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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - BOOST (Biomimetic trick to re-balance Osteblast-Osteoclast loop in osteoporoSis treatment: a Topological and materials driven approach)

Teaser

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...

Summary

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 aims to fill this gap. The research aims to combine the chemistry, structure and topography of biomaterials with biochemical cues, in order to deliver a smart scaffold targeted to treat OP fractures and to understand in vitro the interaction (coupling) between bone depositing cells (osteoblasts) and bone resorpting cells (osteoclasts).
BOOST will address a full characterisation of human bone tissues in order to reproduce as much as possible the bone features through an ad hoc bioprinter able to combine extrusion and ink-jet printing with a very high resolution. Bioactive materials able to release ions with a therapeutic effect will be used to 3D print, smart, bone-like scaffolds that will be validated in vitro by means of co-culture of osteoblasts and osteoclasts.

Work performed

Bone biopsies have been obtained and fully characterised by means of micro-CT, nanoindentations, compressive tests, X-Ray diffration, Raman confocal spectroscopy and hystological analisys in order to collect a complete set of information to design and prototype new, smart bone scaffolds. Biomimetic materials have been prepared developing strontium containing mesoporous glasses (MBGs) with different size and shape, hydroxylapatite (HA) microspheres and nano-rods and solutions of type I collagen with different concentrations. A protocol for co-cultures of osteoblasts and osteoclasts have been designed and will be used 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. 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. Ink-ket of growth factors on the biomaterial surface has been tested and new approaches for encapsulating the growth factors are under development.

Final results

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 aims to deliver a smart scaffold able 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 will establish 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. BOOST is expected to open a 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. The focus will be on the not yet fully exploited potential of materials science in the biomedical field proving the need for cutting-edge materials –based research able to beneficially change our life quality in a 10-year-time frame.

Website & more info

More info: http://www.ercprojectboost.eu/.