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Active aGeIng and Osteoporosis: The next challenge for smarT nanobiOmaterials and 3D technologies

Periodic Reporting for period 1 - GIOTTO (Active aGeIng and Osteoporosis: The next challenge for smarT nanobiOmaterials and 3D technologies)

Reporting period: 2019-01-01 to 2020-05-31

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 will be targeted through 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 work performed in this first reporting period was targeted to the development of the innovative materials to fabricate the three GIOTTO devices and to the definition of the design input in accordance with the clinicians involved in the Stakeholder Board.
Bioactive inorganic phases containing terapeutic ions have been developed and fully characterised (nano-hydroxyapatites and mesoporous bioactive glasses).
* 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 frctures.
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.
In vitro characterisation of all the produced materials has been performed with promising results.
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 ambition is to combine a recombinant molecule (ICOS-Fc) with a medical device 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 will be integrated with a specific design of the device architecture that will be achieved leveraging on key biofabrication techniques.
Right from project start, project partners worked in close contact with Stakeholder Board 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, project partners 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 continuously flows in the Technical Design Dossier structure providing the basis for the exploitation of the work performed in GIOTTO
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