uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Bioactive Surgical Implant Coatings with Optional Antibacterial Function
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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 TiO2 and biomimetic hydroxyapatite (HA) coatings were evaluated with respect to their potential as antibacterial surface modifications for bone-anchored implants.

UV light induced photocatalysis of anatase dominated TiO2 coated surfaces was shown to 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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 60 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1091
Keyword [en]
Hydroxyapatite, titanium dioxide, photocatalysis, antibacterial effect, antibiotic release, biomimetic coating, co-precipitation, tobramycin
National Category
Medical Materials Materials Engineering
Identifiers
URN: urn:nbn:se:uu:diva-209283ISBN: 978-91-554-8782-9 (print)OAI: oai:DiVA.org:uu-209283DiVA: diva2:656612
Public defence
2013-12-05, Room Å2001, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2013-11-13 Created: 2013-10-16 Last updated: 2014-01-23
List of papers
1. Effect of deposition parameters on the photocatalytic activity and bioactivity of TiO(2) thin films deposited by vacuum arc on Ti-6Al-4V substrates
Open this publication in new window or tab >>Effect of deposition parameters on the photocatalytic activity and bioactivity of TiO(2) thin films deposited by vacuum arc on Ti-6Al-4V substrates
Show others...
2012 (English)In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 100B, no 4, 1078-1085 p.Article in journal (Refereed) Published
Abstract [en]

This article evaluates the influence of the main parameters in a cathodic arc deposition process on the microstructure of titanium dioxide thin coatings and correlates these to the photocatalytic activity (PCA) and in vitro bioactivity of the coatings. Bioactivity of all as deposited coatings was confirmed by the growth of uniform layers of hydroxyapatite (HA) after 7 days in phosphate buffered saline at 37°C. Comparison of the HA growth after 24 h indicated enhanced HA formation on coatings with small titanium dioxide grains of rutile and anatase phase. The results from the PCA studies showed that coatings containing a mixed microstructure of both anatase and rutile phases, with small grain sizes in the range of 26-30 nm and with a coating thickness of about 250 nm, exhibited enhanced activity as compared with other microstructures and higher coating thickness. The results of this study should be valuable for the development of new bioactive implant coatings with photocatalytically induced on-demand antibacterial properties.

Keyword
bioactive material, crystallinity, implant design, implant interface, in vitro
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials; Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-172590 (URN)10.1002/jbm.b.32674 (DOI)000302402700022 ()22447517 (PubMedID)
Available from: 2012-06-26 Created: 2012-04-12 Last updated: 2017-12-07Bibliographically approved
2. Photocatalytic and antimicrobial properties of surgical implant coatings of titanium dioxide deposited though cathodic arc evaporation
Open this publication in new window or tab >>Photocatalytic and antimicrobial properties of surgical implant coatings of titanium dioxide deposited though cathodic arc evaporation
Show others...
2012 (English)In: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 41, no 6, 740-746 p.Article in journal (Refereed) Published
Abstract [en]

Nanostructured crystalline titaniumdioxide coatings deposited by cathodic arc evaporated on titanium grade five medical implant substrates were demonstrated to exhibit UV-induced photocatalytic activity that can be utilized to provide bactericidal effects against Staphylococcus epidermidis. The photocatalytic activity of the coatings was confirmedvia degradation of Rhodamine B under UV illumination.A 90 %reduction of viable bacteria was achieved in a clinically suitable time of only 2 min with a UVdose of 2.4 J delivered at 365 nm. These results areencouraging for the development of antimicrobialsurfaces in orthopedics and dentistry in order to prevent or treat post-surgical infections.

