Preprint
Avidity-controlled biotherapeutic delivery systems for the treatment of ischemia-reperfusion acute kidney injury
bioRxiv
01 Oct 2026
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.
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Details
- Title
- Avidity-controlled biotherapeutic delivery systems for the treatment of ischemia-reperfusion acute kidney injury
- Creators
- Arielle M. D'EliaKenneth M. Kim - Drexel UniversityAlleé Shaw - Indiana University – Purdue University IndianapolisSayeh Gholampoor - Indiana University – Purdue University IndianapolisJessica Friedrich - Indiana University – Purdue University IndianapolisCarl R. Russell - Indiana University – Purdue University IndianapolisAkari J. Seiner - Drexel UniversityAlexander R. Osidach - Drexel UniversityAbigail L. McSweeny - Drexel UniversityWinni Gao - Drexel UniversityEmma Adolay - Indiana University – Purdue University IndianapolisSarah Lynch - Indiana University – Purdue University IndianapolisAngus Stergar - Indiana University – Purdue University IndianapolisEvan Rajadhyaksha - Indiana University – Purdue University IndianapolisBiplab Sarkar - Drexel UniversityDanielle E. Soranno - Purdue University West LafayetteChristopher B. Rodell - Drexel University
- Publication Details
- bioRxiv
- Publisher
- Cold Spring Harbor Laboratory
- Edition
- 1.1
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- School of Biomedical Engineering and Science
- Other Identifier
- 991022237383304721