Final Report Summary - MEDDELCOAT (Multifunctional bioresorbable biocompatible coatings with biofilm inhibition and optimal implant fixation)
The MEDDELCOAT project, driven by seven dedicated complementary hi-tech Small and medium-sized enterprises (SMEs), aimed at the development of the next generations of multifunctional bioactive biocompatible coatings with biofilm inhibition and optimal implant fixation that should eliminate the currently experienced need for implant revisions due to implant loosening and infections. In a combinatorial approach, new processing technologies was developed and evaluated for surface structuring of the implant for fixation by osteointegration, the application of a biocompatible and bioactive top coating and the incorporation of a biofilm inhibiting functionality into the coating.
The envisaged radical innovations and major breakthroughs to achieve this goal were:
- 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 the anti-infective substance into the coating.
The Science and technology (S&T) objectives originally set to be realised are summarised in the table below:
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-coating-bone interface in such a way to realise optimal implant fixation in combination with osteointegration and biofilm inhibiting functionality.
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.
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 of 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.
The envisaged radical innovations and major breakthroughs to achieve this goal were:
- 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 the anti-infective substance into the coating.
The Science and technology (S&T) objectives originally set to be realised are summarised in the table below:
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-coating-bone interface in such a way to realise optimal implant fixation in combination with osteointegration and biofilm inhibiting functionality.
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.
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 of 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.