Tuning Chemistry and Topography of Nanoengineered Surfaces to Manipulate Immune Response for Bone Regeneration Applications.

Osteoimmunomodulation has informed the importance of modulating a favorable osteoimmune environment for successful materials-mediated bone regeneration. Nanotopography is regarded as a valuable strategy for developing advanced bone materials, due to its positive effects on enhancing osteogenic differentiation. In addition to this direct effect on osteoblastic lineage cells, nanotopography also plays a vital role in regulating immune responses, which makes it possible to utilize its immunomodulatory properties to create a favorable osteoimmune environment. Therefore, the aim of this study was to advance the applications of nanotopography with respect to its osteoimmunomodulatory properties, aiming to shed further light on this field. We found that tuning the surface chemistry (amine or acrylic acid) and scale of the nanotopography (16, 38, and 68 nm) significantly modulated the osteoimmune environment, including changes in the expression of inflammatory cytokines, osteoclastic activities, and osteogenic, angiogenic, and fibrogenic factors. The generated osteoimmune environment significantly affected the osteogenic differentiation of bone marrow stromal cells, with carboxyl acid-tailored 68 nm surface nanotopography offering the most promising outcome. This study demonstrated that the osteoimmunomodulation could be manipulated via tuning the chemistry and nanotopography, which implied a valuable strategy to apply a "nanoengineered surface" for the development of advanced bone biomaterials with favorable osteoimmunomodulatory properties.

[1]  C. Murphy,et al.  Epithelial contact guidance on well-defined micro- and nanostructured substrates , 2003, Journal of Cell Science.

[2]  D. Prockop,et al.  An Alizarin red-based assay of mineralization by adherent cells in culture: comparison with cetylpyridinium chloride extraction. , 2004, Analytical biochemistry.

[3]  Bruce A. Bromberek,et al.  Macrophages influence a competition of contact guidance and chemotaxis for fibroblast alignment in a fibrin gel coculture assay. , 2002, Experimental cell research.

[4]  Ross Crawford,et al.  Osteoimmunomodulatory properties of magnesium scaffolds coated with β-tricalcium phosphate. , 2014, Biomaterials.

[5]  D. Hume,et al.  Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  L. Cooper,et al.  Titanium surface topography alters cell shape and modulates bone morphogenetic protein 2 expression in the J774A.1 macrophage cell line. , 2003, Journal of biomedical materials research. Part A.

[7]  R. Beelen,et al.  Human macrophage polarization in vitro: maturation and activation methods compared. , 2014, Immunobiology.

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

[9]  J. Hamilton,et al.  Proinflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation. , 2009, Osteoarthritis and cartilage.

[10]  Renee V. Goreham,et al.  Small surface nanotopography encourages fibroblast and osteoblast cell adhesion , 2013 .

[11]  J. Lausmaa,et al.  Immune complement activation is attenuated by surface nanotopography , 2011, International journal of nanomedicine.

[12]  Cheng Huang,et al.  Emerging role of microRNAs in regulating macrophage activation and polarization in immune response and inflammation , 2016, Immunology.

[13]  You-Wen He,et al.  Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-κB. , 2012, Immunity.

[14]  Y. Hung,et al.  Control of growth and inflammatory response of macrophages and foam cells with nanotopography , 2012, Nanoscale Research Letters.

[15]  K. Vasilev,et al.  The contribution of inflammasome components on macrophage response to surface nanotopography and chemistry , 2016, Scientific Reports.

[16]  Chengtie Wu,et al.  Nutrient element-based bioceramic coatings on titanium alloy stimulating osteogenesis by inducing beneficial osteoimmmunomodulation. , 2014, Journal of materials chemistry. B.

[17]  B. Alman,et al.  Macrophages Promote Osteoblastic Differentiation In Vivo: Implications in Fracture Repair and Bone Homeostasis , 2015, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  Renee V. Goreham,et al.  pH-tunable gradients of wettability and surface potential , 2012 .

[19]  V. Everts,et al.  The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts , 2015, PloS one.

[20]  Tingting Wang,et al.  Modulation of macrophage phenotype by cell shape , 2013, Proceedings of the National Academy of Sciences.

[21]  David A. Hume,et al.  Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo1 , 2008, The Journal of Immunology.

[22]  A. Michelmore,et al.  Surface Morphology in the Early Stages of Plasma Polymer Film Growth from Amine‐Containing Monomers , 2011 .

[23]  J. Simon,et al.  Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials. , 2011, Biomaterials.

[24]  L. Zitvogel,et al.  Autophagy and cellular immune responses. , 2013, Immunity.

[25]  I. Braceras,et al.  Ion implantation induced nanotopography on titanium and bone cell adhesion , 2014 .

[26]  J. Yeh,et al.  Cell adhesion, morphology and biochemistry on nano-topographic oxidized silicon surfaces. , 2010, European cells & materials.

[27]  U. Lerner,et al.  The role of cytokines in inflammatory bone loss , 2013, Immunological investigations.

[28]  K. Fitzgerald,et al.  Regulation of inflammasome signaling , 2012, Nature Immunology.

[29]  T. Lawrence.  The nuclear factor NF-kappaB pathway in inflammation. , 2009, Cold Spring Harbor perspectives in biology.

