Transcript Project Overview

Multifunctional bioresorbable
biocompatible coatings with biofilm
inhibition and optimal implant fixation
Project Presentation
LEMI
Content
• Aims
• Approach
• Problem statement & expected breakthroughs
• Envisaged radical innovations
• Scientific & technological objectives
• The Meddelcoat consortium
• Project structure & co-operation
• Project work plan
• Project milestones
• Expected impact
• Administrative information & contact
Project Presentation
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Aims of the MEDDELCOAT project
To develop the next generations of multifunctional
bioactive biocompatible coatings with biofilm inhibition and
optimal implant fixation, eliminating the currently
experienced need for implant revisions due to implant
loosening and infections.
Project Presentation
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Approach of the MEDDELCOAT project
Combinatorial approach
•
•
•
Design and engineer the structure of the implant
surface
to
optimise
implant
fixation
by
osteointegration,
Promote osteointegration by the application of a
bioactive top coating,
Incorporate a biofilm formation inhibiting function
into the coating.
Project Presentation
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Problem statement & expected breakthroughs
State-ofthe-Art
Biomaterial
Biocoatings
Problems
How is this tackled in
MEDDELCOAT
Breakthroughs
expected
Ti or Ti6Al4V
substrates
Limited
biocompatibilit
y of Ti6Al4V,
to secure
implant fixation
until bone
apposition
Implant surface
structuring or the
application of a designed
Ti mesh on the implant
surface to secure implant
fixation by
osteointegration &
development of new
substrate materials
New substrate
materials,
design coatings for
fixation by
osteointegration
Plasma
sprayed Ti,
HA or Ti +
HA
too low coating
adhesion
strength
resulting in
delamination,
additional cost
Design and application of
new bioactive and
resorbable top coatings
with graded interfaces
and tailored porosity on
the structured implant
surface.
Tailored coatings
with enhanced
adhesion strength,
mechanical fixation
and an engineered
stress distribution
Project Presentation
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Problem statement & expected breakthroughs
Biofilm
inhibition
Orthopeadic
&
dental
Implants
State-of-theArt
Problems
How is this tackled
in MEDDELCOAT
Expected
breakthroughs
Limited to bone
cement
impregnated
with antibiotics
The use of
bone cement
and limited
controlled
release
possibility
Investigation of
bacteria-material
interactions. Selection,
incorporation and
evaluation of biofilm
inhibitors.
Biofilm inhibiting
coatings or
coatings with
incorporated
antimicrobial
releasing carriers
Multifunctional
bioresorbable coating
with biofilm inhibition
Prolonged implant
life time
(> 25 %),
reduced need for
revision surgery,
reduced infection
rate
10-20 %
revisions after
15-20 years for
orthopaedic
implants
15 % revisions
for dental
implants after 5
years
Aseptic
loosening,
implant
dislocation,
and bacterial
infection
Project Presentation
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Envisaged radical innovations and major breakthroughs
 Development of new substrate and coating materials with enhanced
biocompatibility.
 Development of radically new or improvement of existing coating
techniques for the processing of bioactive and biocompatible
coatings with a graded interface (adhesion strength) and tailored
porosity (bone in-growth).
 In-depth understanding of the implant substrate/coating/bone
interfacial structure, the design, engineering and control for optimal
implant fixation.
 Novel knowledge on interactions between new coating materials and
bacteria and effective biofilm avoidance/elimination routes
 Evaluation of new biofilm inhibiting substances
 A formulation for the incorporation of anti-infective substances into
the coating
Project Presentation
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Scientific & technological objectives
No
Description
O1
The design and manufacturing of state-of-the-art dental, shoulder (glenoid and humeral bodies) and hip
(stem and acetabular cup) implants suitable for the envisaged coating procedures. New substrates, such as
nanostructured titanium-based alloys, will be developed and evaluated, aiming at a better biocompatibility
compared to standard Ti6Al4V. The targeted E-modulus and fatigue strength of the new substrate material
are respectively 100-120 GPa and 550 MPa.
O2
The development of bioactive glass (BAG), calcium phosphate and titania based precursors or powders for
the processing of new bioactive coatings. The long-term fixation mechanism for the implant will be
established by surface structuring or the deposition of porous Ti as an intermediate coating.
O3
Define guidelines for the microstructural, compositional, morphological and mechanical requirements for
bioactive coatings with improved mechanical fixation (static coating adhesion strength > 40 MPa) and
biofilm inhibiting functionality. Definition of the selection criteria for the coating/substrate systems to be
tested in vivo.
