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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PRINT-AID (Multidisciplinary European training network for development of personalized anti-infective medical devices combining printing technologies and antimicrobial functionality)

Teaser

Summary

According to ECDC, over 4 million healthcare-associated infections in the EU cause 37,000 deaths and cost EUR 7 billion per annum. Half of these infections are related to medical devices of which vast majority (80%) is further related to bacterial biofilms. Thus, strategies to prevent medical device related infections, either through control of bacterial growth or prevention of biofilm formation on medical device, are urgently needed to tackle the high prevalence and cost healthcare associated infections.

PRINT-AID is and interdisciplinary training network aiming to tackle the health-care associated infections at multiple level. PRINT-AID aims to educate next generation scientist in an innovative research program in the areas of antimicrobial drug discovery, additive manufacturing, animal infection models related to bacterial biofilms and medical devices and data integration and standardization. The project aims to establish a collection of novel anti-microbial and anti-biofilm compounds and anti-biofim formulations that can be used to combat biofilm related infections. PRINT-AID aims to establish more relevant preclinical models for medical device related infections and using these models study the protective effect of the designed anti-biofilm formulations. PRINT-AID further aims to establish guidelines for standardization of biofilm-related assays.

Work performed

To accomplish these ambitious aims, PRINT-AID consortium brings together 12 participants (of which 5 industrial) from EU and US with expertise in various disciplines ranging from anti-microbial drug discovery, 3D printing, animal infection models and data integration and standardization. Nine early-stage-researchers are trained within the network to become experts within these disciplines by academic and industrial partners.
The scientific efforts of the PRINT-AID consortium are structured in four work packages and aim towards 1) identification and characterization of novel anti-microbial compounds with anti-biofilm activity (WP1) 2) development of the anti-microbial formulations and further prototypic medical devices using state-of-the-art printing technologies (WP2) and 3) investigation of the anti-microbial activity of the printed devices and formulations in preclinical infection models (WP3). Additionally, data standardization and integration is performed (WP4).
During the reporting period the activities carries out in WP1 resulted in identification of several anti-microbial compounds with potential for further development for formulation. These compounds show wide chemical diversity in terms of parent structures and chemical properties and show favorable characteristics as leads for 3D printing. WP2 has produced scaffolds and microparticle systems for encapsulation of anti-microbial leads as well as development on the 3D printing manufacturing process itself. These improvements include several adaptations to the existing 3D printer and allow the required high accuracy for the printing of the prototype devices. WP3 has established several novel preclinical models amenable for the evaluation of the in vivo anti-microbial and anti-biofilm activity of the 3D printed devices. These model several commonly used medical devices of the healthcare sector. WP4 has produced minimum information guidelines for biofilm experiments and manual for standardized methods for biofilm experiments.
The training efforts taken by the consortium include organization of two network-wide events, one workshop and one summer school including hands-on-training in additive manufacturing techniques, including 3D printing. Two early-stage-researchers have undertaken secondment periods, with total duration of 10,5 months. Additionally, one online-course is made available for the early-stage-researchers by the consortium.

Final results

The innovative research programme of PRINT-AID project has progressed beyond state-of-the-art on several research fields. Novel lead compounds and compounds combinations are identified that act as anti-microbials and anti-biofilm. This is significant, as historically the vast majority of anti-microbial drug discovery has focused on planktonic bacteria while in reality infections, and especially chronic infections are associated with bacterial biofilms. As biofilms are often resistant to current anti-microbials drugs there is urgent need to identify novel leads specifically targeting bacterial biofilms. As relevant is the implementation and utilization of standardized methodology to study the lead compounds anti-biofilm effect. Furthermore, the project identifies innovative formulations for the anti-biofilm leads based on 3D printing technology. The use of 3D printing for the manufacturing of the protype medical devices offers a tool box for further development of personalized anti-infective medical devices. Additionally, technological improvements on the 3D printer itself is expected. Novel preclinical models developed during the project enable the testing of the anti-infective capacity of the formulations. Altogether these scientific and training efforts are expected to deliver a proof-of-concept for an anti-infective medical device capable of resisting biofilm infections with proven in vivo activity. To tackle fragmentation in the respective research fields PRINT-AID educates nine early stage researchers capable of acting as experts not only in their specific field but with understanding of the involved disciplines. PRINT-AID has established new connections to parallel EU-funded projects with the potential to increase synergyto the field.