Prevalence of chronic wounds increases along with vascular diseases, diabetes and systemic factors like advanced age. It is estimated that 1-2% of the population would experience a chronic wound and the annual cost of wound care rise to 20 billion dollars in United States. Current therapies are mainly based on in situ administration of bioactive molecules incorporated in wound dressings, although there still are patients resistant to these therapies. In those cases, electroceutical therapies could be an alternative strategy. The use of electrical stimulation is used nowadays to treat neurological and musculoskeletal disorders, although it has a great potential for other tissues as skin. It is known that bioelectricity has an essential role in wound healing, and in chronic wounds, there is a loss of physiological currents. Therefore, the use of exogenous electric fields could enhance chronic wound healing. We propose the use of piezoelectric nanogenerators (NGs) to treat chronic skin ulcers by creating local electric fields without the need of external power and electrodes. Piezoelectric NGs are able to create an inherent electric field when they are strained, collecting the mechanical energy and transforming it to the electric energy. Piezoelectric zinc oxide and poly(vinylidene fluoride) will be tested as NGs for skin tissue applications. We will evaluate their in vitro biocompatibility as well as hemocompatibility and inflammatory properties. The development of in vitro 3D model will allow to analyse the simultaneous interaction of various cell types with NGs. We will also analyse the effect of electric fields generated on different cell types and elucidate the response of the cell membrane and changes in gene expression. Apart from the scientific knowledge, the purpose will allow to start an international multidisciplinary collaboration. The experienced researcher will be able to lead a project and expand his competences and skills in skin tissue engineering.

Malaria remains a serious health concern worldwide, with P. falciparum considered one of the deadliest human parasites. Yet, the currently approved vaccine against malaria (RTS,S/AS01) offers limited protection due to challenges in vaccine development. Using current advances made in understanding immunity to address some of the existing challenges, this proposal aims to develop a more efficacious vaccine against P. falciparum by targeting multiple developmentalstages(sporozoite, liver and blood-stage). In this project, combinations of 1) highly promising whole parasite vaccination approach targeting the liver (late-arresting GAP), 2) RTS,S (provided by GSK) and 3) mRNA versions of clinically evaluated and partially protective blood stage vaccine candidates (Rh5, AMA1-DiCo [sporozoite and blood stage]) will be evaluated in preclinical and small-scale human trials to discern the optimal combination for further clinical investigations. To inform a rational design of future vaccine candidates, CAPTIVATE will analyse the vaccine-induced immune response to acquire a full understanding of malaria protective immunity and develop an advanced immunology in-silico platform. While immunity to blood stage malaria is relatively well understood, the mechanisms of adaptive protective immunity for pre-erythrocytic malaria vaccine candidates are less well-established. CAPTIVATE addresses this critical knowledge gap by combining state-of-the-art preclinical and clinical (CHMI) in vivo malaria vaccine efficacy models with an innovative in-silico platform comprising TCR/VDJ sequencing and artificial intelligence predictions, to identify such mechanisms. CAPTIVATE assembles a unique combination of European experts in their respective fields (malaria modelling in primates, clinical vaccine testing, in-silico modelling of immune responses, innovative omics approaches) in an integrated interdisciplinary approach aimed at bringing the next generation malaria vaccines to the clinic.