O4
To investigate the possibility to use state-of-the-art techniques such as plasma spraying to engineer the
substrate-coating-bone interface in such a way to realise optimal implant fixation in combination with an
additional bioactivity and biofilm inhibiting functionality. Nanocoatings deposited by combined metal and
bioactive powder spraying will be investigated.
O5
The development of coating techniques which are radically new for implants such as electrophoretic
deposition, selective laser sintering and structuring, dip-coating, plasma enhanced chemical vapour
deposition and laser assisted microwave processing that would allow to engineer the substrate-coatingbone interface in such a way to realise optimal implant fixation in combination with osteointegration and
biofilm inhibiting functionality.
Project Presentation
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Scientific & technological objectives
No
Description
O6
Microstructural characterisation of the BAG, calcium phosphate and titania based advanced
multi-functional substrate-coating systems.
O7
Mechanical characterisation of the BAG, calcium phosphate and titania based advanced
multi-functional substrate-coating systems. The targeted adhesion strength is > 20 MPa for
calcium phosphates and BAG, and > 40 MPa for porous Ti. The targeted adhesion strength
for the multifunctional coating is 30 MPa
O8
Modelling of thermal residual stresses, thermal treatments and material stability to assist
coating design and engineering.
O9
Study the importance of the composition and physicochemical properties of various
substrate-coating systems produced by partners in the consortium on biofilm formation.
Model micro-organism systems which closely simulate the in vivo or in situ conditions for
each device will be used.
O10
To investigate and select the most suitable anti-microbial substances active during a
reasonable and optimal period to reduce infection and biofilm formation to a minimum, and to
investigate the impregnation and release of these selected anti-infectives from the new
substrate-coating biomaterial systems in vitro.
Project Presentation
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Scientific & technological objectives
No
Description
O11
The best anti-infective/biomaterial combination will be tested in the Fisher rat model to
confirm the in vitro results to validate the biofilm reactor approach by means of in vivo
studies carried out using a unique ex-germ-free Fisher rat model.
O12
Biocompatibility testing of cell cultures of powders, abrasion debris and substrate/coating
systems to study the cytotoxicity of raw materials in an early stage of the project, and to
evaluate the various substrate/coating systems and their abrasion debris to determine which
are most relevant for bone regeneration and repair in order to select the most promising
systems.
O13
In vitro bioactivity testing of coating/substrate systems to investigate the bioactivity and
bioresorbability of the various coating-substrate systems with and without antibacterial
substance, in order to evaluate their osteogenic potential and select the most promising
systems for in vivo testing.
O14
In vivo testing of bone bonding of the multifunctional coating/substrate systems using an
adult rabbit model
O15
Feasibility study of the upscaling of the coating technologies for the coating of implants
Project Presentation
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MEDDELCOAT consortium
LEMI
Project Presentation
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LIMA,
LIMA,
HeliPro,
Helipro,
AALTO
KUL-MTM,
KUL ALHENIA, UoB
ALHENIA, AMES,
Coating
Coating
and
and
sintering
sintering
technology
technology
(WP2) Alhenia, AMES,
KUL-MTM,UoB,
UoB,IJS
IJS
KUL-MTM,
Characterisation
Characterisation
and
and
evaluation
evaluation
(WP2)
IMMG, KUL-MTM,
UoB, IJS
LIMA, AALTO,
Modelling
Modelling
and finite element analysis
LIMA,(WP2)
HUT, KUL-MTM, UoB
KUL-MTM, UoB
Bacteria-material interaction (WP3)
KUL-REGA,
KUL-REGA,
OctoPlus
HEMOTEQ
LEMI,IJS,
HeliPro,
IJS,
Biocompatibility
Biocompatibility
testing
testing
(WP4)LEMI, Helipro,
KUL-MTM
KUL-MTM
Upscaling feasibility (WP5)
(WP7)
all partners
partners)
Training activities (all
Substrates
&&
powders
(WP1)
Substrates
powders
Selection of implants (LIMA,
(WP1) (LIMA,
Helipro)Heli Pro)
partners)
(allpartners
& Engineering
& Engineering
design design
Coating
Coating
(WP2) all
Demonstration
activities (WP8) all
Innovation-related
activities (WP6) all
RTD-activities
(WP1-WP5) all
Project structure & partner co-operation
all partners
Dissemination and
