multifunctional bioresorbable biocompatible coatings with biofilm inhibition and optimal implant...
TRANSCRIPT
Multifunctional bioresorbable biocompatible coatings with biofilm
inhibition and optimal implant fixation
LEMI
Project Presentation
2Project Presentation
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
3Project Presentation
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.
4Project Presentation
Approach of the MEDDELCOAT project
• 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.
Combinatorial approach
5Project Presentation
Problem statement & expected breakthroughs
State-of-the-Art
ProblemsHow is this tackled in
MEDDELCOATBreakthroughs
expected
Bio-material
Ti or Ti6Al4V substrates
Limited biocompatibility 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
Bio-coatings
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
6Project Presentation
State-of-the-Art
ProblemsHow is this tackled in MEDDELCOAT
Expected breakthroughs
Biofilm inhibi-
tion
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
Ortho-peadic
&dental
Implants
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
Multifunctional bioresorbable coating with biofilm inhibition
Prolonged implant life time (> 25 %),
reduced need for revision surgery,reduced infection
rate
Problem statement & expected breakthroughs
7Project Presentation
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
8Project Presentation
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.
O2The 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-coating-bone interface in such a way to realise optimal implant fixation in combination with osteointegration and biofilm inhibiting functionality.
9Project Presentation
Scientific & technological objectives
No Description
O6Microstructural 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
O8Modelling 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.
10Project Presentation
Scientific & technological objectives
No Description
O11The 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.
O14In 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
11Project Presentation
MEDDELCOAT consortium
LEMI
12Project Presentation
Project structure & partner co-operation
Substrates & powders
Coating and sintering technology
Characterisation and evaluation
Modelling
Bacteria-material interaction
Biocompatibility testing
Dissemination and exploitation (all partners)
LIMA, Helipro, KUL
Alhenia, AMES, KUL-MTM, UoB, IJS
IMMG, KUL-MTM, UoB, IJS
LIMA, HUT, KUL-MTM, UoB
KUL-REGA, OctoPlus
LEMI, Helipro, IJS, KUL-MTM Coa
tin
g d
esig
n &
En
gin
eeri
ng
(al
l par
tner
s)
Tra
inin
g ac
tivi
ties
(al
l par
tner
s)
Selection of implants (LIMA, Helipro)
Substrates & powders (WP1)
Coating and sintering technology (WP2)
Characterisation and evaluation (WP2)
Modelling and finite element analysis (WP2)
Bacteria-material interaction (WP3)
Biocompatibility testing (WP4)
Upscaling feasibility (WP5) all partners
LIMA, HeliPro, AALTO KUL-MTM, ALHENIA, UoB
ALHENIA, AMES, KUL-MTM, UoB, IJS
IMMG, KUL-MTM, UoB, IJS
LIMA, AALTO,KUL-MTM, UoB
KUL-REGA, HEMOTEQ
LEMI, HeliPro, IJS, KUL-MTM
Coa
tin
g d
esig
n &
En
gin
eeri
ng
(WP
2) a
ll p
artn
ers
Tra
inin
g ac
tivi
ties
(W
P7)
all
par
tner
s
Selection of implants (WP1) (LIMA, Heli Pro)
RT
D-a
ctiv
itie
s (
WP
1-W
P5)
all
Inn
ovat
ion
-rel
ated
acti
viti
es (
WP
6) a
ll
Dem
onst
rati
on
acti
viti
es (
WP
8) a
ll
13Project Presentation
Project work plan overview
Task 2.2: Coatings for implant fixation
Task 2.3: Bioresorbable and bioactive coatings
Task 2.4: Thermal treatments
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
Tas
k 2.
1: C
oati
ng e
ngin
eeri
ng &
des
ign
WP 2: Coating of implants
WP 3: Bacteria-coating interaction
WP 4: Biocompatibility and activity testing
Task 3.1: Bacteria-coating interaction investigation
Task 3.2: Selection and incorporation of biofilm inhibitors
Task 3.3: Evaluation of biofilm inhibiting coatings
Task 4.1: Cell culture of powders and coated implants
Task 4.2: Bioactivity and resorbability testing of coatings
Task 4.3: In-vivo testing of bone bonding
WP 1: Substrates & bioactive powders
Task 1.1: Selection & supply of substrates and implants
Task 1.2: Selection & supply of bioactive powders
WP 5: Upscaling feasibilityWP 6: Innovation related activitiesWP 7: Demonstration activities
WP 8: Training activitiesWP 9: Project management
14Project Presentation
Project milestones
No Month Description
M0 0 Signed Consortium Agreement (All Partners)
M1 18Supply of state-of-the-art dental and shoulder implants and hip stems and acetabular cups (HeliPro, LIMA)
M2 12Development and supply of a range of bioactive powders (Alhenia, KUL-MTM, UoB)
M3 6Initial composition definition of the graded Ti metal/bioactive material coating (All Partners)
M4 6State-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 18Supply of the first multi-functional (fixation + bioactive) substrate-coating combination (KUL-MTM, IJS, UoB, Alhenia)
M6 24Supply of the first generation of multi-functional (fixation + bioactive) substrate-coating combination for each processing route (KUL-MTM, IJS, UoB, Alhenia)
M7 24Microstructural characterisation of the vacuum plasma sprayed state-of-the-art coatings and the first advanced multi-functional substrate-coating systems (IJS, KUL-MTM, UoB).
15Project Presentation
Project milestones
No Month Description
M8 30Nanoscale microstructural characterisation of the vacuum plasma sprayed state-of-the-art coatings and the first generation of advanced multi-functional substrate-coating systems (IJS).
M9 24Mechanical characterisation of the first generations of advanced multi-functional substrate-coating systems (IMMG).
M10 18Micromechanical and finite element model for the evaluation of the thermal residual stresses and thermal treatments of the envisaged substrate/coating systems. (AALTO)
M11 24Assessment 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 24Knowledge 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 18Evaluation of cytotoxicity testing of bioactive starting powders and substrates (LEMI)
16Project Presentation
Project milestones
No Month Description
M16 30 Evaluation of cytotoxicity testing of the new coating-substrate systems (LEMI)
M17 36Biocompatibility evaluation of the abrasion wear debris generated in the pin-on-flat tests (LEMI)
M18 24In 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 36Evaluation of bioactivity testing of the substrate/coating systems (LEMI, KUL-MTM)
M20 45Evaluation of bone bonding of the multifunctional substrate/coating systems (Heli- Pro, IJS, KUL-MTM)
M21 45Feasibility study for a continuous microwave heating system for the coating of implants with different geometries (AMES)
M22 42Feasibility 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 36Selection of the multifunctional substrate/coating systems for in vivo bone bonding testing (all Partners).
17Project Presentation
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.
18Project Presentation
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 knowledge-based economy (“Lisbon” objective), sustainable development (“Göteborg” objective), and serves the needs of a traditional SME-intensive 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 knowledge-based society (4 of the 7 research priorities for Europe) and especially enhances the participation of SMEs in ERA.
19Project Presentation
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.
20Project Presentation
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.
21Project Presentation
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.
22Project Presentation
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)
23Project Presentation
Contact
• For further information– Visit: www.meddelcoat.eu
– Project coordinator:
Prof. Dr. ir. Jef VleugelsKatholieke Universiteit Leuven
Departement of Metallurgy and Materials Engineering (MTM)Kasteelpark Arenberg 44, B-3001 Heverlee (Belgium)
phone: +32-16-321244, fax: +32-16-321992E-mail: [email protected]
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