The concept behind MOZART is to develop a library of inorganic nanomatrices to be used as smart platforms for effective, non-invasive and highly targeted therapies. MOZART will address, as proof of concept, nanomatrices to treat delayed bone healing and non-healing chronic skin wounds, which are both characterised by an inflammation and often infection. Mesoporous therapeutic glasses (MTGs), doped with selected ions (e.g. Ag+, Li+, Cu2+, Sr2+, Ce3+, B3+) and having nanopores of adjustable size within 2-50 nm, will be synthesised and then loaded with the chosen payload. Ordered mesoporous carbons (OMCs) will also be manufactured to host a wide range of biomolecules and higher payload. As in an orchestra, where the integration among the different participants allows a harmonious symphony to be created, in MOZART the synergistic release of ions and drugs will be directed to achieve a radically improved therapeutic effect. The exploitation of the response of self-immolative polymer coatings upon pH changes will be used as an elegant and effective way for triggering the payload release. The (coated) nanomatrices will be incorporated in a thermosensitive gel that is liquid at room temperature and undergoes sol-gel transition in the physiological environment. These gels are perfect candidates to develop non-invasive procedures to introduce MOZART nanomatrices to the pathological site and keep them in place for the required time. Clinical and societal impacts of MOZART will be enormous, considering the extraordinarily high number of pathological cases potentially involved. Only in EU, 350 000 patients per year are affected by non-union bone fractures and 2.2 million people suffer from chronic wounds. We expect that MOZART approaches will significantly reduce the healing time of non-union bone fractures (within 4 months vs. a minimum of 12 months) and will allow at least 50% of people suffering from chronic wounds to heal fully.

Cardiac disease remains a major societal and healthcare burden that affect nearly two million European citizens every year. The REBORN project brings together a consortium of six scientific, four SME, and two large company partners who are committed to making a step-change to the development of medical devices for cardiac applications for the treatment of people who have suffered from a heart attack (myocardial infarction, MI). A MI causes fibrosis in the heart walls, which impedes cardiac function and means there is a high risk of subsequent heart failure post-MI. There are no current treatment options to address this major clinical problem. The REBORN project will use smart and multifunctional biomaterials to deliver a new medical device in the form of a cardiac patch, to be applied to the heart in order to stimulate and support local heart tissue remodelling. The piezoelectric patch will electromechanically couple with the heart and deliver anti-inflammatory, anti-fibrotic and cardiomyocyte proliferative factors on demand, with drug release triggered by ultrasonic (US) stimulation from outside the body. Development of the device will be based on new smart multifunctional materials: electrospun piezoelectric fibres combined with smart carriers designed to work in harmony with the US. To prepare the ground for exploitation, the patch will be extensively characterised in vitro and in vivo. Accelerating the development of the patch requires an effective in vitro model for experimentation, and novel 3D bioprinting techniques will be exploited to create a 3D in vitro model in the form of a tissue engineered tubular heart chamber, capable of pumping fluid using cell contractile forces. This will give a new in vitro model capable of both functional and structural testing. The REBORN project will develop, validate and prepare for the exploitation new treatment options for post-MI fibrosis and new processes for cardiac therapy development, addressing major unmet cli