Biologically Functionalised Sol-gel Coatings
Submitting Institution
Sheffield Hallam UniversityUnit of Assessment
Biological SciencesSummary Impact Type
TechnologicalResearch Subject Area(s)
Chemical Sciences: Analytical Chemistry, Macromolecular and Materials Chemistry
Engineering: Biomedical Engineering
Summary of the impact
Interdisciplinary work by microbiologist Smith TJ and materials
science collaborators has led to (i) the development of novel
environmentally friendly coatings for anti-corrosion and anti-biofouling
applications that have attracted attention across diverse industries; (ii)
the development of a platform technology that includes an antimicrobial
coating currently under investigation for use on orthopaedic prostheses
and (iii) associated work quantifying elution of antibiotics from
orthopaedic cement in clinical use. The research has been disseminated via
journal publications and patents have been obtained. Impact is evidenced
by commercial interest, which has led to collaborative field trials under
an EPSRC follow-on fund grant and contract research and consultancy funded
by industry and the NHS.
Underpinning research
Smith TJ was appointed by Sheffield Hallam University (SHU) in
2001 as Senior Lecturer in Microbiology (Professor of Microbiology,
2011-present). His expertise in bacterial monooxygenases (e.g. reference
1) underpinned a successful Biotechnology and Biological Research Council
(BBSRC) New Investigator grant in 2002 (grant 1). His research track
record includes applied microbiology, enzymology and characterisation of
bacterial endospores (grants 2- 4). In 2005, Smith TJ was funded
by SHU's Promising Researcher Fellowship Scheme (£49,964) to undertake
full time research. During this period, Smith TJ and Akid
(Materials and Engineering Research Institute at SHU 1999-2012, University
of Manchester since March 2012) initiated a collaboration combining
Smith's expertise in microbiology with Akid's expertise in materials
science to develop functionalised coatings with wide ranging potential
applications. The original coating concept, supported by a "Yorkshire
Concept" grant from the Regional Development Agency (grant 5), combined a
robust sol-gel coating with immobilised bacterial endospores to produce a
biological anti-corrosion coating. We demonstrated that the coating was
effective against corrosion of aluminium alloy in the laboratory and
during a six-month field trial in the estuarine environment at the Thames
Barrier, conducted in collaboration with the Environment Agency (reference
2).
Use of immobilised bacteria is superior to other functionalised coatings
in that bacterial growth has the capacity to replenish the active agent,
and the sol-gel coating offers a physically more robust matrix for
long-term immobilisation than softer hydrogels. Smith TJ's insight
as a microbiologist enabled a critical improvement, which involved
immobilising the bacteria in the form of endospores, the most resistant
life-form known, which can withstand the harsh conditions imposed during
coating curing. Smith TJ performed all microbiology laboratory
work leading to reference 2.
Further development of the functionalised sol-gel coating led to coatings
with anti-fouling activities that resist colonisation by barnacles and
other fouling organisms in the marine environment (grant 6). The team
subsequently obtained an Engineering and Physical Sciences Research
Council (EPSRC) Follow-on Fund grant to drive the technology towards
market and to establish commercial collaborations (grant 7); this has
included a collaboration, incorporating field trials, with International
Paint.
Seed-corn funding to Smith TJ via an EPSRC Bridging the Gap grant
(EP/H000275) held by SHU in addition to a Regional Development Agency
Fellowship to collaborator Akid (whilst still at SHU) enabled Smith TJ
to produce a derivative coating containing antibiotics, for use as
controlled- release antimicrobial coatings in orthopaedic surgery. The
release kinetics indicated that the coating would give protection during
the critical perioperative period when pathogenic microorganisms can enter
the surgical wound. These encouraging results led to a Medical Research
Council (MRC) Development Pathway Funding Scheme grant (grant 8), with
microbiology and coating development being conducted in the Biomedical
Research Centre at SHU under Smith TJ's supervision and in
vivo trials in rat models by collaborator Hatton at the University
of Sheffield. At the time of writing (10/2013), coatings had been
reformulated to optimise adhesion and release kinetics and are currently
under test in the animal model.
