Periodic Reporting for period 1 - INKplant (INK-BASED HYBRID MULTI-MATERIAL FABRICATION OF NEXT GENERATION IMPLANTS)
Reporting period: 2021-01-01 to 2022-06-30
The vision of INKplant is to combine different new biomaterials, high resolution 3D-printing technologies (bi-material lithography-based ceramic manufacturing - LCM, multi-material inkjet printing) with new simulation & modelling and biological evaluation methods. This allows the design and fabrication of multi-material biomimetic scaffolds with appropriate composition and microstructure that induce tissue-specific regeneration, addressing the complexity of different tissues in the human body and consideration of the individual variations to patient´s requirements.
INKplant Use Cases (UC) will provide solutions to patients suffering from chronic defects of joints (UC 1) or dental tissues (UC 2) who have severely decreased life quality and depend continuously on health care. As 22% of the European population will be aged over 65 by the year 2025, rising to almost 30% by 2050, regenerative approaches become more important to sustainably heal and avoid further treatments.
INKplant aims at the future incorporation of 3D-printed scaffolds into the daily routine of medical practice to foster personalized regenerative therapies for the whole society (concept shown in Figure1).
These overall objectives are set:
To develop innovative manufacturing technologies for affordable patient-specific scaffolds;
To create a workflow for the design optimization of 3D printed scaffolds,
To demonstrate the INKplant approach in two different Use Cases (UC),
To assure the future translation of the technology to clinical application, via European regulatory approval and commercialization.
INKplant Use Cases (UC) will provide solutions to patients suffering from chronic defects of joints (UC 1) or dental tissues (UC 2) who have severely decreased life quality and depend continuously on health care. As 22% of the European population will be aged over 65 by the year 2025, rising to almost 30% by 2050, regenerative approaches become more important to sustainably heal and avoid further treatments.
INKplant aims at the future incorporation of 3D-printed scaffolds into the daily routine of medical practice to foster personalized regenerative therapies for the whole society (concept shown in Figure1).
These overall objectives are set:
To develop innovative manufacturing technologies for affordable patient-specific scaffolds;
To create a workflow for the design optimization of 3D printed scaffolds,
To demonstrate the INKplant approach in two different Use Cases (UC),
To assure the future translation of the technology to clinical application, via European regulatory approval and commercialization.
WP1 All meetings performed, Sample ID database was prepared.
WP2 Definition of concepts, requirements and specifications for: materials & fabrication processes, test structures & cell studies, modelling & design, use cases and for future clinical applications was completed
WP3
Update of LCM multi-material printer regarding software (SW) & hardware (HW) was completed
Qualification strategy established (Quality & boundary parameter assessment started by mono-material printing)
New zirconia ink was printed, debinded, sintered and characterized
New HA ink fully developed, curing tested regarding co-sintering with zirconia ink
WP4
Inkjet printability of 2 nano-hydroxyapatite (nHAp) based ink formulations proved with industrial printheads, long-term stability proved
Ink hydrogel found to be suitable only for dispensing
Biodegradable polymer ink (Ink-BDP) (non biodegradable polymer) and Ink-BDP-PPZ (biodegradable) formulations were used for fabrication of 3D inkjet printed samples
Polydimethylsiloxane based ink (Ink-PDMS) UV-curable formulation was inkjet 3D printed with a PolyJet but required material properties of cured PDMS could not be obtained
3D multi-material inkjet printing module was upgraded (HW & SW)
WP5
5-Axis multi-material 3D inkjet printing system developed, including first SW control strategy for printing 3D parts on curved surfaces
Biomimetic tests structures TS were developed, fabricated by 3DP-casting methods and fused deposition modeling (FDM) printing for composite UC1.1 and UC1.2 models
WP6
Open source collection of scaffold designs, for different mono- and multi-material additive manufacturing (AM) methods and a library of micro-textured surfaces
Design strategy for personalized scaffolds mimicking biomechanics of healthy tissues developed and prototypes for different UC fabricated.
Study on biomechanics of all UC was completed
Modeling of AM processes was improved for multi-material ceramic parts.
