Hydrogel crosslinking mechanisms influence the release and functional delivery of lipid nanoparticles

PEG hydrogels enabled the most tunable mRNA-LNP release kinetics over days, but reduced DiI recovery to about 80%, indicating partial dye leakage from released particles.

• Why it matters: Hydrogel delivery platforms can control antigen availability, yet it remains unclear how distinct crosslinking chemistries affect mRNA-LNP release, stability, and functional delivery.
• What they did: The study compared four crosslinking systems—covalent PEG, ionic alginate, thermoresponsive Poloxamer 407, and Matrigel/collagen—measuring release over days, DiI recovery, particle size distributions, cryoTEM morphology at 37 vs 4, and cellular uptake/transfection.
• The result: All hydrogels released biologically active mRNA-LNPs that mediated protein expression; Matrigel/collagen limited quantitative recovery but released LNPs produced about 80–90% eGFP versus unembedded mRNA-LNPs.

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