Promicrobial mucoadhesive micro-composites enable delivery of beneficial oral bacteria to restore and modulate oral biofilm communities.

Imbalances within the oral microbiome, composed of over 700 phylotypes, drive both local diseases, including periodontitis, and systemic conditions, such as rheumatoid arthritis and cardiovascular disease. Given the overuse of conventional antimicrobial agents to manage oral diseases and the relapsing nature associated with current intervention strategies, innovative promicrobial approaches to oral biofilm community restoration are needed. Importantly, there is a critical unmet clinical need for active restoration and sustained delivery of beneficial oral commensals rather than continued disruption of already-imbalanced communities. We have developed a promicrobial formulation encapsulating live, health-associated, oral bacteria within mucoadhesive micro-composites to promote the establishment of beneficial biofilms under simulated oral flow conditions. We encapsulated and characterised a five-species bioactive consortia of oral bacteria in alginate micro-composites, surface modified with poly-l-lysine to enhance their adhesion to artificial saliva-coated surfaces in vitro. Dissemination of the encapsulated bacteria from the micro-composites led to the formation of stable oral biofilms. Notably, biofilm composition could be modulated by altering the encapsulated bioactive composition, enabling a tailored and targeted pathway to biofilm restoration. Under representative saliva flow, delivery of bioactives following their bioencapsulation resulted in strong biofilm-forming capacity, even in the presence of pre-existing oral bacterial communities containing pathobionts, highlighting their potential clinical applications in dental biofilm bioengineering. In experiments designed to simulate periodontal pocket debridement, we observed immunomodulation following treatment with bioactive formulations and pathobiont reduction when Limosilactobacillus reuteri was also incorporated into the consortia. These findings establish a framework for using sustained-release encapsulated probiotics to modulate the oral microbiome, offering a paradigm shift towards biofilm-promoting therapies for oral healthcare and paving the way for oral microbiome transplantation.