Sustainable synthesis of Hyaluronic Acid via engineered strains of non-pathogenic bacteria - from carbon dioxide and waste feedstock to low-cost, sustainable, and waste-free Hyaluronic Acid for cosmetics, medicine, and nutraceuticals

17Cicada anticipates market entry for its bacterial Hyaluronic Acid (HA) by 2025\. Our projected cumulative 5-year profits are of the order of £5.2 million (by 2029), i.e. 1033% return on investment (ROI) on project costs of £506,366 GBP.

HA is widely distributed throughout connective, epithelial and neural tissues in human and animal bodies. It plays a significant range of biological roles, and is used in cosmetics (e.g. skin-moisturising and wrinkle-reducing products), cosmetic procedures (HA-based dermal fillers), medical treatment (e.g. eye surgery) and effective relief from osteoarthritis (by injecting HA into the joints).

The global market for finished HA products was $20 billion in 2019 (Grand View Research), including $9b for medical products, $8b for cosmetics and $3 billion for nutraceutical products. Despite its chemical simplicity, HA-biochemistry is complex because it interacts differently with cell receptors depending on its molecular weight -- a property which paves the way for more technologically advanced medical products. The market anticipates a growth rate of 7.19% (CAGR) between Y2021-2028, driven mainly by an aging population and increasing aesthetic consciousness.

Commercial HA is sourced from animals (rooster-comb) and competing, fermentation-based, non-animal products. The latter is based on bacterial cultures (especially _Streptococcus equi_) which are human pathogens. Although there is a powerful shift towards non-animal products, the use of human pathogens is problematic due to the immunogenic effect of protein/toxin residuals. This significant drawback can be greater in streptococcal-HA than in animal-sourced HA despite its low overall protein content. **It is therefore anticipated that microbial HA-production will shift towards non-pathogenic bacterial strains**.

**Our vision** is a sustainable, bio-based HA which will spur medical innovation, reduce costs, abolish animal-sourced HA, and expand use of HA into stem cell therapy and tissue engineering. We envisage a revolution where small, digitally controlled HA bioreactors are operated by highly qualified personnel -- producing little or no waste, while consuming carbon and utilising less resource-intensive feedstocks.

**Our key objectives** involve research on two engineered bacterial strains which are non-pathogenic, and which can consume either carbon dioxide or waste feedstocks. **We will focus** on producing HA in continuous production, coupled with robust techno-economic analyses to select the best strain for scale-up.

**Our innovation** is a first-of-a-kind attempt to produce commercial HA via bacterial strains which are non-pathogenic _and_ which consume carbon dioxide and/or less resource-intensive feedstocks -- paving the way for novel nutraceuticals and lower-cost, more circular/sustainable HA-based cosmetic and medical products.