GRACE

Growth factor release upon acidic environment in bone resorption.

January 12^th 2018 – January 11^th 2022

Budget: € 158.201,00

Coordinator: Prof. Chiara Vitale-Brovarone

The dynamic process between bone resorption by means of osteoclasts (Oc) and new bone deposition by osteoblasts (Ob) in bone tissue is called bone remodeling and is driven by a precise exchange of biochemical signals between Oc and Ob (coupling). With age, bone resorption can progressively overcome bone deposition, thus leading to a reduction in bone mass and quality and to an overall picture of bone fragility (osteoporosis).

During bone remodeling, the resorption of bone portions by active Oc involves the excretion of enzymes that are able to digest the collagenous fibers and locally alter the pH, thus leading to the dissolution of the mineral phase (hydroxyapatite - HA). When this occurs, the growth factors (GF) stored in the bone matrix are released and they stimulate Ob migration and activity, which lead to new bone deposition in the reabsorbed area.

In the ERC BOOST smart scaffold, a chemical bond between the GF and the scaffold components will be created, but premature GF release is likely to occur due to an insufficient linkage and subsequent diffusion. How can we solve this? Can we find an elegant, original and reliable solution? We believe that the GRACE project will be able to find the answer.

We will develop a smart carrier able to vehicle the GF and release them under specific triggering. We plan to originally exploit, as a trigger, the pH drop caused by active Oc upon bone resorption. We will incorporate the chosen GF in an ad hoc carrier that will be integrated in the scaffold struts, thus avoiding any premature release of the cargo. The GF will stay there until bone remodeling starts with acidic bone resorption, only then, they will be released, in the perfect moment, to stimulate the coupling. The GRACE carriers can also be proposed as a reservoir for drugs, attracting the interest of pharma industries and increasing the grant impact.