exploitation (all partners)
Project Presentation
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Project work plan overview
WP 3: Bacteria-coating
interaction
Task 3.1: Bacteria-coating
interaction investigation
WP 2: Coating of implants
WP 1: Substrates &
bioactive powders
Task 2.3: Bioresorbable and bioactive
coatings
Task 2.4: Thermal treatments
Task 1.1: Selection & supply of
substrates and implants
Task 1.2: Selection & supply of
bioactive powders
Task 2.5: Structural characterisation
of coating/substrate systems
Task 2.6: Mechanical
characterisation of coating/substrate
systems
Task 2.7: Modelling and finite
element analysis & thermodynamic
and kinetic modelling
Task 2.1: Coating engineering & design
Task 2.2: Coatings for implant
fixation
Task 3.2: Selection and
incorporation of biofilm inhibitors
Task 3.3: Evaluation of biofilm
inhibiting coatings
WP 4: Biocompatibility and
activity testing
Task 4.1: Cell culture of powders
and coated implants
Task 4.2: Bioactivity and
resorbability testing of coatings
WP 5: Upscaling feasibility
WP 6: Innovation related activities
WP 7: Demonstration activities
WP 8: Training activities
WP 9: Project management
Project Presentation
Task 4.3: In-vivo testing of bone
bonding
13
Project milestones
No
Month
M0
0
Signed Consortium Agreement (All Partners)
M1
18
Supply of state-of-the-art dental and shoulder implants and hip stems and
acetabular cups (HeliPro, LIMA)
M2
12
Development and supply of a range of bioactive powders (Alhenia, KUL-MTM,
UoB)
M3
6
Initial composition definition of the graded Ti metal/bioactive material coating (All
Partners)
M4
6
State-of-the-art vacuum plasma sprayed calcium phosphate and Ti + HA coatings
as a reference for biofilm formation investigation (WP 3), coating adhesion testing
and biocompatibility and activity investigation (Alhenia)
M5
18
Supply of the first multi-functional (fixation + bioactive) substrate-coating
combination (KUL-MTM, IJS, UoB, Alhenia)
M6
24
Supply of the first generation of multi-functional (fixation + bioactive) substratecoating combination for each processing route (KUL-MTM, IJS, UoB, Alhenia)
24
Microstructural characterisation of the vacuum plasma sprayed state-of-the-art
coatings and the first advanced multi-functional substrate-coating systems (IJS,
KUL-MTM, UoB).
M7
Description
Project Presentation
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Project milestones
No
Month
Description
M8
30
Nanoscale microstructural characterisation of the vacuum plasma sprayed stateof-the-art coatings and the first generation of advanced multi-functional substratecoating systems (IJS).
M9
24
Mechanical characterisation of the first generations of advanced multi-functional
substrate-coating systems (IMMG).
18
Micromechanical and finite element model for the evaluation of the thermal
residual stresses and thermal treatments of the envisaged substrate/coating
systems. (AALTO)
M11
24
Assessment of the physicochemical properties of biomaterials which limit the
adherence of micro-organisms to the substrate, and hence, will avoid biofilm
formation. (KUL-REGA)
M12
24
Knowledge on the best anti-infective/biomaterial combination and formulation for
an efficient prophylactic and therapeutic action (KUL-REGA, HEMOTEQ)
M13
36
Biofilm inhibitor formulation (HEMOTEQ)
M14
45
Biofilm inhibiting coatings evaluated in vivo. (KUL-REGA)
M15
18
Evaluation of cytotoxicity testing of bioactive starting powders and substrates
(LEMI)
M10
Project Presentation
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Project milestones
No
Month
Description
M16
30
Evaluation of cytotoxicity testing of the new coating-substrate systems (LEMI)
M17
36
Biocompatibility evaluation of the abrasion wear debris generated in the pin-onflat tests (LEMI)
M18
24
In vitro bioactivity evaluation of state-of-the-art vacuum plasma sprayed and the
first generations of multi-functional coating/substrate systems (LEMI, KUL-MTM).
M19
36
Evaluation of bioactivity testing of the substrate/coating systems (LEMI, KULMTM)
M20
45
Evaluation of bone bonding of the multifunctional substrate/coating systems (HeliPro, IJS, KUL-MTM)
M21
45
Feasibility study for a continuous microwave heating system for the coating of
implants with different geometries (AMES)
M22
42
Feasibility study for the upscaling of the coating processing routes for implants
with different geometry (KUL-MTM, IJS, UoB, Alhenia)
M23
24
Critical progress review milestone (all partners)
M24
36
Selection of the multifunctional substrate/coating systems for in vivo bone
bonding testing (all Partners).
