early biological events of osseointegration. PG - 559-571 LID - S1742-7061(17)30132-0 [pii] LID - 10.1016/j.actbio.2017.02.026 [doi] AB - The early cell and tissue interactions with nanopatterned titanium implants are insufficiently described in vivo. A limitation has been to transfer a pre-determined, well-controlled nanotopography to 3D titanium implants, without affecting other surface parameters, including surface microtopography and chemistry. This in vivo study aimed to investigate the early cellular and molecular events at the bone interface with screw-shaped titanium implants superimposed with controlled nanotopography. Polished and machined titanium implants were firstly patterned with 75-nm semispherical protrusions. Polished and machined implants without nano-patterns were designated as controls. Thereafter, all nanopatterned and control implants were sputter-coated with a 30nm titanium layer to unify the surface chemistry. The implants were inserted in rat tibiae and samples were harvested after 12h, 1d and 3d. In one group, the implants were unscrewed and the implant-adherent cells were analyzed using quantitative polymerase chain reaction. In another group, implants with surrounding bone were harvested en bloc for histology and immunohistochemistry. The results showed that nanotopography downregulated the expression of monocyte chemoattractant protein-1 (MCP-1), at 1d, and triggered the expression of osteocalcin (OC) at 3d. This was in parallel with a relatively lower number of recruited CD68-positive macrophages in the tissue surrounding the nanopatterned implants. Moreover, a higher proportion of newly formed osteoid and woven bone was found at the nanopatterned implants at 3d. It is concluded that nanotopography, per se, attenuates the inflammatory process and enhances the osteogenic response during the early phase of osseointegration. This nanotopography-induced effect appeared to be independent of the underlying microscale topography. STATEMENT OF SIGNIFICANCE: This study provides a first line of evidence that pre-determined nanopatterns on clinically relevant, screw-shaped, titanium implants can be recognized by cells in the complex in vivo environment. Until now, most of the knowledge relating to cell interactions with nanopatterned surfaces has been acquired from in vitro studies involving mostly two-dimensional nanopatterned surfaces of varying chemical composition. We have managed to superimpose pre-determined nanoscale topography on polished and micro-rough, screw-shaped, implants, without changes in the microscale topography or chemistry. This was achieved by colloidal lithography in combination with a thin titanium film coating on top of both nanopatterned and control implants. The early events of osseointegration were evaluated at the bone interface to these implants. The results revealed that nanotopography, as such, elicits downregulatory effects on the early recruitment and activity of inflammatory cells while enhancing osteogenic activity and woven bone formation. CI - Copyright (c) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. FAU - Karazisis, Dimitrios AU - Karazisis D AD - Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden; Department of Oral and Maxillofacial Surgery, Sahlgrenska Academy, University of Gothenburg, Sweden. FAU - Petronis, Sarunas AU - Petronis S AD - BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden; Chemistry, Materials and Surfaces, SP Technical Research Institute of Sweden, Boras, Sweden. FAU - Agheli, Hossein AU - Agheli H AD - Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden. FAU - Emanuelsson, Lena AU - Emanuelsson L AD - Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden. FAU - Norlindh, Birgitta AU - Norlindh B AD - Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden. FAU - Johansson, Anna AU - Johansson A AD - Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden. FAU - Rasmusson, Lars AU - Rasmusson L AD - BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden; Department of Oral and Maxillofacial Surgery, Sahlgrenska Academy, University of Gothenburg, Sweden. FAU - Thomsen, Peter AU - Thomsen P AD - Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden. FAU - Omar, Omar AU - Omar O AD - Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden. Electronic address: omar.omar@biomaterials.gu.se. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170221 PL - England TA - Acta Biomater JT - Acta biomaterialia JID - 101233144 RN - 0 (Bone Substitutes) RN - D1JT611TNE (Titanium) SB - IM MH - Animals MH - Bone Substitutes/*chemistry MH - Cell Adhesion/physiology MH - Cells, Cultured MH - Male MH - Nanoparticles/*chemistry/ultrastructure MH - Osseointegration/*physiology MH - Osteoblasts/*cytology/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Surface Properties MH - Tibia/cytology/*physiology MH - Titanium/*chemistry OTO - NOTNLM OT - Gene expression OT - In vivo OT - Nanotopography OT - Osseointegration OT - Titanium EDAT- 2017/02/25 06:00 MHDA- 2018/02/14 06:00 CRDT- 2017/02/25 06:00 PHST- 2016/08/24 00:00 [received] PHST- 2017/02/06 00:00 [revised] PHST- 2017/02/13 00:00 [accepted] PHST- 2017/02/25 06:00 [pubmed] PHST- 2018/02/14 06:00 [medline] PHST- 2017/02/25 06:00 [entrez] AID - S1742-7061(17)30132-0 [pii] AID - 10.1016/j.actbio.2017.02.026 [doi] PST - ppublish SO - Acta Biomater. 2017 Apr 15;53:559-571. doi: 10.1016/j.actbio.2017.02.026. Epub 2017 Feb 21.