Bioactive Surgical Implant Coatings with Optional Antibacterial Function

62 Pages·2013·29.94 MB·English

Digital Comprehensive Summaries of Uppsala Dissertations
from the Faculty of Science and Technology 1091
Bioactive Surgical Implant
Coatings with Optional
Antibacterial Function
MIRJAM LILJA
ACTA
UNIVERSITATIS
ISSN 1651-6214
UPSALIENSIS
ISBN 978-91-554-8782-9
UPPSALA
urn:nbn:se:uu:diva-209283
2013
Dissertation presented at Uppsala University to be publicly examined in Room Å2001,
Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, Thursday, 5 December 2013 at 13:00 for
the degree of Doctor of Philosophy. The examination will be conducted in English. Faculty
examiner: Dr. Ing Håvard Haugen (University of Oslo).
Abstract
Lilja, M. 2013. Bioactive Surgical Implant Coatings with Optional Antibacterial Function.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and
Technology 1091. 60 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-8782-9.
Device associated infections are a growing problem in the field of orthopaedics and dentistry.
Bacteria adhering to implant surfaces and subsequent biofilm formation are challenging to treat
with systemic administered antibiotics. Functionalization of implant surfaces with therapeutic
coatings that are capable of inhibiting bacterial adhesion are therefore considered as a straight
forward strategy to treat and prevent implant related infections.
In this thesis, the use of crystalline, arc deposited TiO and biomimetic hydroxyapatite (HA)
2
coatings were evaluated with respect to their potential as antibacterial surface modifications for
bone-anchored implants.
UV light induced photocatalysis of anatase dominated TiO coated surfaces was shown to
2
provide a bactericidal effect against S. epidermidis under clinically relevant illumination times
and doses.
Major parts of the drug release work carried out was based on biomimetic HA (HA-B)
coated fixation pins. The analysis of the coating characteristics revealed that the nanoporous
structure of HA-B coatings in addition to the chemical composition and surface charge are
essential parameters that influence the drug carrier performance. Loading by adsorption was
demonstrated to be a feasible approach to quickly incorporate antibiotics. The controlled release
of antibiotics was shown to facilitate bactericidal effects against S. aureus over application-
relevant time periods, even when exposed to biomechanical forces during insertion into
bone model materials. Antibiotic incorporation during coating growth was shown to promote
somewhat longer drug release time periods than those obtained using adsorption loading.
In summary, functionalization of implant surfaces with bioactive and biocompatible coatings
is a promising concept to impact the clinical success for bone-anchored applications. The
additional feature of optional, on-demand antibacterial properties of these coatings through
either on-site drug release or photocatalytic antibacterial treatment is advantageous for the
prevention and effective treatment of devices-associated infections. Both strategies provide an
immediate response to the implant contamination by bacteria and are believed to contribute
towards minimizing the origin of post-surgical infections, while at the same time improving the
interfacial stability between implant and bone.
Keywords: Hydroxyapatite, titanium dioxide, photocatalysis, antibacterial effect, antibiotic
release, biomimetic coating, co-precipitation, tobramycin
Mirjam Lilja, Department of Engineering Sciences, Nanotechnology and Functional
Materials, Box 534, Uppsala University, SE-75121 Uppsala, Sweden.
© Mirjam Lilja 2013
ISSN 1651-6214
ISBN 978-91-554-8782-9
urn:nbn:se:uu:diva-209283 (http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-209283)
To those who are
passionately curious

List of Papers
This thesis is based on the following papers, which are referred to in the text
by their Roman numerals.

I Lilja, M., Welch K., Åstrand M., Engqvist H., Strømme M.
(2012) Effect of deposition parameters on the photocatalytic ac-
tivity and bioactivity of TiO thin films deposited by vacuum
2
arc on Ti-6Al-4V substrates. J Biomed Mater Res B, 100B
(4):1078–85

II Lilja, M., Forsgren, J., Welch K., Åstrand M., Engqvist H.,
Strømme M. (2012) Photocatalytic and antimicrobial properties
of surgical implant coatings of titanium dioxide deposited
through cathodic arc evaporation. Biotech Lett, 34(12):2299-305

III Lilja M., Lindahl C., Xia W., Engqvist H., Strømme M. (2013)
The Effect of Si-doping on the Release of Antibiotic from Hy-
droxyapatite Coatings. J Biomater Nanobiotech, 4(3):237-41

IV Lilja M., Sörensen J.H., Brohede U., Åstrand M., Procter P.,
Arnolid J., Steckel H., Strømme M. (2013) Drug loading and re-
lease of Tobramycin from hydroxyapatite coated fixation pins. J
Mater Sci: Mater Med, 24 (9):2265-2274

V Sörensen J.H., Lilja M., Sörensen T., Åstrand M., Procter P.,
Strømme M., Steckel H. (2013) Co-precipitation of Tobramycin
into biomimetically coated orthopedic fixation pins employing
sub-micron thin seed layers of hydroxyapatite, submitted

VI Sörensen J.H.*, Lilja M.*, Sörensen T., Åstrand M., Procter P.,
Strømme M., Steckel H. (2013) Biomechanical and Antibacteri-
al Properties of Trobamycin Loaded Hydroxyapatite Coated
Fixation Pins, submitted
VII Lilja M.*, Sörensen J.H.*, Sörensen T., Åstrand M., Procter P.,
Strømme M, Steckel H. (2013) Impact of biomechanical forces
on the release kinetics of hydroxyapatite coated fixation pins, J
Biomater Nanobiotech, 4(4):343-50

*Authors contributed equally to the work.
Reprints were made with permission from the respective publishers.
Author’s Contributions
My contributions to the papers in this thesis were:
Paper I. I was responsible for planning and execution of the studies as well
as writing the manuscript.

