{
  "abstract": "Hydrogels have emerged as attractive vaccine delivery platforms because they enable controlled modulation of antigen availability. However, how different hydrogel environments affect the release and functionality of mRNA-loaded lipid nanoparticles (mRNA-LNPs) remains poorly understood. Here, we investigated the release, stability, cellular uptake, and transfection capability of LNPs released from four hydrogel systems representing distinct crosslinking mechanisms: covalently crosslinked poly(ethylene glycol) (PEG), ionically crosslinked alginate, thermoresponsive Poloxamer 407 (P407), and protein-based Matrigel/collagen hydrogels. All hydrogel types enabled release of LNPs over days, with lower polymer concentrations generally exhibiting faster nanoparticle release. PEG offered greatest tunability of release kinetics; at the same time the recovery of the LNP-incorporated fluorescent dye DiI was reduced to about 80 %, indicating partial dye leakage. Alginate hydrogels exhibited recovery of DiI below 50 % and broader particle size distributions after release, while P407 hydrogels largely preserved LNP characteristics. CyroTEM analysis revealed that mRNA-LNPs kept at 37 , including those released from hydrogels, exhibited a more compact and electron-dense morphology than mRNA LNPs maintained at 4 . Notably, although quantitative recovery from Matrigel/collagen hydrogels was limited, released LNPs achieved approximately 80-90 % of the eGFP expression compared to mRNA-LNPs that have not been embedded. Importantly, cellular uptake and transfection experiments demonstrated that all investigated hydrogels released biologically active mRNA-LNPs capable of mediating protein expression. Moreover, our findings show that hydrogel composition is a critical determinant of mRNA-LNP release, stability, functional delivery and morphology of the released particles. This work provides design principles for the development of hydrogel-based mRNA delivery systems aimed at sustained antigen availability and prolonged vaccine responses.",
  "abstract_shown": true,
  "affiliations": [
    "University of Regensburg"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "A. G. Schreiber"
    },
    {
      "name": "F. Hauswirth"
    },
    {
      "name": "L. Reger"
    },
    {
      "name": "S. P. Carneiro"
    },
    {
      "name": "O. M. Merkel"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Breunig"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9f8fm06f7btmt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.13.741169",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.13.741169v2.full",
  "id": "9f8fm06f7btmt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.13.741169v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "1312|RNA Interference and Gene Delivery"
    ]
  ],
  "openalex": "W7203634432",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.13.741169v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9f8fm06f7btmt.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:20:53Z",
      "native_id": "10.64898/2026.08.13.741169",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.13.741169v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Hydrogel crosslinking mechanisms influence the release and functional delivery of lipid nanoparticles",
  "title_text": "Hydrogel crosslinking mechanisms influence the release and functional delivery of lipid nanoparticles",
  "type": "preprint",
  "updated_at": "2026-11-04T00:21:15Z",
  "url": "https://research.draconitic.com/paper/9f8fm06f7btmt",
  "venue": "bioRxiv",
  "versions": []
}