Project Presentation
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Expected impact of the MEDDELCOAT project
• Community societal objectives
– The project aims at a drastic decrease of implant failures,
concomitantly reducing the number of revisions, lowering the pain
and suffer of the patients and decreasing the medical costs for
patients and community.
– The implementation of highly reliable implants definitely improves
the mobility and quality of live of those among us who need it
because of age, illness or accident.
– SME-driven market ! Small and medium size companies together
make up more than 80 % of medical technology business entities.
This industry contributes significantly to saving life and improving
the quality of life of the citizens of Europe.
– SMEs are the main job creators of European industry.
MEDDELCOAT will enhance the ability of the SMEs involved to
improve their competitiveness, with an immediately positive effect
in job creation.
Project Presentation
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Expected impact of the MEDDELCOAT project
• Contribution to policy developments
– The project addresses the integration of nanotechnologies, material
science and advanced technologies to improve health and quality of
life of European citizens and creating wealth through novel
knowledge-based and sustainable products (biomaterials) and
processes (coatings).
– The project will contribute to a dynamic and competitive knowledgebased economy (“Lisbon” objective), sustainable development
(“Göteborg” objective), and serves the needs of a traditional SMEintensive industrial sector.
– The project contributes to the ERA by focussing on
nanotechnologies, intelligent materials and new production
processes; sustainable development; genomics and biotechnology
for health; and citizens and governance in the European knowledgebased society (4 of the 7 research priorities for Europe) and
especially enhances the participation of SMEs in ERA.
Project Presentation
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Expected impact of the MEDDELCOAT project
– Biomedical implants are knowledge-based products with high
added value. At present, about 60 % of the implant market in
Europe is controlled by non-EU companies. The development of a
technology, as envisaged in the IP-SME project, would give
competitive advantage to European SMEs which is of high interest
not only to conserve employment, but also to create new jobs in
Europe.
– The proposed research is of strategic importance to the EU in view
of the massive impact on market share which would result from the
development of the envisaged biomaterials with multifunctional
bioresorbable biocompatible coatings with biofilm inhibition and
optimal implant fixation.
Project Presentation
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Expected impact of the MEDDELCOAT project
• Gender issues
– The goal within this project is to reach a minimum of 25 %
of female researchers at the recruitment stage and
encourage greater participation at senior level, which is
significantly higher than the European average of 15 %
for industrial research.
• Contribution to standards
– The activities related to the bacteria-material interaction
investigation, the development and evaluation of coating
integrated biofilm inhibitors, and biocompatibility testing
will result in an active participation in European and
international standardisation committees.
Project Presentation
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Expected impact of the MEDDELCOAT project
• Economic impact
– The $80B medical device industry continues to grow at 9 % per year,
driven by the aging global population and medical advances.
– Less than 5 % of the medical device market now utilizes surface
modification technology of any kind. As the demand for better, more
advanced biomaterials accelerates in step with scientific
breakthroughs, the market for surface modification of existing
medical devices is expected to grow at approximately 80-90% per
year for the next 5 years, as the market adopts "intelligent" coatings.
– Early adopters will use the coatings to either improve device
biocompatibility or reduce infection; later generations of coatings
could conceivably employ a nearly infinite array of therapeutic
agents. We anticipate that "intelligent" coatings for medical devices
and biologic implants will become the standard of care.
Project Presentation
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Administrative information
• Project
– Type: IP-SME
– Contract no.: NMP3-CT-2006-02651
– www.meddelcoat.eu
• Project duration: 01/10/2006 – 31/3/2011
• No. of person-months: 674
• Budget:
– Total project budget: 4706 k€
– EC funding: 3300 k€
• Project co-ordination: K.U.Leuven R&D (Leuven, Belgium)
Project Presentation
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Contact
• For further information
– Visit: www.meddelcoat.eu
– Project coordinator:
Prof. Dr. ir. Jef Vleugels
Katholieke Universiteit Leuven
Departement of Metallurgy and Materials Engineering (MTM)
Kasteelpark Arenberg 44, B-3001 Heverlee (Belgium)
phone: +32-16-321244, fax: +32-16-321992
E-mail: [email protected]
LEMI
Project Presentation
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