Paper II. I took part in the planning and was responsible for sample prepara-
tion and material characterization. I was responsible for writing the manu-
script.

Paper III. I was responsible for planning the study, took part in the experi-
mental work and wrote the manuscript.

Paper IV and V. I took part in the planning of the studies and was responsi-
ble for sample preparation and characterization, except for the HPLC analy-
sis, which was performed by Jan H. Sörensen. Jan Andersson assisted with
GDOES analysis. I was responsible for writing manuscript IV and contribut-
ed to the writing of manuscript V.

Paper VI. I took part in the planning and execution of the experiments, ex-
cept the HPLC analysis, cell study and scratch testing, which were per-
formed by Jan H. Sörensen, Sabine Fuchs and Mikael Fallqvist, respectively.
I was responsible for most of the writing of the manuscript.

Paper VII. I took part in the planning and experimental work of this study,
except for the HPLC analysis, which was performed by Jan H. Sörensen. I
was responsible for writing the manuscript.
Other Publications by the Author:
Journal articles:

• Gebhardt, T., Hajas, D.E., Scholz, M., Hallstedt, B., Cappi, B.,
Song, J., Telle, R., Schneider, J.M (2009) Strength degradation of
NiAl coated sapphire fibres with a V AlC interlayer. Mater Sci
2
Eng A 525(1-2):200-206

• Hajas D.E., Scholz, M., Ershov S., Hallstedt B., Palmquist J.P.,
Schneider J.M. (2010) Thermal and chemical stability of Cr AlC
2
in contact with α-Al O and NiAl. Inter J Mater Res
2 3
101(12):1519-1523

• Lilja, M., Genvad A., Åstrand M., Strømme M, Engqvist H.
(2011) Influence of microstructure and chemical composition of
sputter deposited TiO thin films on in vitro bioactivity, J Mater
2
Sci: Mater Med 22(12):2727–2734

• Lilja M., Welch K., Åstrand M., Engqvist H., Strømme M. (2012)
Photocatalytic and bioactive TiO thin films deposited by vaccum
2
arc, European Cells and Materials, 23;5;48

• Forsgren F., Lilja M., Welch K., Åstrand M., Engqvist H.,
Strømme M. (2012) Photocatalytic and antimicrobial properties of
a TiO implant coating deposited through cathodic arc evapora-
2
tion, European Cells and Materials, 23;5;36

• Lilja M., Umer R. Butt, Shen Z., Bjöörn D. (2013) Nucleation and
growth of hydroxyapatite on arc-deposited TiO coatings studied
2
by quartz crystal microbalance with dissipation, Appl Surf Sci,
284(1):1-6

• Lilja M., Sörensen J.H., Brohede U., Åstrand M., Procter P., Ar-
nolid J., Steckel H., Strømme M. Drug eluting hydroxyapatite
coatings for biomedical applications, European Cells and Materi-
als, 26;2:36
Conference Contributions:

• Lilja, M., Genvad A., Åstrand M., Strømme M, Engqvist H. TiO
2
thin films for biomedical applications by means of physical vapor
deposition, Poster presentation at Euro Bio-inspired Materials, In-
ternational School and Conference on Biological Materials Sci-
ence, Jena, Germany, 13-14 April 2011

• Lilja M., Welch K., Åstrand M., Engqvist H., Strømme M. Bioac-
tive and photocatalytically active surgical implant surfaces, Poster
presentation at Euro Bio-inspired Materials, International School
and Conference on Biological Materials Science, Potsdam, Ger-
many, 20-23 March 2012

• Lilja M., Welch K., Åstrand M., Engqvist H., Strømme M. Photo-
catalytic and bioactive TiO thin films deposited by vaccum arc,
2
Poster presentation at Scandinavian Society for Biomaterials,
Uppsala, Sweden, 8-9 May 2012

• Forsgren J., Lilja M., Åstrand M., Strømme M., Engqvist H.,
Welch K. Photocatalytic and antimicrobial properties of a TiO
2
implant coating deposited through cathodic arc evaporation. Post-
er presentation at Scandinavian Society for Biomaterials, Uppsala,
Sweden, 8-9 May 2012

• Lilja M., Sörensen J.H., Brohede U., Åstrand M., Procter P., Ar-
nolid J., Steckel H., Strømme M. Drug eluting hydroxyapatite
coatings for biomedical applications. Oral presentation at Scandi-
navian Society for Biomaterials, Hafjell, Norway, March 13-15
2013