National Category
Materials Engineering
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials; Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-181780 (URN)10.1007/s10529-012-1040-2 (DOI)000310587500021 ()
Available from: 2012-09-28 Created: 2012-09-28 Last updated: 2017-12-07Bibliographically approved
3. The effect of Si-doping on the release of antibiotic from hydroxyapatite coatings
Open this publication in new window or tab >>The effect of Si-doping on the release of antibiotic from hydroxyapatite coatings
Show others...
2013 (English)In: Journal of Biomaterials and Nanobiotechnology, ISSN 2158-7027, E-ISSN 2158-7043, Vol. 4, no 3, 237-241 p.Article in journal (Refereed) Published
Abstract [en]

Herein, we show that incorporation of ions during biomimetic coating deposition may be utilized to tailor the drug loading capacity of hydroxyapatite (HA) coatings. Pure biomimetic HA (HA-B) and Si-doped equivalents (SiHA-B) where deposited by a biomimetic process onto titanium dioxide covered titanium substrates. The antibiotic Cephalothin was incorporated into the coatings by adsorptive loading and the release was studied in-vitro. SiHA-B coatings exhibited superior drug incorporation capacity compared to pure HA-B coatings, resulting in a drug release profile dominated by an initial 10 min burst effect while a more prolonged 10 hour release was observed from HA-B coatings. The results emphasize the possibility to impact the drug release kinetics from implant coatings by selective doping elements and the use of thin, biomimetic HA-coatings as drug delivery vehicles. Functionalizing metal implants with SiHA-B coatings presents an interesting strategy towards creating synergetic effects through ion- and antibiotic release and, hence, contributing both towards preventing post-surgical infections while at the same time enhancing the bone-bonding ability.

Keyword
Titanium Dioxide, Hydroxyapatite, Cephalothin, Drug Release, Si-Doping
National Category
Medical Materials
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials; Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-203447 (URN)10.4236/jbnb.2013.43029 (DOI)
Available from: 2013-07-10 Created: 2013-07-10 Last updated: 2017-12-06Bibliographically approved
4. Drug loading and release of Tobramycin from Hydroxyapatite coated fixation pins
Open this publication in new window or tab >>Drug loading and release of Tobramycin from Hydroxyapatite coated fixation pins
Show others...
2013 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 24, no 9, 2265-2274 p.Article in journal (Refereed) Published
Abstract [en]

This paper evaluates the loading and release properties of Tobramycin incorporated by adsorptive loading from a solution into plasma sprayed and biomimetically coated Hydroxyapatite (HA) fixation pins. The aim of this study is to contribute towards designing a functional implant surface offering local release of the antibiotic agent to prevent post-surgical infections. Cathodic arc deposition is used to coat stainless steel fixation pins with a bioactive, anatase phase dominated, TiO2 coating onto which a HA layer is grown biomimetically. The loading and release properties are evaluated by studying the subsequent release of Tobramycin using high performance liquid chromatography and correlated to the differences in HA coating microstructure and the physical conditions under loading. The results from these studies show that a dual loading strategy consisting of a solution temperature of 90 °C and a pressure of 6 bar during a loading time of 5 min release a sufficient amount of Tobramycin to guarantee the inhibition of Staphylococcus aureus up to 2 days for plasma sprayed HA coatings and for 8 days for biomimetic coatings. The present study emphasizes the advantages of the nanoporous structure of biomimetically deposited HA over the more dense structure of plasma sprayed HA coatings in terms of antibiotic incorporation and subsequent sustained release and provides a valuable outline for the design of implant surfaces aiming for a fast-loading and controlled, local drug administration.

National Category
Medical Materials
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-203448 (URN)10.1007/s10856-013-4979-1 (DOI)000323289600018 ()
Available from: 2013-07-10 Created: 2013-07-10 Last updated: 2017-12-06Bibliographically approved
5. Co-precipitation of Tobramycin into Hydroxyapatite Coatings
Open this publication in new window or tab >>Co-precipitation of Tobramycin into Hydroxyapatite Coatings
Show others...
(English)Article in journal (Refereed) Submitted
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-209042 (URN)
Available from: 2013-10-14 Created: 2013-10-14 Last updated: 2014-01-23Bibliographically approved
6. Biomechanical and Antibacterial Properties of Tobramycin Loaded Hydroxyapatite Coated Fixation Pins
Open this publication in new window or tab >>Biomechanical and Antibacterial Properties of Tobramycin Loaded Hydroxyapatite Coated Fixation Pins
Show others...
2014 (English)In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 102, no 7, 1381-1392 p.Article in journal (Refereed) Published
Abstract [en]

