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Bio-Nano Interactions: Synthesis, Functionalization and Characterization of Biomaterial Interfaces
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Current strategies for designing biomaterials involve creating materials and interfaces that interact with biomolecules, cells and tissues.  This thesis aims to investigate several bioactive surfaces, such as nanocrystalline diamond (NCD), hydroxyapatite (HA) and single crystalline titanium dioxide, in terms of material synthesis, surface functionalization and characterization.

Although cochlear implants (CIs) have been proven to be clinically successful, the efficiency of these implants still needs to be improved. A CI typically only has 12-20 electrodes while the ear has approximately 3400 inner hair cells. A type of micro-textured NCD surface that consists of micrometre-sized nail-head-shaped pillars was fabricated. Auditory neurons showed a strong affinity for the surface of the NCD pillars, and the technique could be used for neural guidance and to increase the number of stimulation points, leading to CIs with improved performance.

Typical transparent ceramics are fabricated using pressure-assisted sintering techniques. However, the development of a simple energy-efficient production method remains a challenge. A simple approach to fabricating translucent nano-ceramics was developed by controlling the morphology of the starting ceramic particles. Translucent nano-ceramics, including HA and strontium substituted HA, could be produced via a simple filtration process followed by pressure-less sintering. Furthermore, the application of such materials as a window material was investigated. The results show that MC3T3 cells could be observed through the translucent HA ceramic for up to 7 days. The living fluorescent staining confirmed that the MC3T3 cells were visible throughout the culture period.

Single crystalline rutile possesses in vitro bioactivity, and the crystalline direction affects HA formation. The HA growth on (001), (100) and (110) faces was investigated in a simulated body fluid in the presence of fibronectin (FN) via two different processes. The HA layers on each face were analysed using different characterization techniques, revealing that the interfacial energies could be altered by the pre-adsorbed FN, which influenced HA formation.

In summary, micro textured NCD, and translucent HA and FN functionalized single crystalline rutile, and their interactions with cells and biomimetic HA were studied. The results showed that controlled surface properties are important for enhancing a material’s biological performance.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 37 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1345
Keyword [en]
Bioactive surfaces, nanocrystalline diamond, hydroxyapatite, protein secondary structure, protein absorption, auditory neurons, single crystalline rutile, nano morphology, surface functionalisation, in vitro biomineralisation, translucent nano-ceramics, bio-window material, material characterisation.
National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Materials Science
Identifiers
URN: urn:nbn:se:uu:diva-277121ISBN: 978-91-554-9478-0 (print)OAI: oai:DiVA.org:uu-277121DiVA: diva2:903916
Public defence
2016-06-01, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2016-05-11 Created: 2016-02-17 Last updated: 2016-06-01
List of papers
1. Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond
Open this publication in new window or tab >>Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond
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2016 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 31, 211-220 p.Article in journal (Refereed) Published
Abstract [en]

Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.

Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 5 lm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching.

The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.

The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.

National Category
Medical Materials Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-266956 (URN)10.1016/j.actbio.2015.11.021 (DOI)000370086100019 ()26593784 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 603029
Available from: 2015-11-14 Created: 2015-11-14 Last updated: 2017-12-01Bibliographically approved
2. Fabrication of translucent nanoceramics via a simple filtration method
Open this publication in new window or tab >>Fabrication of translucent nanoceramics via a simple filtration method
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2015 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 5, no 121, 99848-99855 p.Article in journal (Refereed) Published
Abstract [en]