The novel coating technologies have been patented by SHU (Patents 1, 2)
with Smith TJ's lead position in the field having been further
consolidated by a recent comprehensive review article (reference 3). Our
work toward antimicrobial coatings for orthopaedic surgery led local
orthopaedic surgeons and consultant microbiologists to become aware of Smith's
group's expertise and led to a study characterising elution kinetics of
antibiotics from orthopaedic cement (reference 4) that was required in
order to inform clinical practice in orthopaedic surgery. This, in turn,
has resulted in contract research funded by industry and the NHS and
associated knowledge transfer relating to the incorporation of antibiotics
into orthopaedic cement, as detailed in section 4 below.
References to the research
(citations from Scopus 25/10/2013)
1. Borodina, E., Nichol, T., Dumont, M. G., Smith, TJ and
Murrell, J. C. 2007. Mutagenesis of the "leucine gate" to explore the
basis of catalytic versatility in soluble methane monooxygenase. Appl.
Environ. Microbiol. 73, 6460-6467. DOI 10.1128/AEM.00823-07 (9
citations, underpinned successful application for BBSRC grant -
grant no. 3 below).
2. Akid, R., Wang, H., Smith, TJ, Greenfield, D. and
Earthman, J. C. 2008. Biological functionalisation of a sol gel coating
for the mitigation of Microbial Induced Corrosion (MIC). Adv. Functional
Mat. 18, 203-211. (9 citations) DOI
10.1002/adfm.200600493.
3. Gittens, JE, Smith TJ, Suleiman R and Akid R 2013.
Current and emerging environmentally- friendly systems for fouling control
in the marine environment accepted for publication in Biotechnology
Advances. DOI 10.1016/j.biotechadv.2013.09.002.
4. Dodds, S., Smith, TJ, Akid, R., Stephenson, J., Nichol,
T., Banerjee, R.D., Stockley, I. and Townsend, R. 2012. Contrasting
effects of physical wear on elution of two antibiotics from orthopedic
cement. Antimicrob. Ag. Chemoter. 56, 1471-1475. DOI 10.1128/AAC.01588-10.
Patents
1. Wang H, Smith T and Akid R. 2008. Sol Gel Biocote 1,
EP08788766.7. Biological functionalisation of a sol gel coating for the
mitigation of biofouling microbial induced corrosion.
2. Smith T, Wang H, Gittens J, Akid R. 2012. Sol Gel Biocote 2.
GB1221703A.
3. Wang H, Akid R and Smith T. 2007. WO 2010/023483. Sol
Gel Antibiotic. EP2328627A & US13/060859.
Research grants:
(Amounts of funding on collaborative grants are the amounts received by
Sheffield Hallam University. Smith TJ is PI unless stated
otherwise).
1. 2004 - 2007 BBSRC `Laboratory evolution of alkene
monooxygenase for improved chiral synthesis' E20252 £182,933).
2. 2005 - 2007 BBSRC `Exploring the catalytic versatility of
soluble methane monooxygenase' BB/C00399X/1, £108,241 in
collaboration with University of Warwick
3. 2008 - 2011 BBSRC. Novel monooxygenase biocatalysts from
the environment and the laboratory. BB/F01449X/1 £293,905 in
collaboration with University of Warwick
4. 2010-2013 Healthcare Infection Society. (£76,620) Molecular
microbial ecology of hospital ward environments: a new tool to understand
the role of the environment in hospital acquired infections.
5. 2005-2006 Yorkshire Concept `Biocoat: A novel coating
application which combines bio technology with traditional sol gel
coatings as a means of resisting corrosion', £40,000
6. 2009-2011 Akid and TJ Smith EPSRC, 20 07-10,
EP/F008643/1, £355,000. `Development of a functional sol gel coating
system via encapsulation of microorganisms'
7. 2011 -2012 Akid, TJ Smith, Wang, EPSRC (Follow-on
Fund), EP/I028471/1, £ 130,394. `Probiotic, biocide-free antifouling
coatings based upon sol-gel encapsulated micro-organisms'
8. 2012 -2014 (MRC DPFS grant, MR/J014656/1), 2013-5, £170,311. TJ
Smith Co-I, `Controlled release therapeutic coatings for
orthopaedic devices based upon novel sol-gel formulations' in
collaboration with Universities of Manchester and Sheffield.
