Bio-Nano Interfaces and Engineering Applications: Bio-Nano Interfaces: Biomedical Applications
Sponsored by: TMS Functional Materials Division, TMS Structural Materials Division, TMS: Biomaterials Committee
Program Organizers: Candan Tamerler, University of Kansas; John Nychka, University of Alberta; Kalpana Katti, North Dakota State University; Terry Lowe, Colorado School of Mines

Monday 2:00 PM
February 27, 2017
Room: Pacific 21
Location: Marriott Marquis Hotel

Session Chair: Feride Sermin Utku, Yeditepe University; Jaroslaw Drelich, Michigan Technological University

2:00 PM  Keynote
The Role of Silica in Composite Materials for Bioengineering Applications Including Bone Regeneration and Cell Based Therapies- The Importance of the Interface: Carole Perry1; 1Nottingham Trent University
    The presence of silica in biomineralized structures of organisms from single celled diatoms through higher plants and primitive animals such as sponges is relatively well known. In addition, although the microscopic and macroscopic structures can be observed in some detail, the chemical and biochemical processes giving rise to such fantastically well organised structures is incompletely understood. What is even less well understood is the effect(s) that silica and its constituent components can have on the biochemical processes of other cells. In this contribution experimental data will be presented describing (1) how the surface chemistry of silica moderates interaction with biomolecules such as small peptides, (2) the effect of ‘silica’ as a component of silk-silica composites on the upregulation of biochemical markers associated with bone regeneration, (3) silica materials as effective tissue culture surfaces for use in the study of cancer,and (4) the development of new methods to study siliceous structures.

2:40 PM  
Silica Nanostructured Platform for Affinity Capture of Tumor-Derived Exosomes: Parissa Ziaei1; Jonathan Geruntho1; Oscar Marin-Flores1; Clifford Berkman1; M. Grant Norton1; 1Washington State University
    Developing effective and high-throughput selective capture technology for positive prostate-specific membrane antigen (PSMA+) exosomes is critical for early diagnostic and prognostic evaluation of prostate cancer treatment. It is known that the prostate tumor enzyme-biomarker, prostate-specific membrane antigen (PSMA) is highly enriched in exosomes excreted by PSMA+ prostate cancer cells. Using PSMA+ LNCaP cells, the secreted exosomes were collected and isolated from the cultured media. A novel biofunctionalized silica nanostructure was designed to selectivity capture tumor-derived exosomes through the interaction of the TG97 ligand with PSMA on the exosomes. The biocinchonic acid (BCA) assay demonstrates both specific and non-specific exosome capture and high capture efficiency for the ligand-activated silica nanostructures.

3:00 PM  Invited
Nanometrically Smooth Ultrafine Grained Titanium Alloy Surfaces: Paige Stock1; Casey Davis1; Rebecca Reiss2; Terry Lowe1; 1Colorado School of Mines; 2New Mexico Tech
    Recent studies of mesenchymal stem cells, osteoblast-like SaOs-2 cells, MC3T3-E1 pre-osteoblast cells on titanium have shown accelerated growth and enhanced cell viability responses. One study shows a positive correlation between cell viability and nanometer scale surface roughness, but on surfaces with differing grain boundary densities and textures. The differences in cell viability have been hypothesized to be associated with nanometer-scale roughness effects on integrin-linked mechanotransduction pathways. In this study, we show techniques to prepare stochastic nano-scale rough surfaces for comparison via cell proliferation assays on ultrafine grained variants of titanium alloys for dental and orthopedic applications.

3:30 PM Break

3:50 PM  Invited
Engineered Bio-Nano Interfaces of Titanium Biomedical Implants: Sermin Utku1; 1Yeditepe University, Faculty of Engineering, Department of Biomedical Engineering
    cpTi and Ti alloys are used as permanent load-bearing dental and orthopedic implants, which, through the modification of surface roughness, chemistry and wettability using mechanical, chemical and electrical means, have attained optimal osteointegrative properties and long-term mechanical stability. Nanotubular and micro-mesoporous surfaces as biomimetic replicas of biological materials with surface porosity arranged from the macroscale of Ti metal to the micro-nanoscale metal oxide with nanocrystalline mineral layer enable enhanced bone regeneration, indicating that the metal-tissue interface needs to be dealt with at the molecular scale. Coating surfaces with bio-modulated interfaces, bifunctional molecular probes, offers a wide range of opportunities to design and fabricate novel interfaces. Modification of implant surfaces has enhanced biocompatibility of the implant surface, enabling attachment of fibrin and osteogenic cells, production of ECM, direct bone formation on the implant surface, adhesion of platelets, colonization of osteoblasts and osteointegration with less bone resorption.