Ethical, legal and social aspects mapped along the lifecycle of tissue engineering (TE) scaffolds, including results of study & specification of quality requirements from medical images to printing process for personalized scaffolds.
WP7
Criteria for in-vitro biocompatibility testing were specified
Cytotoxicity tests of new inks done
Biodegradability of BDP inks was confirmed.
Mechanical characteristics of ceramic materials were determined, for PDMS reference materials were used.
Implant design for in-vivo tests was specified.
WP8
MRI scans database identified
3D model of UC2.1 Palatal defect, was designed and fabricated
Network connections to experts regarding quality assurance and regulation compliance established
WP9
Text data mining of web-forums completed
Open Call for UC launched, a technological portfolio was provided
Analysis on ethical and societal challenges completed and a review submitted
First user acceptance study (focus group) with patients conducted
Gender dimensions were identified
Planning for first stakeholder and lead user workshops done.
WP10
Press release, website, branding, etc
External Advisory Board and EU-H2020 projects meetings
Open-science i-INKplant platform
Updates of exploitation and sustainability & international impact plans
WP2 Definition of concepts, requirements and specifications for: materials & fabrication processes, test structures & cell studies, modelling & design, use cases and for future clinical applications was completed
WP3
Update of LCM multi-material printer regarding software (SW) & hardware (HW) was completed
Qualification strategy established (Quality & boundary parameter assessment started by mono-material printing)
New zirconia ink was printed, debinded, sintered and characterized
New HA ink fully developed, curing tested regarding co-sintering with zirconia ink
WP4
Inkjet printability of 2 nano-hydroxyapatite (nHAp) based ink formulations proved with industrial printheads, long-term stability proved
Ink hydrogel found to be suitable only for dispensing
Biodegradable polymer ink (Ink-BDP) (non biodegradable polymer) and Ink-BDP-PPZ (biodegradable) formulations were used for fabrication of 3D inkjet printed samples
Polydimethylsiloxane based ink (Ink-PDMS) UV-curable formulation was inkjet 3D printed with a PolyJet but required material properties of cured PDMS could not be obtained
3D multi-material inkjet printing module was upgraded (HW & SW)
WP5
5-Axis multi-material 3D inkjet printing system developed, including first SW control strategy for printing 3D parts on curved surfaces
Biomimetic tests structures TS were developed, fabricated by 3DP-casting methods and fused deposition modeling (FDM) printing for composite UC1.1 and UC1.2 models
WP6
Open source collection of scaffold designs, for different mono- and multi-material additive manufacturing (AM) methods and a library of micro-textured surfaces
Design strategy for personalized scaffolds mimicking biomechanics of healthy tissues developed and prototypes for different UC fabricated.
Study on biomechanics of all UC was completed
Modeling of AM processes was improved for multi-material ceramic parts.
Ethical, legal and social aspects mapped along the lifecycle of tissue engineering (TE) scaffolds, including results of study & specification of quality requirements from medical images to printing process for personalized scaffolds.
WP7
Criteria for in-vitro biocompatibility testing were specified
Cytotoxicity tests of new inks done
Biodegradability of BDP inks was confirmed.
Mechanical characteristics of ceramic materials were determined, for PDMS reference materials were used.
Implant design for in-vivo tests was specified.
WP8
MRI scans database identified
3D model of UC2.1 Palatal defect, was designed and fabricated
Network connections to experts regarding quality assurance and regulation compliance established
WP9
Text data mining of web-forums completed
Open Call for UC launched, a technological portfolio was provided
Analysis on ethical and societal challenges completed and a review submitted
First user acceptance study (focus group) with patients conducted
Gender dimensions were identified
Planning for first stakeholder and lead user workshops done.
WP10
Press release, website, branding, etc
External Advisory Board and EU-H2020 projects meetings
Open-science i-INKplant platform
Updates of exploitation and sustainability & international impact plans
Obj1:
M18: Bi-material ceramic printing process developed.
M36: Ceramic ink formulations adapted for co-firing process for bi-material part fabrication.
