Development of a Mucoadhesive Hydrogel for Biofilm Oral Microbiota Transplants

Objectives: Oral microbiota transplant (OMT) holds the promise to restore oral microbiome homeostasis in patients with oral dysbiosis or infections. Widespread clinical implementation of OMT is limited by the lack of effective microbial delivery platforms. Current delivery platforms do not take advantage of the enhanced physical adhesion and metabolic activity of biofilms, ultimately limiting their efficacy. Therefore, the objective of this research is to develop a hydrogel that can be used in a delivery platform to exploit the advantages of biofilm in OMT.
Methods: The proposed delivery system consists of two parts: first, a mucoadhesive hydrogel that engrafts onto the oral mucosa and second, a carrier bead that supports microbial biofilm growth. Mucoadhesive properties of hydrogel formulations consisting of calcium chloride crosslinked alginate and carboxymethyl cellulose (CMC) were characterized using rheology and verified using an in vitro flow model over porcine esophageal tissue. Biofilms of probiotics Streptococcus salivarius and Levilactobacillus brevis were then grown on agar beads andloaded into the hydrogels. Biofilms were qualitatively and quantitatively assessed using scanning electron microscopy (SEM) and colony forming unit (CFU) assay, respectively.
Results: Measured ratios of loss and storage modulus (tan δ) suggests that the mechanical strength of the alginate/CMC hydrogel is primarily derived from the alginate-Ca²⁺ network (lowest tan δ for alginate alone). Estimations based on rheological synergism suggests hydrogel spreadability, surface coverage and mucoadhesive properties are proportional to CMC concentrations, which were also confirmed using in vitroflow system. Finally, the hydrogel composition also showed biocompatibility with Streptococcus salivarius and Levilactobacillus brevis as the SEM images and CFU assays showed stable and reproducible biofilm growth on the beads within the hydrogel.
Conclusions: This research demonstrates that the proposed hydrogel can provide intimate contact with the mucosal surface and harness the advantages of biofilm for OMT.