Project Portugal 2030

Summary

The aim of the MATreSS project is to develop bespoke biodegradable fibres with improved functionality suitable for weaving into wound dressings for the treatment of skin burns. This is attained by dispersing drug-loaded, highly porous silicon nanoparticles within a fibre matrix material during a tailored microfluidic fabrication, which will be used to weave wound dressing materials. This will ultimately lead to improving the dressings’ therapeutic efficacy and customizing the drug release profile according to individual clinical needs of burn patients. To address this aim, the project is organised in 5 work packages (WPs), with individualized objectives and milestones. WP1 will deal with Project management and financing. In WP2 we will develop, optimise and characterise methods for the preparation of porous silicon nanoparticles (pSiNs), based on the reduction reaction of silica with Mg, to obtain pharmaceutical-grade materials displaying high drug-loading capacity and homogenous size and porosity. We will then assess the pSiNs’ performance in the context of biological compatibility (with human skin fibroblasts), biodegradability and in vitro drug release of two loaded miRNAs (miR-425-5p, which promotes regenerative skin repair and miR 302b, which regulates NF-kB activation upon bacterial infection) with the objective of attaining nanoparticles with tuneable biodegradation rate and harmless biodegradation products. In WP3 we will devise strategies for uniform pSiNs dispersion in the polymer matrix, while maintaining the activity of the loaded compounds without leaching from the polymer. To accomplish this, we will design a microfluidic device for fibre manufacture using a polydimethylsiloxane (PDMS) flow-focusing device in which the selection of the geometrical microfluidic cross-section is optimised with the objective of obtaining circular or flat PLGA and PLA polymer composite fibres. In this WP will also map the effect of flow, rheological and other experimental conditions on the spun fibres with the objective of, for the first time, obtaining fibre composites manufactured through microfluidics which can concomitantly carry two miRNAs modulating bacterial infection and wound healing. Then, in WP4, the validation of the fibre material in a human ex vivo wound healing model will be conducted. Human skin samples, obtained as waste material from surgical procedures such as abdominal and breast reduction will be collected and cultured in appropriate media, which will then be covered for a period of time with the composite dressings and investigated for genes known to be involved in the wound healing process by PCR analysis and immunocytochemistry, followed by validation using antibodies against proteins involved in the healing process. These studies will underpin the translation of the most promising wound dressing material to the in vivo models, where their impact will be evaluated in a burn wound healing mouse model. In WP5 the selected dressings will be used to cover skin grafts in the burn wound of the mouse model followed by RNA isolation and qPCR of the cells in and around the burn wound to look for markers of wound regeneration. This will be implemented by first induced a burn injury in explanted human skin, which will subsequently be grafted onto the skin of immunocompromised mice. The objective here is to pre-clinically validate our dressings as a medical material, suitable for use in the operating theatre for burn patients.