4:20 PM  Invited
Early Study on Surface Nano-engineering of Endovascular Zinc Implants and Resulting Effects on Biodegradation and Biocompatiblity: Adam Drelich1; Roger Guillory1; Jeremy Goldman1; Jaroslaw Drelich1; 1Michigan Technological University
    Recent in vivo study with zinc (Zn) revealed that this material biodegrades at varying rates over time, with slower degradation occurring in the first few weeks due to a surface oxide film. This intriguing, yet unexplained phenomenon prompted us to introduce a revolutionary concept in engineering biodegradable stents: stents with a graded degradation rate. In this study, both thickness and structure of an oxide film on Zn are manipulated through oxidation, electropolishing and anodization. Zinc wires of different surface finish were implanted into the abdominal aorta lumens of rats for up to 8 weeks, per our vascular implant model, to assess the degradation rate and corrosion uniformity, identify corrosion products, assess biocompatibility of blood borne and vascular cells, quantify smooth muscle cell intimal hyperplasia, and assess toxicity. Our results reveal striking differences in in vivo corrosion rates and provide fundamental insights into how zinc corrosion regulates inflammation and neointimal hyperplasia.

4:50 PM  
A Bone-mimetic 3D Metastasis Cancer Tumor Model: Kalpana Katti1; MD Shahjahan Molla1; Sumanta Kar1; Dinesh Katti1; 1North Dakota State University
    Many cancers have a propensity to metastasize to bone with prostate and breast cancer in particular. Here we report development of a novel tissue engineered bone mimetic nanoclay based scaffold that creates a bone-mimetic environment in vitro. This scaffold is used with a novel sequential seeding technique to develop prostate and breast cancer tumoroids. The 3D system provides a new test bed to study cancer biology as well the metastasis to bone. Genetic studies using qRT-PCR experiments were performed to evaluate the expressions of key genes related to osteoblastic bone metastasis of prostate and breast cancer. Our gene expression analysis suggests that the bone-mimetic environment in the cancer test-bed mimics the mesenchymal to epithelial transition (MET) stage of metastasis. The biomimetic scaffold system presented here represents an excellent invitro environment for study of tumor formation and cancer metastasis that enhances animal model studies.

5:10 PM  
Nanostructured Surfaces for Dental Implant Applications: Carlos Elias1; Daniel Fernandes1; 1Instituto Militar de Engenharia
    The development of new biomaterials is a constant in dentistry. Much from an adequate performance of an implant comes from its surface. . The most relevant properties involved are roughness, surface energy, surface charge, wettability and chemical composition. Surface treatment improves the primary (mechanical) and secondary (osseointegration) stability of dental implants. Among surfaces modifications the first strategy is the improvement of surface morphology at micro and nanometer level. A nanostructured surface enhances spreading and binding of protein, fibrin and cells. The first strategy is to improve the surface by chemically modifications by incorporating inorganic phases. The second strategy is to change the surface roughness at micro and nano level. Nanotopography can influence cell proliferation and differentiation in osteoblasts. In the present work, in vitro and in vivo tests evaluated the influence of F, Ca and Mg elements in osseointegration. The results were compared with surfaces with micro and nanoroughness features.

5:40 PM  
Modulation of Antimicrobial Peptide Activity at the Medical Implant Interface through Chimeric Peptide Spacer Design: Cate Wisdom1; Sarah VanOosten1; Kyle Boone1; Paul Arnold2; Malcolm Snead3; Candan Tamerler4; 1University of Kansas, Bioengineering Program; 2University of Kansas Medical Center, Department of Neurosurgery; 3The University of Southern California, Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry; 4University of Kansas, Mechanical Engineering Department
    Surgical site infection is a common cause of post-operative morbidity, often leading to implant failure, ultimately requiring revision surgery. Controlling the bio-material interface plays a critical role in reducing infection. We engineered a biomimetic interface, utilizing a novel single molecule to self anchor and bring antimicrobial property to the bio-material interface. Titanium surfaces coated with the engineered peptide showed bacteria reduction up to approximately 10-fold for S. mutans and 50-fold for S. epidermidis. Our design includes offering a spacer design, which is incorporated in between the bioactive domains to improve the functional components. As a result, fibroblast attachment and metabolism at the interface were improved compared to the untreated surface. Biomimetic interfaces formed with this chimeric peptide offer interminable potential by coupling antimicrobial and improved host cell responses to implantable titanium materials, and the peptide based approach is extendable to other applications. Supported by AR06224/NIH-NIAMS, DE025476/NIH-NIDCR.