Obj2:
M18: Inkjet printing of 3 nHAp and 3 BDP formulations & subsequent curing, 3D inkjet printing of BDP and 2D inkjet with nHAp achieved, Ink-nHAp used with industrial print head
M36: 3D multi-material inkjet printing with 2 BDP formulations and PDMS formulations. All bio-inks to be used with industrial printheads
Obj3:
M18: 5-Axis multi-material 3D inkjet printing system developed with a first SW control used for printing 3D structures on curved surfaces.
M36: Optimized SW and workflow for fabrication of hybrid INKplant implants
Obj 4,5,6:
M18: Simulations of deformations of constructs for LCM parts. Model considering volumetric contraction between materials for multi-material sintering done, study on actual evolution of mechanical properties and stresses developed.
For the combined design approach, topology and topography optimization routs were conceived, biomechanical simulations were done and modelling of fabrication processes
Standardized computational design workflow was proposed and optimized for improved repeatability and usability
M36: Combined design approach including all aspects of Obj 4 &5 will be achieved
Integrated workflow from image data to printable files will be achieved.
Potential impact of the project results so far are related to enhanced competitiveness of biomaterials and biomedical industry in the EU through interdisciplinary technology transfer. Examples of Activities therefore are:
Partners shared expertise on certification of biomaterials.
A H2020 projects session at the M3d+it 2021, workshops at the TERMIS EU 2022 organized, participation in the workshop on regulatory aspects of AM medical devices, among H2020 projects where info on requirements for certification of final INKplants was obtained.
Interactions with standardization committees (ISO/TC 150 of JWG1), partners participate and contribute to the development of a new standard based on ISO 14630.
Launch of i-INKplant platform to openly share the collection of scaffold designs with design maps for mono- and multi-material printing, considering printing processes, and a collection of surface topographies.
Those have a potential wider socio-economic impact on fostering OI in TE solutions and AM technologies advancements, leading to a better performance of custom made biomaterials and scaffolds for tissue repair, which in future will lead to reduction of health care costs by faster rehabilitation and reduced medical device associated infections.
M18: Bi-material ceramic printing process developed.
M36: Ceramic ink formulations adapted for co-firing process for bi-material part fabrication.
Obj2:
M18: Inkjet printing of 3 nHAp and 3 BDP formulations & subsequent curing, 3D inkjet printing of BDP and 2D inkjet with nHAp achieved, Ink-nHAp used with industrial print head
M36: 3D multi-material inkjet printing with 2 BDP formulations and PDMS formulations. All bio-inks to be used with industrial printheads
Obj3:
M18: 5-Axis multi-material 3D inkjet printing system developed with a first SW control used for printing 3D structures on curved surfaces.
M36: Optimized SW and workflow for fabrication of hybrid INKplant implants
Obj 4,5,6:
M18: Simulations of deformations of constructs for LCM parts. Model considering volumetric contraction between materials for multi-material sintering done, study on actual evolution of mechanical properties and stresses developed.
For the combined design approach, topology and topography optimization routs were conceived, biomechanical simulations were done and modelling of fabrication processes
Standardized computational design workflow was proposed and optimized for improved repeatability and usability
M36: Combined design approach including all aspects of Obj 4 &5 will be achieved
Integrated workflow from image data to printable files will be achieved.
Potential impact of the project results so far are related to enhanced competitiveness of biomaterials and biomedical industry in the EU through interdisciplinary technology transfer. Examples of Activities therefore are:
Partners shared expertise on certification of biomaterials.
A H2020 projects session at the M3d+it 2021, workshops at the TERMIS EU 2022 organized, participation in the workshop on regulatory aspects of AM medical devices, among H2020 projects where info on requirements for certification of final INKplants was obtained.
Interactions with standardization committees (ISO/TC 150 of JWG1), partners participate and contribute to the development of a new standard based on ISO 14630.
Launch of i-INKplant platform to openly share the collection of scaffold designs with design maps for mono- and multi-material printing, considering printing processes, and a collection of surface topographies.
Those have a potential wider socio-economic impact on fostering OI in TE solutions and AM technologies advancements, leading to a better performance of custom made biomaterials and scaffolds for tissue repair, which in future will lead to reduction of health care costs by faster rehabilitation and reduced medical device associated infections.