Surface Engineering of Nanostructured Titanium Implants with Bioactive Ions

Surface nanofeatures and bioactive ion chemical modification are centrally important in current titanium (Ti) oral implants for enhancing osseointegration. However, it is unclear whether the addition of bioactive ions definitively enhances the osteogenic capacity of a nanostructured Ti implant. We systematically investigated the osteogenesis process of human multipotent adipose stem cells triggered by bioactive ions in the nanostructured Ti implant surface. Here, we report that bioactive ion surface modification (calcium [Ca] or strontium [Sr]) and resultant ion release significantly increase osteogenic activity of the nanofeatured Ti surface. We for the first time demonstrate that ion modification actively induces focal adhesion development and expression of critical adhesion–related genes (vinculin, talin, and RHOA) of human multipotent adipose stem cells, resulting in enhanced osteogenic differentiation on the nanofeatured Ti surface. It is also suggested that fibronectin adsorption may have only a weak effect on early cellular events of mesenchymal stem cells (MSCs) at least in the case of the nanostructured Ti implant surface incorporating Sr. Moreover, results indicate that Sr overrides the effect of Ca and other important surface factors (i.e., surface area and wettability) in the osteogenesis function of various MSCs (derived from human adipose, bone marrow, and murine bone marrow). In addition, surface engineering of nanostructured Ti implants using Sr ions is expected to exert additional beneficial effects on implant bone healing through the proper balancing of the allocation of MSCs between adipogenesis and osteogenesis. This work provides insight into the future surface design of Ti dental implants using surface bioactive ion chemistry and nanotopography.

[1]  M. Esposito,et al.  Posterior atrophic jaws rehabilitated with prostheses supported by 6 mm long × 4 mm wide implants or by longer implants in augmented bone. 3-year post-loading results from a randomised controlled trial. , 2018, European journal of oral implantology.

[2]  A. Wennerberg,et al.  Local release of magnesium from mesoporous TiO2 coatings stimulates the peri-implant expression of osteogenic markers and improves osteoconductivity in vivo. , 2014, Acta biomaterialia.

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

[4]  Enateri V. Alakpa,et al.  Nanotopographical induction of osteogenesis through adhesion, bone morphogenic protein cosignaling, and regulation of microRNAs. , 2014, ACS nano.

[5]  Huaidong Jiang,et al.  Nanostructured titanate with different metal ions on the surface of metallic titanium: a facile approach for regulation of rBMSCs fate on titanium implants. , 2014, Small.

[6]  S. Yamano,et al.  Nanometer-scale features on micrometer-scale surface texturing: a bone histological, gene expression, and nanomechanical study. , 2014, Bone.

[7]  Wenjie Zhang,et al.  Magnesium ion implantation on a micro/nanostructured titanium surface promotes its bioactivity and osteogenic differentiation function , 2014, International journal of nanomedicine.

[8]  C. Lim,et al.  Force-dependent vinculin binding to talin in live cells: a crucial step in anchoring the actin cytoskeleton to focal adhesions. , 2014, American journal of physiology. Cell physiology.

[9]  Yong Han,et al.  Direct role of interrod spacing in mediating cell adhesion on Sr-HA nanorod-patterned coatings , 2014, International journal of nanomedicine.

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

[11]  K. Burridge,et al.  Regulation of RhoA Activity by Adhesion Molecules and Mechanotransduction , 2014, Current molecular medicine.

[12]  Wei Chen,et al.  Wnt and the Wnt signaling pathway in bone development and disease. , 2014, Frontiers in bioscience.

[13]  T. Albrektsson,et al.  Immediate occlusal loading of NanoTite™ tapered implants: a prospective 1-year clinical and radiographic study. , 2013, Clinical implant dentistry and related research.

[14]  A. Wennerberg,et al.  Characteristics of 2 Different Commercially Available Implants with or without Nanotopography , 2013, International journal of dentistry.

[15]  K. Isama,et al.  Calcium-incorporated titanium surfaces influence the osteogenic differentiation of human mesenchymal stem cells. , 2013, Journal of biomedical materials research. Part A.

[16]  E. Gultepe,et al.  Fibronectin and vitronectin promote human fetal osteoblast cell attachment and proliferation on nanoporous titanium surfaces. , 2013, Journal of biomedical nanotechnology.