Details of the impact
Biologically functionalised coatings for mitigation of corrosion and
biofouling
Our biologically functionalised coatings technology has been recognised
as a promising and potentially transformative technology, with diverse
applications in medicine and engineering; this has occurred, through the
initial publication in Advanced Functional Materials (reference 2),
together with national and international presentations made by Smith
TJ and collaborator Akid. Presentations on the anti-corrosion and
anti-fouling technology delivered to audiences with substantial commercial
representation have included: an oral presentation at "Advances in
Corrosion Protection by Organic Coatings" (Cambridge, 2009) (source
6) that was also reported as a paper in ECS transactions, student poster
prizes and associated publicity from conferences at the Materials
Knowledge Transfer Network (London, 2009) (source 7) and Royal Institute
of Structural Engineers (London, 2010) and invited joint oral
presentations by Smith TJ and Akid at two meetings at The
Institute of Materials, Minerals and Mining (Industrial uses of
bacteria and Cleaning up antifouling, both held in London
during 2010) (source 8). In addition, the favourable outcome from the
Yorkshire Concept funded project in showing the feasibility of the
anticorrosion coating in the marine environment, which was publicised via
the funder's website (source 9) and reference 2, led to enquiries from at
least 10 companies during the period 2009-13. Interested companies in the
anti-corrosion and antifouling coatings industry included: International
Paint, (a subsidiary of AkzoNobel N.V., the world's largest coatings
manufacturer), which worked with us under the EPSRC Follow on Fund grant
(2011-12) (grant 7) providing access to its field test facilities (source
1). Given the magnitude of microbial induced corrosion and biofouling
problems, especially in the marine engineering sector as well as other
industries (including transport infrastructure, power industry, etc.),
there is an acute need for non-polluting new coating technology to be
developed further. Together with the need to move away from established
biocide-based technologies, due to increasingly stringent environmental
legislation, this issue has advanced commercial interest in the coating.
Identified beneficiaries include the shipping industry, off-shore power
generation companies with structures in the marine environment, as well as
diverse sectors where the corrosion and fouling of materials in the
environment is a threat (source 2).
Coatings and antibiotics in orthopaedic surgery
Presentations relating to the medical applications of antimicrobial
coatings have included the International Conference on Antimicrobials
Research (oral presentation, Valladolid, Spain, 2010) and the Federation
of Infection Societies (poster, Manchester, 2011), both with substantial
representation from industry and clinical medicine, and also national
meetings for microbiologists, surgeons and device manufacturers with
interests in treating orthopaedic infections held in Sheffield in 2011 and
2012. Following these events, a number of medical device manufacturers
have held meetings with us, under 'confidentiality agreements', on their
interest in the antibiotic sol- gel coating for orthopaedic devices. These
manufacturers include De Puy Orthopaedics (2008), an international device
manufacturer part of the Johnson and Johnson Group, and Biomet UK, an
advanced engineering and manufacturing technology orthopaedic joint
replacement company, Bridgend, Wales. Our funding from MRC precludes any
exclusive relationship with commercial partners. However, we plan to seek
a commercial partner on completion of the current MRC- funded (grant 8).
