Human milk oligosaccharide conjugated dendritic polyglycerols as mucus-mimetic barriers for bacterial inhibition

Mucin glycoproteins play a vital role in body’s defense system yet remain underexplored due to their structural complexity and tendency to crosslink. Animal-derived mucins feature non-human glycosylation whilst synthetic mucin-mimetics often lack the structural diversity found in natural glycosylation. We report on a synthetic mucin-mimetic that employs carbohydrates derived from human milk presenting diverse and complex carbohydrates. We functionalized dendritic polyglycerol (dPG) with human milk oligosaccharides (HMOs) and redox-sensitive crosslinking domains to replicate mucus. Two molecular weight variations of dendritic polyglycerol conjugates were prepared (MW = 10 kDa and 550 kDa) and interconnected via disulfide bond with polyethylene glycol dithiol linker (PEG-2SH). The resultant hydrogels resemble mucus and demonstrate tunable viscoelastic properties. At 4-5% w/v, these properties are analogous to those observed in healthy human sputum. dPG-HMOs demonstrate inhibitory activity against Pseudomonas aeruginosa . dPG-HMO hydrogels enhance the natural ability of HMOs to inhibit biofilm formation showing that these conjugate materials have potential as a topical antiseptic or bioactive gel.