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

[18]  H. Zreiqat,et al.  The synergistic effect of hierarchical micro/nano-topography and bioactive ions for enhanced osseointegration. , 2013, Biomaterials.

[19]  I. Abrahamsson,et al.  Deposition of nanometer scaled calcium-phosphate crystals to implants with a dual acid-etched surface does not improve early tissue integration. , 2013, Clinical oral implants research.

[20]  Jin-Woo Park,et al.  Positive modulation of osteogenesis- and osteoclastogenesis-related gene expression with strontium-containing microstructured Ti implants in rabbit cancellous bone. , 2013, Journal of biomedical materials research. Part A.

[21]  P. Felice,et al.  Posterior atrophic jaws rehabilitated with prostheses supported by 5 x 5 mm implants with a novel nanostructured calcium-incorporated titanium surface or by longer implants in augmented bone. One-year results from a randomised controlled trial. , 2013, European journal of oral implantology.

[22]  H. Kronenberg,et al.  Loss of wnt/β‐catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[23]  P. Marie,et al.  Strontium signaling: molecular mechanisms and therapeutic implications in osteoporosis. , 2012, Pharmacology & therapeutics.

[24]  Tae-Hyun Nam,et al.  Role of subnano-, nano- and submicron-surface features on osteoblast differentiation of bone marrow mesenchymal stem cells. , 2012, Biomaterials.

[25]  Elizabeth G Loboa,et al.  Cytoskeletal and focal adhesion influences on mesenchymal stem cell shape, mechanical properties, and differentiation down osteogenic, adipogenic, and chondrogenic pathways. , 2012, Tissue engineering. Part B, Reviews.

[26]  P. Marie,et al.  Strontium ranelate rebalances bone marrow adipogenesis and osteoblastogenesis in senescent osteopenic mice through NFATc/Maf and Wnt signaling , 2012, Aging cell.

[27]  J. Schrooten,et al.  A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells. , 2012, Biomaterials.

[28]  O. MacDougald,et al.  Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a β-catenin-dependent mechanism. , 2012, Bone.

[29]  Takashi Ushida,et al.  The effect of substrate microtopography on focal adhesion maturation and actin organization via the RhoA/ROCK pathway. , 2011, Biomaterials.

[30]  H. Steveling,et al.  Early and immediate loading of titanium implants with fluoride-modified surfaces: results of 5-year prospective study. , 2011, Clinical oral implants research.

[31]  G. Huynh-Ba,et al.  Early osseointegration to hydrophilic and hydrophobic implant surfaces in humans. , 2011, Clinical oral implants research.

[32]  R. Rullo,et al.  Biological response of human bone marrow mesenchymal stem cells to fluoride-modified titanium surfaces. , 2010, Clinical oral implants research.

[33]  T. Kodama,et al.  Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation. , 2010, The Journal of clinical investigation.

[34]  T. Hanawa,et al.  Osteoblast response and osseointegration of a Ti-6Al-4V alloy implant incorporating strontium. , 2010, Acta biomaterialia.

[35]  Je-Yong Choi,et al.  Adiponectin Stimulates Osteoblast Differentiation Through Induction of COX2 in Mesenchymal Progenitor Cells , 2009, Stem cells.

[36]  Shelly R. Peyton,et al.  ECM Compliance Regulates Osteogenesis by Influencing MAPK Signaling Downstream of RhoA and ROCK , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[37]  T. Peltola,et al.  Effect of hydroxyapatite and titania nanostructures on early in vivo bone response. , 2008, Clinical implant dentistry and related research.

[38]  Jin-Woo Park,et al.  Effects of calcium ion incorporation on osteoblast gene expression in MC3T3-E1 cells cultured on microstructured titanium surfaces. , 2008, Journal of biomedical materials research. Part A.

[39]  Christoph Ballestrem,et al.  Vinculin controls focal adhesion formation by direct interactions with talin and actin , 2007, The Journal of cell biology.

[40]  P. Halbout,et al.  Strontium Ranelate Promotes Osteoblastic Differentiation and Mineralization of Murine Bone Marrow Stromal Cells: Involvement of Prostaglandins , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.