Collaboration with NHS consultant orthopaedic surgeons at the Sheffield
Teaching Hospitals NHS Foundation Trust (STH NHS FT) (source 3) on the use
of the antimicrobial coatings resulted in further applications of the
coating technology in relation to infection control following joint
replacement operations. In addition, our discussions with orthopaedic
consultants and the work reported in reference 4 have led to industry- and
NHS-funded contract research to provide information about the suitability
of new antibiotics for incorporation into orthopaedic cement to inform
clinical practice and to help combat increasing antibiotic resistance in
the clinical arena. The Sheffield Teaching Hospital Research and
Development Fund supported Smith TJ in delivering two projects in
2012: on `Clinical use and underlying elution characteristics of combined
gentamicin and daptomicin in orthopaedic cement' (value £2,800); and
`Quantifying elution of antibiotics vancomycin and gentamicin from
orthopaedic cement samples; physical strength testing of samples' (value
£3,000). These projects were funded to address specific needs for
knowledge to inform clinical practice in orthopaedic surgery. Information
about the activity and elution of the antibiotics from cement was required
by surgeons and clinical microbiologists to determine which antibiotics
could be used in orthopaedic cement in difficult-to-treat cases of
revision surgery. Source 3, a nationally recognised senior consultant
orthopaedic surgeon, has commented on this work: "Collaborative
research with the BMRC at Sheffield Hallam University evaluating the
elution properties of different antibiotics from acrylic bone cements
has made a significant impact in the management of difficult
periprosthetic joint infections." Results have been communicated to
clinicians in the STH NHS FT and will be submitted to peer reviewed
journals shortly. Through collaboration with clinicians, Smith TJ
secured an introduction to Heraeus (source 4), a manufacturer of
orthopeadic bone cement; this led to Smith TJ advising the company
on measurement of elution rates of antibiotics from bone cement and to our
performing laboratory tests to characterise the elution of antibiotics
from their products. Work this the pharmaceutical manufacturer Eumedica
included supply of the antibiotic temocillin, which together with funding
via a `student into work' grant (£2000) June-August 2012 (from the Society
for Applied Microbiology) allowed us to establish that temocillin remained
active after curing of bone cement and eluted on a timescale that suggests
it would be appropriate for use in surgery. Funding for a larger project
was provided by Pfizer PLC via an Anti-Infectives Research Foundation
grant (2010-11; £46,750) to Smith TJ and Akid in MERI at SHU; this
project investigated the elution of antibiotics linezolid and tigecycline
to assess their suitability for use in orthopaedic cement (source 5).
Further to this, we have engaged in knowledge transfer with the
orthopaedic department of STH NHS FT by training three orthopaedic
registrars (junior clinicians in orthopaedic surgery) in methodology and
theory relating to measurement of antibiotic elution from orthopaedic
cement.
Sources to corroborate the impact
Source 1. Principal Research Technologist, International Paint Ltd
Gateshead.
Source 2. Principal Scientist in physical sciences group on
corrosion and erosion related issues, Defence Science and Technology
Laboratory, Wiltshire.
Source 3. Consultant orthopaedic surgeon, Sheffield Teaching
Hospitals NHS Foundation Trust, Sheffield.
Source 4. Area Manager, Heraeus Medical Division, Newbury.
Source 5. Investigator Initiated Research Manager, Pfizer PLC,
Surrey.
Source 6. Advances in Corrosion Protection by Organic Coatings:
Christ's College, Cambridge 13th-17th September 2009 - 30 minute
presentation and conference paper (Gittens J. E., Wang, H., Smith TJ,
Akid, R. and Greenfield, D. (2009). Biotic sol-gel coating for the
inhibition of corrosion in seawater. ECS transactions, 24
(1), 211-229).
Source 7. Materials for a Safer World - Materials KTN Annual
Meeting 23/04/2009, Church House Conference Centre, London. Overall winner
for poster competition, 'A Novel Biocide-free Approach to the Prevention
of Corrosion and Marine Biofouling'.
https://connect.innovateuk.org/documents/2998699/3675992/Focus+Magazine+Issue+12.pdf/9d33
0c8b-85d5-4446-b8b3-eab5d53661be
Source 8. Marine Corrosion Forum, Technical Presentations at the
July 2010 Meeting http://www.marinecorrosionforum.org/tpjul10.htm
Source 9. http://www.yorkshireconcept.org/downloads/Case%20Studies/CP5274%20-
%20YC_A0%20Poster_Ref%2006_Mitigation_Sheffield_V3.pdf