[30]  A. Sher,et al.  Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction , 2012, Nature Immunology.

[31]  Chengtie Wu,et al.  Clinoenstatite coatings have high bonding strength, bioactive ion release, and osteoimmunomodulatory effects that enhance in vivo osseointegration. , 2015, Biomaterials.

[32]  Renee V. Goreham,et al.  A substrate independent approach for generation of surface gradients , 2013 .

[33]  Robert A Latour,et al.  Molecular simulation to characterize the adsorption behavior of a fibrinogen gamma-chain fragment. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[34]  J. Wilcox,et al.  Impact of polymer hydrophilicity on biocompatibility: implication for DES polymer design. , 2009, Journal of biomedical materials research. Part A.

[35]  P. Tresco,et al.  Relationships among cell attachment, spreading, cytoskeletal organization, and migration rate for anchorage-dependent cells on model surfaces. , 2000, Journal of biomedical materials research.

[36]  A. Michelmore,et al.  Substrate influence on the initial growth phase of plasma-deposited polymer films. , 2009, Chemical communications.

[37]  J. Elisseeff,et al.  Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells , 2016, Science.

[38]  S. Akira,et al.  Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production , 2008, Nature.

[39]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[40]  Soo Young Lee,et al.  IL-6 is produced by adipose-derived stromal cells and promotes osteogenesis. , 2013, Biochimica et biophysica acta.

[41]  S. Pattingre,et al.  JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. , 2008, Molecular cell.

[42]  M. Schoenfisch,et al.  Interactions of thrombin with fibrinogen adsorbed on methyl-, hydroxyl-, amine-, and carboxyl-terminated self-assembled monolayers. , 2005, Biochemistry.

[43]  Chengtie Wu,et al.  The effect of osteoimmunomodulation on the osteogenic effects of cobalt incorporated β-tricalcium phosphate. , 2015, Biomaterials.

[44]  W. Knoll,et al.  Surface modification of citrate-reduced colloidal gold nanoparticles with 2-mercaptosuccinic acid , 2003 .

[45]  R. Sedev,et al.  Tuning and predicting the wetting of nanoengineered material surface. , 2016, Nanoscale.

[46]  Cahir J. O'Kane,et al.  Complex Inhibitory Effects of Nitric Oxide on Autophagy , 2011, Molecular cell.

[47]  Yusuke Arima,et al.  Effect of wettability and surface functional groups on protein adsorption and cell adhesion using well-defined mixed self-assembled monolayers. , 2007, Biomaterials.

[48]  Shizuo Akira,et al.  Autophagy in infection, inflammation and immunity , 2013, Nature Reviews Immunology.

[49]  K. Vasilev.  Nanoengineered Plasma Polymer Films for Biomaterial Applications , 2014, Plasma Chemistry and Plasma Processing.

[50]  F. Otsuka,et al.  Simvastatin inhibits osteoclast differentiation induced by bone morphogenetic protein-2 and RANKL through regulating MAPK, AKT and Src signaling , 2010, Regulatory Peptides.

[51]  C. Chung,et al.  Expression and Role of Interleukin-6 in Distraction Osteogenesis , 2007, Calcified Tissue International.

[52]  Y. Kadono,et al.  Osteoimmunology: interplay between the immune system and bone metabolism. , 2006, Annual review of immunology.

[53]  M. Hassan,et al.  Titanium With Nanotopography Induces Osteoblast Differentiation by Regulating Endogenous Bone Morphogenetic Protein Expression and Signaling Pathway , 2016, Journal of cellular biochemistry.

[54]  J. Hillier,et al.  A study of the nucleation and growth processes in the synthesis of colloidal gold , 1951 .

[55]  K. Vasilev,et al.  The Role of Surface Nanotopography and Chemistry on Primary Neutrophil and Macrophage Cellular Responses , 2016, Advanced healthcare materials.

[56]  Chengtie Wu,et al.  Multidirectional effects of Sr-, Mg-, and Si-containing bioceramic coatings with high bonding strength on inflammation, osteoclastogenesis, and osteogenesis. , 2014, ACS applied materials & interfaces.

[57]  John A. Jansen,et al.  Understanding the role of nano-topography on the surface of a bone-implant. , 2013, Biomaterials science.

[58]  Yin Xiao,et al.  Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis. , 2016, Acta Biomaterialia.

[59]  Louise E. Smith,et al.  The influence of substrate stiffness gradients on primary human dermal fibroblasts. , 2013, Biomaterials.

[60]  Lonnie D Shea,et al.  Tissue engineering tools for modulation of the immune response. , 2011, BioTechniques.

[61]  J. Tschopp,et al.  A role for mitochondria in NLRP3 inflammasome activation , 2011, Nature.

[62]  Benjamin G Keselowsky,et al.  Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding. , 2004, Biomaterials.

[63]  Y. Bao,et al.  Protumoral TSP50 Regulates Macrophage Activities and Polarization via Production of TNF-α and IL-1β, and Activation of the NF-κB Signaling Pathway , 2015, PloS one.

[64]  Xiao Yin,et al.  Osteoimmunomodulation for the development of advanced bone biomaterials , 2016 .

[65]  D. Williams,et al.  Immune response in biocompatibility. , 1992, Biomaterials.