Biomimetic trick to re-balance Osteblast-Osteoclast loop in osteoporoSis treatment: a Topological and materials driven approach

Informations projet

BOOST

N° de convention de subvention: 681798

DOI

10.3030/681798

Projet clôturé

Date de signature de la CE 23 Avril 2016

Date de début 1 Mai 2016

Date de fin 30 Juin 2022

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 977 500,00

Contribution de l’UE

€ 1 977 500,00

Coordonné par

POLITECNICO DI TORINO
Italy

Periodic Reporting for period 4 - BOOST (Biomimetic trick to re-balance Osteblast-Osteoclast loop in osteoporoSis treatment: a Topological and materials driven approach)

Période du rapport: 2020-11-01 au 2022-06-30

Résumé du contexte et des objectifs généraux du projet

Osteoporosis (OP) is a common, worldwide disease with a rapidly growing incidence as the population ages; it results in bone loss and deterioration and in a decreased bone strength, which involve an increase in the risk of fractures.
The main clinical consequences of this condition are bone fractures, which are associated with significant morbidity and mortality. Fragility fractures are linked with substantial pain and suffering, disability and even the death of the affected patients as well as substantial costs for the society. The economic burden of fractures has increased over the last decade and the number of fractures projected for 2025 will reach 3.2 million, with health care costs up to 38.5 billion Euros, due to Europe’s ageing population. This disease has a very high frequency in people over 50 and it has been calculated that 1 in 5 men and 1 in 3 women over 50 will experience an osteoporotic fracture in their lifetime.
At present, a purposely developed scaffold for treating OP fracture does not exist and the BOOST project aimed to fill this gap.
BOOST fully characterised healthy and osteoporotic human bone tissues using several technics and reproduced the observed chemical and biological features as well as the bone architecture with 3D scaffold printed through an ad hoc engineered 3D printing platform allowing for high resolution printing.
Protocols of co-cultures of osteoblasts and osteoclasts have been developed and used to validated the biofabricated scaffolds.
During the project, the protocol of co-culture have been used to understand the interaction (coupling) between bone depositing cells (osteoblasts) and bone resorpting cells (osteoclasts).

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Bone biopsies have been obtained and fully characterised by means of micro-CT, nanoindentations, compressive tests, X-Ray diffraction, Raman confocal spectroscopy and hystological analises in order to collect a complete set of information to design and prototype new, smart bone scaffolds. Data have been shared with the scientific community.
Biomimetic materials have been prepared developing strontium containing mesoporous glasses (MBGs) with different size and shape, physiological like hydroxylapatite (HA) nano-rods and solutions of bovine or rat type I collagen at different concentrations. A protocol for co-cultures of osteoblasts and osteoclasts have been designed and validated to evaluate the developed biomaterials and the extruded 3D scaffolds. To design nanostructured bioactive constructs mimicking the natural bone environment, different hybrid systems based on the combination of type I collagen and micro- or nano-sized particles of strontium-containing mesoporous glass have been optimised and characterized, with a special focus on their printability and biological properties. Two different supporting baths have been optimised and tested in order to allow printing of high-resolution scaffolds with increase printing fidelity and characterised by complex geometries such as those derived from nano-computed tomography of human bone samples. A new 3D bioprinter, which integrates multiple bioprinting technologies and micrometrical resolution in positioning, was designed and prototyped. It includes a print head for bioextruding collagen suspensions with MBG and HA, combined with inkjet cartridges for printing growth factors.
Several cross-linking methods have been explored in order to increase the stability and mechanical properties of the finale 3D constructs and to avoid the premature release of therapeutic ions.
Ink-jet of growth factors on the biomaterial surface has been tested and new approaches for encapsulating the growth factors in order to release them upon acidic pH to simulate their release in the human bone upon osteoclast resorption have been developed.
20 open access papers have been already published and are available to the scientific community and other 3 are currently under drafting.
Extensive conference and event participation have been carried out with about 70 different actions.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The BOOST project aims to codify how biomaterial chemistry and topography at the macro-, micro- and nano-scale influence the multifaceted coupling process of bone resorption and formation, with special emphasis on the cell cross-talk between osteoclasts and osteoblasts. Based on a complete human bone tissue characterisation, the BOOST project delivered a smart scaffold mimicking healthy human bone features in order to trigger a physiological bone remodelling in the unbalanced situations of bone diseases (e.g. osteoporosis).
The research carried out in the frame of the BOOST project established a benchmark for bone engineering to define the key parameters for the ideal 3D bone scaffold: type and amount of therapeutic ions to be released to stimulate bone regeneration, material surface area and particle size, topography and porosity features, amount and type of extracellular matrix derived signals to be encased in the scaffold trabeculae. Release of bone encased growth factors upon osteoclast resorption has been simulated with smart nanobiomaterials able to respond to acidic pH values.
BOOST opened new horizons and approaches for the treatment of bone pathologies, focusing on osteoporosis, a burden that affects tens of millions of people and resulting in a reduction of its socio-economic impact, which exceeds those of migraine, stroke and Parkinson disease.

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