Therapeutic Strategies Targeting Cariogenic Biofilm Microenvironment

Cariogenic biofilms are highly structured microbial communities embedded in an extracellular matrix, a multifunctional scaffold that is essential for the existence of the biofilm lifestyle and full expression of virulence. The extracellular matrix provides the physical and biological properties that enhance biofilm adhesion and cohesion, as well as create a diffusion-modulating milieu, protecting the resident microbes and facilitating the formation of localized acidic pH niches. These biochemical properties pose significant challenges for the development of effective antibiofilm therapeutics to control dental caries. Conventional approaches focusing solely on antimicrobial activity or enhancing remineralization may not achieve maximal efficacy within the complex biofilm microenvironment. Recent approaches disrupting the biofilm microbial community and the microenvironment have emerged, including specific targeting of cariogenic pathogens, modulation of biofilm pH, and synergistic combination of bacterial killing and matrix degradation. Furthermore, new "smart" nanotechnologies that trigger drug release or activation in response to acidic pH are being developed that could enhance the efficacy of current and prospective chemical modalities. Therapeutic strategies that can locally disrupt the pathogenic niche by targeting the biofilm structure and its microenvironment to eliminate the embedded microorganism and facilitate the action of remineralizing agents may lead to enhanced and precise anticaries approaches.