Periodic Reporting for period 3 - GIOTTO (Active aGeIng and Osteoporosis: The next challenge for smarT nanobiOmaterials and 3D technologies)
Periodo di rendicontazione: 2022-01-01 al 2023-08-31
When we think of bone, we should remember that its architecture is not fixed, but it is the result of a dynamic balance between bone resorption and deposition. This process takes place through a perfectly orchestrated coupling of two types of cells: osteoblasts (Ob), responsible for bone deposition and osteoclasts (Oc), responsible for bone resorption. When there is an uncoupling in the cooperative action of these two cell types, bone becomes more porous (osteoporosis means literally porous bone) and there is an increased fracture risk. Osteoporosis (OP) is a worldwide disease, defined in 2001 as “a skeletal disorder characterised by compromised bone strength predisposing a person to an increased risk of fracture” by the National Institutes of Health. Till the beginning of the new millennium this epidemic, progressive disease has been under diagnosed and underestimated until a call for action was launched in 2001 by the International Osteoporosis Foundation (IOF) to be active on policy issues focused on preventing and managing this bone-fragility disease. Nowadays, in the EU, one of us experiences an osteoporotic fracture every 30 seconds and with the current demographic shift the incidence is expected to double in few decades. OP has been for long time identified as a women-only disease and still is by the lay public, but recent data shows that it affects 1 out of 2-3 women and 1 out of 5 men above fifty years, and that the prognosis for men is often significantly worse. Approximatively 22 million women and 5.5 million men aged between 50-84 years are estimated to be affected by OP in the EU . Fighting OP and developing ad hoc medical devices and approaches to treat osteoporotic fractures and to support bone regeneration in a diseased environment are strategic goals of the next decade and should become a worldwide priority for governments.
The main objective of the GIOTTO project is to face this osseous, degenerative pathology through a dedicated, precise and personalised approach.
OP can lead to different types of fractures located in dissimilar body parts and thus the main project objective have targeted the development of three different medical devices designed to treat specific osteoporotic fractures through a synergistic convergence of smart nanomaterials, 3D fabrication technologies and targeted cell activation. The overall objective of GIOTTO is then to implement solutions and tools to enhance active ageing thereby mitigating the economic burden to health systems and bringing within grasp benefits for the elderly.
The main objective of the GIOTTO project is to face this osseous, degenerative pathology through a dedicated, precise and personalised approach.
OP can lead to different types of fractures located in dissimilar body parts and thus the main project objective have targeted the development of three different medical devices designed to treat specific osteoporotic fractures through a synergistic convergence of smart nanomaterials, 3D fabrication technologies and targeted cell activation. The overall objective of GIOTTO is then to implement solutions and tools to enhance active ageing thereby mitigating the economic burden to health systems and bringing within grasp benefits for the elderly.
In the first reporting period the clinical specification and the design of the three devices have been implemented.
In particular:
* Device 1 was defined as a graded 3D scaffold that will act as a bio-stimulatory augment to existing periprosthetic femur plates.
For device 1, the consortium developed and evaluated a series of polymeric resorbable blends to be filament extruded together with the bioactive inorganic phases.
* Device 2 will be a resorbable fibrous composite to treat confined pelvic fractures.
For device 2 the consortium focused on electrospinning type I collagen solutions (from different sources) using different solvents and adding different concentration of the developed inorganic phases.
* Device 3 will be a resorbable, radiopaque, injectable bone cement to treat vertebral compression fractures.
For device 3 the consortium worked on the development of a radiopaque phase to be added to a resorbable and injectable ceramic paste based on calcium sulphate.
For all the three devices, different strategies have been planned and developed in order to vehicle an active molecule able to inhibit osteoclast resorption (ICOS-Fc) so that the complete device would stimulate osteoblast activity while inhibiting osteoclast one.
In parallel, the consortium worked on the production of small and homogenous superparamagnetic iron oxide nanoparticles functionalised wit RGD peptides to trigger cell mechanotransduction upon remote activation by an external magnetic field.
The work performed in the second reporting period led to the following results:
Device 1, Device 2 and Device 3 development and characterisation have been successfully completed and in vivo test on the best performing prototypes are currently on going.
ICOS-Fc has been incorporated into the three different devices using ad hoc strategies and maintained its activity after both incorporation and sterilisation process.
TRL5 routes for the materials and device manufacturing have been in part implemented to TRL5 but the work will continue in the next reporting period.
The work performed in the third reporting period completed the development of the three devices at TRL5 and their validation using in vivo pre-clinical models.
Key exploitable results were identified and the path towards their exploitation discussed and agreed.
In addition to the three KERs related to the devices other exploitable results were identified by the industrial consortium partners reaching an overall number of 10 for which the lead partners, the steps required for the actual exploitation and the related timing were defined.
Dissemination and communication activities were continuously promoted leading to the publication of 26 open access publication and the production of 3 videos.
In particular:
* Device 1 was defined as a graded 3D scaffold that will act as a bio-stimulatory augment to existing periprosthetic femur plates.
