Multifunctional bioresorbable biocompatible coatings with ...

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


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.


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


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


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


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


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.



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.



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


MEDDELCOAT consortium

LEMI


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, Heli Pro, HUT KUL-MTM, ALHENIA, UoB

ALHENIA, AMES, KUL-MTM, UoB, IJS

IMMG, KUL-MTM, UoB, IJS

LIMA, HUT,KUL-MTM, UoB

KUL-REGA, HEMOTEQ

LEMI, Heli Pro, 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


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


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 (Heli Pro, 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).


Project milestones


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. (TKK)

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)


Project milestones


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).


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.



• 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.



– 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.



• 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.



• 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.


Administrative information

• Project– Type: IP-SME

– Contract no.: NMP3-CT-2006-02651

– www.meddelcoat.eu

• Project duration: 01/10/2006 – 30/9/2010• 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)


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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