Generally, particle packing density, grain size and morphology are the important factors that affect the transparency of ceramics. In order to achieve better transparency of ceramics, efforts should be developed to eliminate or minimize light scattering or absorption. Therefore the porosity and size of crystals in a ceramic body should be strictly controlled. Typical transparent ceramics are fabricated by pressure-assisted sintering techniques such as hot isostatic pressing (HIP), spark plasma sintering (SPS), and pressure-less sintering (PLS). However, a simple energy efficient production method remains a challenge. In this study, we describe a simple fabrication process via a facile filtration system that can fabricate translucent hydroxyapatite based ceramics. The translucent pieces yielded from filtration exhibit optical transmittance that was confirmed by UV spectroscopy. Briefly, the morphology and size of ceramic nanoparticles, filtration pressure and filtration time are important parameters to be discussed. Compared with different hydroxyapatite nanoparticles, spherical nanoparticles easily form a densely packed structure, followed by sintered ceramics. When the strontium content in HA increases, the morphology of HA changes from nano-spheres to nano-rods, following a decrease in transparency. A pressure filtration model combining Darcy's law and the Kozeny-Carman relation has been discussed to simulate and explain why the translucent ceramics can be fabricated via such a simple process. This method could be further applied to prepare other translucent functional ceramics by controlling the size and morphology of ceramic particles.

National Category
Nano Technology Chemical Engineering
Identifiers
urn:nbn:se:uu:diva-271611 (URN)10.1039/c5ra17866e (DOI)000365406800033 ()
Funder
Carl Tryggers foundation , 14:525
Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2017-12-01Bibliographically approved
3. Utilization of Translucent Hydroxyapatite Nano-Ceramics as a Bio-Window Material
Open this publication in new window or tab >>Utilization of Translucent Hydroxyapatite Nano-Ceramics as a Bio-Window Material
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2016 (English)In: Nano Advances, Vol. 1, 45-49 p.Article in journal (Refereed) Published
Abstract [en]

Bioceramic materials are importantlyused in the field ofhard tissue engineering. The direct detection of cell response is almost impossible for mostof bioceramics due to theiropaqueness. Thus,the live tracking of cell behavior cannot be performedon these ceramics. In this study, we proposea strategy thatdirect observation of cell growth through hydroxyapatite (HA)ceramics can be realized by employing a translucent hydroxyapatite (tHA) nano-ceramic. We obtained MC3T3 preosteoblast cells and cultured them in the presence of tHA for up to 7 days. The results show that MC3T3cells were able to be seen through the tHA. In addition, live fluorescent staining confirmed that the MC3T3 cells were viable throughout the culture time period. The findings reveal the as-fabricated tHA nano-ceramics can bepotentialas a bio-window material for cell adhesion and proliferation.

National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-277119 (URN)
Available from: 2016-02-17 Created: 2016-02-17 Last updated: 2016-07-26Bibliographically approved
4. Biomineralization on Single Crystalline Rutile: The Modulated Growth of Hydroxyapatite by Fibronectin in a Simulated Body Fluid
Open this publication in new window or tab >>Biomineralization on Single Crystalline Rutile: The Modulated Growth of Hydroxyapatite by Fibronectin in a Simulated Body Fluid
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2016 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 6, 35507-35516 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study is to probe the complex interaction between surface bioactivity and protein adsorption on single crystalline rutile. Our previous studies have shown that single crystalline rutile possessed in vitro bioactivity and the crystalline faces affected the hydroxyapatite (HA) formation. However, upon implantation, a fast adsorption of proteins, from the biological fluids, is intermediated by a water layer towards the biomaterial interface. Thus the effect of protein on the bioactivity must be addressed. In this study, the HA growth dynamics on (001), (100) and (110) faces was investigated in a simulated body fluid with the presence of fibronectin (FN) by two different processes. The surface adhesion of each face before and after FN adsorption, as revealed by direct numerical values, was determined by atomic force microscopy (AFM) based peak force quantitative nanomechanical mapping (PF-QNM) for the first time. The findings suggest the surface energies of FN pre-adsorbed (001), (100) and (110) faces have been enhanced, leading to the subsequent accelerated HA formation. Furthermore, (001) and (100) faces were found to have larger coverage of HA crystals than (110) face at an early stage. In addition, various characterizations were performed to probe the chemical and crystal structures of as-grown biomimetic HA crystals, and in particular, the Ca/P ratio variations at different soaking time points.

National Category
Engineering and Technology Materials Chemistry
Identifiers
urn:nbn:se:uu:diva-277120 (URN)10.1039/C6RA04303H (DOI)000374349600042 ()
Available from: 2016-02-17 Created: 2016-02-17 Last updated: 2017-11-30Bibliographically approved

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