For device 1, the consortium developed and evaluated a series of polymeric resorbable blends to be filament extruded together with the bioactive inorganic phases.
* Device 2 will be a resorbable fibrous composite to treat confined pelvic fractures.
For device 2 the consortium focused on electrospinning type I collagen solutions (from different sources) using different solvents and adding different concentration of the developed inorganic phases.
* Device 3 will be a resorbable, radiopaque, injectable bone cement to treat vertebral compression fractures.
For device 3 the consortium worked on the development of a radiopaque phase to be added to a resorbable and injectable ceramic paste based on calcium sulphate.
For all the three devices, different strategies have been planned and developed in order to vehicle an active molecule able to inhibit osteoclast resorption (ICOS-Fc) so that the complete device would stimulate osteoblast activity while inhibiting osteoclast one.
In parallel, the consortium worked on the production of small and homogenous superparamagnetic iron oxide nanoparticles functionalised wit RGD peptides to trigger cell mechanotransduction upon remote activation by an external magnetic field.
The work performed in the second reporting period led to the following results:
Device 1, Device 2 and Device 3 development and characterisation have been successfully completed and in vivo test on the best performing prototypes are currently on going.
ICOS-Fc has been incorporated into the three different devices using ad hoc strategies and maintained its activity after both incorporation and sterilisation process.
TRL5 routes for the materials and device manufacturing have been in part implemented to TRL5 but the work will continue in the next reporting period.
The work performed in the third reporting period completed the development of the three devices at TRL5 and their validation using in vivo pre-clinical models.
Key exploitable results were identified and the path towards their exploitation discussed and agreed.
In addition to the three KERs related to the devices other exploitable results were identified by the industrial consortium partners reaching an overall number of 10 for which the lead partners, the steps required for the actual exploitation and the related timing were defined.
Dissemination and communication activities were continuously promoted leading to the publication of 26 open access publication and the production of 3 videos.
Chronic diseases such as osteoporosis represent a heavy burden to aging societies and maintenance of health with aging is an important societal challenge, now and in the years to come.
In developed countries, the lifetime risk for osteoporotic fractures at the wrist, hip or spine is currently 30% to 40%, very close to that for coronary heart disease. More than 1.5 million hip fractures occur each year across the world, and this number is estimated to increase up to 4.5 million by 2050 . Therefore, the innovative solutions proposed by GIOTTO are expected to have substantial impacts from the social, personal-health and active-ageing perspectives. GIOTTO combined a recombinant molecule (ICOS-Fc) with the 3 devices targeted to treat and heal osteoporotic fractures, able to support bone regeneration through 3D architecture and chemical cues, to stabilise the fracture due to its engineered structure and to stimulate bone healing through the release of osteoproductive agents, going well beyond the State-of-the Art. GIOTTO devices will be biologically active through the action of ICOS-Fc and will incorporate inorganic phases well-known for their ability to stimulate bone regeneration (nano-hydroxyapatite and mesoporous bioactive glass incorporating ions able to elicit a specific biological function). The overall approach has been integrated with a specific design of the device architecture achieved leveraging on key biofabrication techniques of extrusione printing and direct writing electrospinning.
Project partners worked in close contact with clinicians aiming at providing a detailed, shared and realistic description of all features of the devices under development (user needs). From the indications provided by clinicians, we continuously worked on defining the device specifications (design inputs) and on providing evidence that devices produced according to such specifications meet all defined acceptance criteria. This information flowed in the Technical Design Dossier structure providing the basis for the exploitation of the KERs as defined in the Exploitation Plan.
In developed countries, the lifetime risk for osteoporotic fractures at the wrist, hip or spine is currently 30% to 40%, very close to that for coronary heart disease. More than 1.5 million hip fractures occur each year across the world, and this number is estimated to increase up to 4.5 million by 2050 . Therefore, the innovative solutions proposed by GIOTTO are expected to have substantial impacts from the social, personal-health and active-ageing perspectives. GIOTTO combined a recombinant molecule (ICOS-Fc) with the 3 devices targeted to treat and heal osteoporotic fractures, able to support bone regeneration through 3D architecture and chemical cues, to stabilise the fracture due to its engineered structure and to stimulate bone healing through the release of osteoproductive agents, going well beyond the State-of-the Art. GIOTTO devices will be biologically active through the action of ICOS-Fc and will incorporate inorganic phases well-known for their ability to stimulate bone regeneration (nano-hydroxyapatite and mesoporous bioactive glass incorporating ions able to elicit a specific biological function). The overall approach has been integrated with a specific design of the device architecture achieved leveraging on key biofabrication techniques of extrusione printing and direct writing electrospinning.
Project partners worked in close contact with clinicians aiming at providing a detailed, shared and realistic description of all features of the devices under development (user needs). From the indications provided by clinicians, we continuously worked on defining the device specifications (design inputs) and on providing evidence that devices produced according to such specifications meet all defined acceptance criteria. This information flowed in the Technical Design Dossier structure providing the basis for the exploitation of the KERs as defined in the Exploitation Plan.