ENLIGHT : Light-sensitive Engineered Living Material for acne therapy

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With a prevalence of 250 million people in 2019, acne vulgaris has emerged as the greatest global skin burden and the 8th most prevalent disease worldwide. Acne is a chronic inflammatory disease whose treatment options have important side-effects. For example, antibiotics lead to the development of superbugs. Retinoic acid continues to be the treatment of choice but novel forms of delivery are urgently needed to improve its efficacy and avoid side-effects associated to oral uptake.Our vision is to develop a novel class of Engineered Living Materials (ELMs) for acne treatment. ELMs are "smart" materials that combine living cells with inert matrices. This proposal aims at developing a light-responsive ELM suitable for acne therapy using Bacterial Nanocellulose (BNC) and Optogenetically Engineered Lactococcus lactis to produce retinoic acid in situ. L. lactis is a probiotic Generally Recognised as Safe (GRAS) previously used by the host group in cell engineering. BNC is fully biocompatible, transparent, and with superb mechanical properties. This ELM will allow precise spatiotemporal control using blue light (an orthogonal and non-invasive input that can be easily applied and stopped). The development of this ELM can be fully framed in the Green Chemistry principles, and will take advantage of the synergistic properties of BNC combined with L. lactis engineered to deliver retinoic acid in situ (avoiding its degradation). This blue light-responsive ELM will be a valuable tool in skin treatment, and will be tested in human sebocyte models in the presence of Cutibacterium acnes, a bacterium involved in the pathogenesis of acne condition. Furthermore, this ELM will be very relevant in the treatment of other skin conditions, but also in food industry and cosmetics, as there is broad interest in the precursors of retinoic acid (e.g., beta-carotene, lycopene, vitamin A).