Periodic Reporting for period 3 - FAST (Functionally graded Additive Manufacturing scaffolds by hybrid manufacturing)
Période du rapport: 2018-06-01 au 2019-11-30
People have always had to face the need of repairing parts of the body, mainly limbs and teeth, in the aftermath of ageing, injuries or diseases. For centuries prostheses have been the solution. New materials such as polymers, composites, and electronics have allowed a strong improvement in the performances of these devices, from hearing aids to the carbon fibre foot for runners. Such developments are improving the daily life of many people allowing a better lifestyle.
However, the development of materials has allowed an even deeper advance for human health: the possibility of implanting parts of the body spanning from bones such as femur, up to cardiac valves or stents. “Biocompatibility” has been the master rule for the development of implantable materials and devices for decades. The results of these researches are now common tools for healthcare, such as dental implants.
From the late ‘90ies, biological research advances on one side and material developments on the other side have allowed to think even further. The goal of the developments shifted from tissue replacement to tissue regeneration. In the future, we will not have an implanted metallic ankle, but a new regrown bone.
Our body has an innate capacity to regenerate itself. However, when critical size defects are presented (e.g. typically in the range of at least one cubic centimetre), tissue regeneration strategies are needed. Tissue regeneration is a complex topic that requires a multidisciplinary approach, from (stem) cell biology and cell growth to the interface interactions between materials and cells. From a technological point of view, “scaffolds”, i.e. temporary porous structures housing cells, and “bio-degradable” materials are the new master rules for the development of tissue regeneration constructs. The challenge to address when fabricating scaffolds lies in the fact that the organization of tissues and organs in the human body is difficult to replicate. Scaffolds need open and completely interconnected pores with dimensions typical in the order of hundreds of microns but also nano-scale morphology, surface chemistry but also mechanical properties to guide the desired cell activity and tissue formation.
The FAST project aims to offer a novel production device able to obtain in a single production process all these requirements, hybridising the Additive Manufacturing (AM) technology with melt compounding and atmospheric plasma.
To AM flexibility, melt compounding adds the possibility to deposit not only polymers, but also polymer nano-composites with high content of nanofillers improving mechanical properties, allowing smart functionalities (antibiotic release, …) or guiding stem cell differentiation to obtain the desired tissue growth.
Atmospheric plasma treatment or deposition during AM allows surface chemical functionalization, further controlling cell adhesion and proliferation.
These technological advances allow a cost reduction, the possibility to make scaffolds affordably available and may hold the potential to improve patient lifestyle by reducing the recovery duration.
However, the development of materials has allowed an even deeper advance for human health: the possibility of implanting parts of the body spanning from bones such as femur, up to cardiac valves or stents. “Biocompatibility” has been the master rule for the development of implantable materials and devices for decades. The results of these researches are now common tools for healthcare, such as dental implants.
From the late ‘90ies, biological research advances on one side and material developments on the other side have allowed to think even further. The goal of the developments shifted from tissue replacement to tissue regeneration. In the future, we will not have an implanted metallic ankle, but a new regrown bone.
Our body has an innate capacity to regenerate itself. However, when critical size defects are presented (e.g. typically in the range of at least one cubic centimetre), tissue regeneration strategies are needed. Tissue regeneration is a complex topic that requires a multidisciplinary approach, from (stem) cell biology and cell growth to the interface interactions between materials and cells. From a technological point of view, “scaffolds”, i.e. temporary porous structures housing cells, and “bio-degradable” materials are the new master rules for the development of tissue regeneration constructs. The challenge to address when fabricating scaffolds lies in the fact that the organization of tissues and organs in the human body is difficult to replicate. Scaffolds need open and completely interconnected pores with dimensions typical in the order of hundreds of microns but also nano-scale morphology, surface chemistry but also mechanical properties to guide the desired cell activity and tissue formation.
The FAST project aims to offer a novel production device able to obtain in a single production process all these requirements, hybridising the Additive Manufacturing (AM) technology with melt compounding and atmospheric plasma.
To AM flexibility, melt compounding adds the possibility to deposit not only polymers, but also polymer nano-composites with high content of nanofillers improving mechanical properties, allowing smart functionalities (antibiotic release, …) or guiding stem cell differentiation to obtain the desired tissue growth.
Atmospheric plasma treatment or deposition during AM allows surface chemical functionalization, further controlling cell adhesion and proliferation.
These technological advances allow a cost reduction, the possibility to make scaffolds affordably available and may hold the potential to improve patient lifestyle by reducing the recovery duration.
In standard additive manufacturing (AM) platforms for scaffolds fabrication, only one fabrication technology is available, such as 3D printing, fused deposition modelling (FDM), or selective laser sintering (SLS). Only one material per time can be used leading to discrete compositional changes. From a chemical or morphological point of view, surface treatments are usually performed after scaffold fabrication, thus resulting in more laborious procedures.
The FAST project aims to integrate different technologies in a single hybrid AM platform (HAM) to improve flexibility in scaffolds’ design and production. The novel platform allows to make compositional gradients and surface functionalisation in the same scaffold production process in a continuous production flow manner.