The present study investigates the use of nanoporous, biomimetic hydroxyapatite (HA) coatings deposited on TiO2 coated fixation pins as functional implant surfaces for the local release of Tobramycin in order to prevent bacterial colonization. The impact of HA-coating thickness, coating morphology and biomechanical forces during insertion into synthetic bone on the drug loading and release properties are analyzed. The coatings are shown to exhibit bactericidal effects against Staphylococcus aureus in agar medium for a duration of 6 days after loading by adsorption with Tobramycin for only 5 min at elevated temperature and pressure. Furthermore, high performance liquid chromatography analysis shows a drug release in phosphate buffered saline for 8 days with antibiotic concentration remaining above the minimal inhibitory concentration for S. aureus during the entire release period. Biomechanical insertion tests into synthetic bone and conventional scratch testing demonstrate adhesive strength at the HA/TiO2 interface. Biocompatibility is verified by cell viability tests. Outgrowth endothelial cells, as well as primary osteoblasts, are viable and firmly attached to both HA and TiO2 surfaces. The results presented are encouraging and support the concept of functional HA coatings as local drug delivery vehicles for biomedical applications to treat as well as to prevent post-surgical infections.

National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-209043 (URN)10.1002/jbm.b.33117 (DOI)000342963000003 ()
Funder
Swedish Research Council
Available from: 2013-10-14 Created: 2013-10-14 Last updated: 2017-12-06Bibliographically approved
7. Impact of Biomechanical Forces on Antibiotics Release Kinetics from Hydroxyapatite Coated Surgical Fixation Pins
Open this publication in new window or tab >>Impact of Biomechanical Forces on Antibiotics Release Kinetics from Hydroxyapatite Coated Surgical Fixation Pins
Show others...
2013 (English)In: Journal of Biomaterials and Nanobiotechnology, ISSN 2158-7027, E-ISSN 2158-7043, Vol. 4, no 4, 343-350 p.Article in journal (Refereed) Published
Abstract [en]

This work investigates the impact of biomechanical wear and abrasion on the antibiotic release profiles of hydroxyapa-tite (HA) coated fixation pins during their insertion into synthetic bone. Stainless steel fixation pins are coated with crystalline TiO2 by cathodic arc evaporation forming the bioactive layer for biomimetic deposition of Tobramycin con-taining HA. Tobramycin is either introduced by co-precipitation during HA formation or by adsorption-loading after HA deposition. The samples containing antibiotics are inserted into bone mimicking polyethylene foam after which the drug release is monitored using high performance liquid chromatography. This analysis shows that HA coating wear and delamination significantly decrease the amount of drug released during initial burst, but only marginally influence the sustained release period. Spalled coating fragments are found to remain within the synthetic bone material structure. The presence of HA within this structure supports the assumption that the local release of Tobramycin is not only ex-pected to eliminate bacteria growth directly at the pin interface but as well at some distance from the implant. Further-more, no negative effect of gamma sterilization could be observed on the drug release profile. Overall, the observed results demonstrate the feasibility of a multifunctional implant coating that is simultaneously able to locally deliver clinically relevant doses of antibiotics and an HA coating capable of promoting osteoconduction. This is a potentially promising step toward orthopaedic devices that combine good fixation with the ability to treat and prevent post-surgical infections.

National Category
Medical Materials
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-208513 (URN)10.4236/jbnb.2013.44043 (DOI)
Available from: 2013-10-02 Created: 2013-10-02 Last updated: 2017-12-06Bibliographically approved

Open Access in DiVA

fulltext(30662 kB)1177 downloads
File information
File name FULLTEXT01.pdfFile size 30662 kBChecksum SHA-512
054901a5d93e39b0f5da94ef9554344a5f8fd706c0d1336df6712d31d026b2cd621b6af3832eec919b1dec6d5d6a091a13c3d6ba1cad02495926b45fd7ee7958
Type fulltextMimetype application/pdf
Buy this publication >>

By organisation
Nanotechnology and Functional Materials
Medical MaterialsMaterials Engineering

Search outside of DiVA

GoogleGoogle Scholar
Total: 1177 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1455 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf