Osteogenic Differentiation of Human Mesenchymal Stem Cells Modulated by Surface Manganese Chemistry in SLA Titanium Implants

The manganese (Mn) ion has recently been probed as a potential candidate element for the surface chemistry modification of titanium (Ti) implants in order to develop a more osteogenic surface with the expectation of taking advantage of its strong binding affinity to the integrins on bone-forming cells. However, the exact mechanism of how Mn enhances osteogenesis when introduced into the surface of Ti implants is not clearly understood. This study investigated the corrosion resistance and potential osteogenic capacity of a Mn-incorporated Ti surface as determined by electrochemical measurement and examining the behaviors of human mesenchymal stem cells (MSCs) in a clinically available sandblasted/acid-etched (SLA) oral implant surface intended for future biomedical applications. The surface that resulted from wet chemical treatment exhibited the formation of a Mn-containing nanostructured TiO2 anatase thin film in the SLA implant and improved corrosion resistance. The Mn-incorporated SLA surface displayed sustained Mn ion release and enhanced osteogenesis-related MSC function, which enhanced early cellular events such as spreading, focal adhesion, and mRNA expression of critical adhesion-related genes and promoted full human MSC differentiation into mature osteoblasts. Our findings indicate that surface Mn modification by wet chemical treatment is an effective approach to produce a Ti implant surface with increased osteogenic capacity through the promotion of the osteogenic differentiation of MSCs. The improved corrosion resistance of the resultant surface is yet another important benefit of being able to provide favorable osseointegration interface stability with an increased barrier effect.

[1]  C. Grandini,et al.  Development of novel Ti-Mo-Mn alloys for biomedical applications , 2020, Scientific Reports.

[2]  A. Boccaccini,et al.  Osteogenic properties of manganese-doped mesoporous bioactive glass nanoparticles. , 2020, Journal of biomedical materials research. Part A.

[3]  Guofeng Bao,et al.  Enhanced osteogenic activity and antibacterial ability of manganese–titanium dioxide microporous coating on titanium surfaces , 2020, Nanotoxicology.

[4]  M. Kaur,et al.  Review on titanium and titanium based alloys as biomaterials for orthopaedic applications. , 2019, Materials science & engineering. C, Materials for biological applications.

[5]  El-Sayed M. Sherif,et al.  Corrosion resistance of coupled sandblasted, large‐grit, acid‐etched (SLA) and anodized Ti implant surfaces in synthetic saliva , 2019, Clinical and experimental dental research.

[6]  T. Hanawa,et al.  The relative effects of Ca and Mg ions on MSC osteogenesis in the surface modification of microrough Ti implants , 2019, International journal of nanomedicine.

[7]  Julian R. Jones,et al.  Osteogenic potential of sol–gel bioactive glasses containing manganese , 2019, Journal of Materials Science: Materials in Medicine.

[8]  G. Stein,et al.  Participation of integrin β3 in osteoblast differentiation induced by titanium with nano or microtopography. , 2019, Journal of biomedical materials research. Part A.

[9]  R. Cabrini,et al.  Research on implants and osseointegration , 2019, Periodontology 2000.

[10]  Jin-Woo Park,et al.  Multifunctional effects of a modification of SLA titanium implant surface with strontium-containing nanostructures on immunoinflammatory and osteogenic cell function. , 2018, Journal of biomedical materials research. Part A.

[11]  Jin-Woo Park,et al.  Osteogenic differentiation of mesenchymal stem cells modulated by a chemically modified super-hydrophilic titanium implant surface , 2018, Journal of biomaterials applications.

[12]  F. Kloss,et al.  A comparative in vivo study of strontium-functionalized and SLActive™ implant surfaces in early bone healing , 2018, International journal of nanomedicine.

[13]  Yuanzhong Zhou,et al.  In vivo neutron activation analysis of bone manganese in workers , 2018, Physiological measurement.

[14]  M. Aschner,et al.  Manganese metabolism in humans. , 2018, Frontiers in bioscience.

[15]  F. Tarlochan,et al.  Corrosion and surface modification on biocompatible metals: A review. , 2017, Materials science & engineering. C, Materials for biological applications.

[16]  G. Kotsakis,et al.  Increased Levels of Dissolved Titanium Are Associated With Peri‐Implantitis – A Cross‐Sectional Study , 2017, Journal of periodontology.

[17]  Xuanyong Liu,et al.  Mn-containing titanium surface with favorable osteogenic and antimicrobial functions synthesized by PIII&D. , 2017, Colloids and surfaces. B, Biointerfaces.

[18]  M. Esposito,et al.  Early loading of maxillary titanium implants with a nanostructured calcium-incorporated surface (Xpeed): 5-year results from a multicentre randomised controlled trial. , 2017, European Journal of Oral Implantology.

[19]  C. Ballestrem,et al.  Mechanosensitive components of integrin adhesions: Role of vinculin , 2016, Experimental cell research.

[20]  J. Jang,et al.  Surface Engineering of Nanostructured Titanium Implants with Bioactive Ions , 2016, Journal of dental research.

[21]  Tingting Ding,et al.  Osteoinduction and long-term osseointegration promoted by combined effects of nitrogen and manganese elements in high nitrogen nickel-free stainless steel. , 2016, Journal of materials chemistry. B.

[22]  M. Niinomi,et al.  Microstructures, mechanical properties and cytotoxicity of low cost beta Ti-Mn alloys for biomedical applications. , 2015, Acta biomaterialia.

[23]  A. Wennerberg,et al.  Influence of Temperature and Acid Etching Time on the Superficial Characteristics of Ti , 2015 .

[24]  Wei Zheng,et al.  Manganese Toxicity Upon Overexposure: a Decade in Review , 2015, Current Environmental Health Reports.

[25]  Yangho Kim,et al.  Blood Metal Concentrations of Manganese, Lead, and Cadmium in Relation to Serum Ferritin Levels in Ohio Residents , 2015, Biological Trace Element Research.

[26]  Zhuxian Zhou,et al.  Dendritic nanoglobules with polyhedral oligomeric silsesquioxane core and their biomedical applications. , 2014, Nanomedicine.

[27]  P. Bogdanoff,et al.  Evaluation of MnOx, Mn2O3, and Mn3O4 Electrodeposited Films for the Oxygen Evolution Reaction of Water , 2014 .

[28]  J. Qin,et al.  Mechanisms of talin-dependent integrin signaling and crosstalk. , 2014, Biochimica et biophysica acta.

[29]  J. Kovač,et al.  Improvement to the Corrosion Resistance of Ti-Based Implants Using Hydrothermally Synthesized Nanostructured Anatase Coatings , 2014, Materials.

[30]  Zhenxiang Zhang,et al.  Integrin-mediated osteoblastic adhesion on a porous manganese-incorporated TiO2 coating prepared by plasma electrolytic oxidation , 2013, Experimental and therapeutic medicine.

[31]  P. Marie Targeting integrins to promote bone formation and repair , 2013, Nature Reviews Endocrinology.

[32]  Jin-Woo Park,et al.  Surface characteristics and in vitro biocompatibility of a manganese-containing titanium oxide surface , 2011 .

[33]  Chun‐Sing Lee,et al.  Surface structures and osteoblast response of hydrothermally produced CaTiO3 thin film on Ti–13Nb–13Zr alloy , 2011 .

[34]  Andrea R. Gerson,et al.  Resolving surface chemical states in XPS analysis of first row transition metals, oxides and hydroxides: Sc, Ti, V, Cu and Zn , 2010 .

[35]  R. Nedir,et al.  Titanium hydride and hydrogen concentration in acid-etched commercially pure titanium and titanium alloy implants: a comparative analysis of five implant systems. , 2010, Clinical oral implants research.

[36]  Chi Zhang Transcriptional regulation of bone formation by the osteoblast-specific transcription factor Osx , 2010, Journal of orthopaedic surgery and research.

[37]  B. Boyan,et al.  Direct and indirect effects of microstructured titanium substrates on the induction of mesenchymal stem cell differentiation towards the osteoblast lineage. , 2010, Biomaterials.

[38]  A. Bigi,et al.  Effect of Mg(2+), Sr(2+), and Mn(2+) on the chemico-physical and in vitro biological properties of calcium phosphate biomimetic coatings. , 2009, Journal of inorganic biochemistry.

[39]  M. Biesinger,et al.  Quantitative Chemical State XPS Analysis of First Row Transition Metals, Oxides and Hydroxides , 2008 .

[40]  J. van den Dolder,et al.  The behavior of osteoblast-like cells on various substrates with functional blocking of integrin-β1 and integrin-β3 , 2007, Journal of materials science. Materials in medicine.

[41]  J. Nebe,et al.  Influence of manganese ions on cellular behavior of human osteoblasts in vitro. , 2007, Biomolecular engineering.

[42]  T. Hanawa,et al.  Calcium phosphate formation on titanium by low-voltage electrolytic treatments , 2007, Journal of materials science. Materials in medicine.

[43]  Yueming Jiang,et al.  Cardiovascular toxicities upon managanese exposure , 2007, Cardiovascular Toxicology.

[44]  Lothar Borchers,et al.  Nonalloyed titanium as a bioinert metal--a review. , 2005, Quintessence international.

[45]  C. Rüegg,et al.  Manganese-induced integrin affinity maturation promotes recruitment of αVβ3 integrin to focal adhesions in endothelial cells: evidence for a role of phosphatidylinositol 3-kinase and Src , 2004, Thrombosis and Haemostasis.

[46]  M. Humphries,et al.  Regulation of Integrin α5β1-Fibronectin Interactions by Divalent Cations , 1995, The Journal of Biological Chemistry.