{
  "abstract": "Regulatory T cells (Tregs) are key mediators of immune resolution and tissue repair following acute kidney injury (AKI), yet strategies to selectively enrich Tregs within the renal microenvironment remain limited. Interleukin-2 (IL-2) is essential for Treg survival and function, but systemic IL-2 delivery is constrained by a short half-life, narrow therapeutic window, and risk of off-target activation of cytotoxic T cells. Effective Treg-based immunomodulation may therefore require both localized cytokine signaling and targeted recruitment of precursor immune populations. Here, we present a sequential, biomaterial-based immunomodulatory strategy that integrates immune cell recruitment with sustained cytokine delivery. An injectable granular hydrogel physically encapsulating the chemokine CCL21 was used to initially recruit CD4+ T cells to the injured kidney. Subsequently, supramolecular guest-host interactions were leveraged to deliver IL-2 modified with the hydrophobic \"guest\" moiety adamantane, enabling prolonged local cytokine release over 28 days. In healthy mice, we observed early CD4+ T cell recruitment, followed by a pronounced increase in Treg frequency, consistent with immune reprogramming driven by our sequential delivery system. In a murine model of bilateral ischemia-reperfusion (BiAKI), this injectable biomaterial induced a local increase in the proportion of FOXP3-expressing Tregs and a concomitant decrease in the levels of AKI markers. This two-step immunomodulatory approach minimizes acute immune activation while promoting long-term enrichment of Tregs within the renal microenvironment. Together, these findings demonstrate that granular hydrogels with supramolecular host capability can orchestrate immune recruitment and differentiation in a spatiotemporally controlled manner, providing a versatile immunomodulatory platform for applicability in kidney disease.",
  "abstract_shown": true,
  "affiliations": [
    "School of Biomedical Engineering and Sciences, Drexel University, Philadelphia, PA, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "A. M. D'Elia"
    },
    {
      "name": "K. M. Kim"
    },
    {
      "name": "A. Shaw"
    },
    {
      "name": "S. Gholampoor"
    },
    {
      "name": "J. Friedrich"
    },
    {
      "name": "C. R. Russell"
    },
    {
      "name": "A. J. Seiner"
    },
    {
      "name": "A. R. Osidach"
    },
    {
      "name": "A. L. McSweeny"
    },
    {
      "name": "W. Gao"
    },
    {
      "name": "E. Adolay"
    },
    {
      "name": "S. Lynch"
    },
    {
      "name": "A. Stergar"
    },
    {
      "name": "E. Rajadhyaksha"
    },
    {
      "name": "B. Sarkar"
    },
    {
      "name": "D. E. Soranno"
    },
    {
      "affs": [
        0
      ],
      "name": "C. B. Rodell"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cw78h93ra7y55.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.30.755753",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755753v1.full",
  "id": "cw78h93ra7y55",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755753v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioengineering"
    ],
    [
      "openalex",
      "1313|Hydrogels: synthesis, properties, applications"
    ]
  ],
  "openalex": "W7215678772",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755753v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cw78h93ra7y55.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:46Z",
      "native_id": "10.64898/2026.09.30.755753",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755753v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Avidity-controlled biotherapeutic delivery systems for the treatment of ischemia-reperfusion acute kidney injury",
  "title_text": "Avidity-controlled biotherapeutic delivery systems for the treatment of ischemia-reperfusion acute kidney injury",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:46Z",
  "url": "https://research.draconitic.com/paper/cw78h93ra7y55",
  "venue": "bioRxiv",
  "versions": []
}