All the technological developments started simultaneously, the new composite materials optimized for bone regeneration, the novel atmospheric plasma jet and the printing heads. The developed devices have been successfully integrated in two prototypes. Then, a pilot production of scaffolds with different geometries and gradients have been performed and tested up to a preclinical animal model.
What does the HAM allows to fabricate and gradually control?
• Deposit polymer with melting index up to 250°C, such as PEOT/PBT (scaled up to GMP grade);
• Add a controlled release of intercalated antibiotics, offering a targeted and localised protection against infections, by use of lamellar fillers based on hydrotalcites loaded with antibiotics;
• Add smart fillers to offer protection against infections and support cell growth and differentiation, such as reduced-GO (r-GO);
• Add nano-hydroxyapatite filler up to 60 w%;
• Add surface functionalisation locally, for example amine and epoxy groups, while printing by atmospheric plasma jet (APPJ)
• Predict the mechanical properties as a function of geometry and composition
• Design-by-function 3D scaffolds displaying physicochemical gradients for bone regeneration
The possibility to created gradient designs in the in vivo experiments has shown interesting results in guiding cells growth, and therefore in speeding up bone reconstruction.
All these developments are carried on keeping in mind ethics and safety rules not only for the research and development itself, but also for the future manufacturing and exploitation on larger scale. In order to help the observance of the nanosafety requirements, the project became part of the “Industrial Innovation Liaison (i2L)”, which is part of the NanoSafety Cluster as well as in the European Pilot Production Network as a cross-linking working group.
The scientific results have been presented in several conferences and the HAM devices and novel materials are entering in the market.
The FAST project aims to integrate different technologies in a single hybrid AM platform (HAM) to improve flexibility in scaffolds’ design and production. The novel platform allows to make compositional gradients and surface functionalisation in the same scaffold production process in a continuous production flow manner.
All the technological developments started simultaneously, the new composite materials optimized for bone regeneration, the novel atmospheric plasma jet and the printing heads. The developed devices have been successfully integrated in two prototypes. Then, a pilot production of scaffolds with different geometries and gradients have been performed and tested up to a preclinical animal model.
What does the HAM allows to fabricate and gradually control?
• Deposit polymer with melting index up to 250°C, such as PEOT/PBT (scaled up to GMP grade);
• Add a controlled release of intercalated antibiotics, offering a targeted and localised protection against infections, by use of lamellar fillers based on hydrotalcites loaded with antibiotics;
• Add smart fillers to offer protection against infections and support cell growth and differentiation, such as reduced-GO (r-GO);
• Add nano-hydroxyapatite filler up to 60 w%;
• Add surface functionalisation locally, for example amine and epoxy groups, while printing by atmospheric plasma jet (APPJ)
• Predict the mechanical properties as a function of geometry and composition
• Design-by-function 3D scaffolds displaying physicochemical gradients for bone regeneration
The possibility to created gradient designs in the in vivo experiments has shown interesting results in guiding cells growth, and therefore in speeding up bone reconstruction.
All these developments are carried on keeping in mind ethics and safety rules not only for the research and development itself, but also for the future manufacturing and exploitation on larger scale. In order to help the observance of the nanosafety requirements, the project became part of the “Industrial Innovation Liaison (i2L)”, which is part of the NanoSafety Cluster as well as in the European Pilot Production Network as a cross-linking working group.
The scientific results have been presented in several conferences and the HAM devices and novel materials are entering in the market.
The FAST project aims to develop and offer to the market a novel Hybrid Additive Manufacturing (HAM) device for producing scaffolds for tissue regeneration. The HAM device and materials developed in the project are focused on bone regeneration applications.
The implementation of HAM technologies enables the localized production of the scaffolds by synthetic materials making them therefore easily available in the needed quantity also in less technological advanced areas. This feature will have a strong social impact in satisfying the increasing demand of scaffolds. Furthermore, the bio-active features will allow a reduction of the infections due to surgery. Moreover, there will be no more need of donors of cells, since the scaffolds can be combined with patient (stem) cells from the bone marrow directly in the surgical procedure. Therefore, the uptake of the HAM technology holds the potential to lead to a better quality of life for each individual patient, which will make a positive social impact. At the moment, no AM device is present on the market that includes the hybrid features proposed in the FAST project.
The implementation of HAM technologies enables the localized production of the scaffolds by synthetic materials making them therefore easily available in the needed quantity also in less technological advanced areas. This feature will have a strong social impact in satisfying the increasing demand of scaffolds. Furthermore, the bio-active features will allow a reduction of the infections due to surgery. Moreover, there will be no more need of donors of cells, since the scaffolds can be combined with patient (stem) cells from the bone marrow directly in the surgical procedure. Therefore, the uptake of the HAM technology holds the potential to lead to a better quality of life for each individual patient, which will make a positive social impact. At the moment, no AM device is present on the market that includes the hybrid features proposed in the FAST project.