Affinity-Controlled Release Systems To Regulate the Response to Acute Kidney Injury
Tuesday, November 14, 2023
1:00 PM-3:00 PM
BIOMED PhD Research Proposal
Title:
Affinity-Controlled Release Systems To Regulate the Response to Acute Kidney Injury
Speaker:
Arielle D’Elia, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisor:
Christopher Rodell, PhD
Assistant Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
Details:
Acute kidney injury (AKI) is a systemic disease that arises in over 50% of critically ill patients, 4 out of 1000 hospitalized children, and is an independent predictor of in-hospital death. Independent of cause, AKI is characterized by a hyperinflammatory milieu that drives progression to chronic kidney disease (CKD). Initial injury is associated with both local and systemic inflammation that precipitate continued renal injury, as well as damage to distant organs (e.g., heart failure, pulmonary fibrosis), making it critical to identify the underlying pathophysiological processes and to develop target therapeutic strategies. The standard of care for AKI aims to prevent further loss of renal function via methods including dialysis to remove blood toxins, increased intake of electrolytes, elimination of nephrotoxic drugs, and reduction of potassium to avoid hyperkalemia. To date, there is currently no FDA approved drug treatment for AKI, as tested drugs such as acetylcysteine and statins have shown inconsistent results. Therefore, there is a critical need to develop treatment strategies that prevent AKI-to-CKD progression.
Regulatory T cells (Tregs) are crucial in transitioning the initial proinflammatory immune response after tissue injury towards a more reparative response. They suppress inflammatory cytokine production and antigen response, therefore creating an environment that prevents continued tissue damage and fosters regeneration. Treg dysfunction, including poor recruitment and differentiation of these cells to the injured kidney, is associated with disease progression.
We aim to develop a locally-deliverable controlled release system that can procure Tregs with appropriate timing, perpetuating a natural transition from required inflammatory to immunoregenerative stages of the tissue healing process. The hydrogel system is composed of an injectable granular hydrogel that leverages physical guest-host interactions for the sustained local presentation of biotherapeutics for T cell recruitment and differentiation. For therapeutic retention, the hydrogel is composed of ‘host’ groups that interact with ‘guest’-modified cytokines allows for local biomolecule release across different time scales through synthetically-tunable hydrogel avidity. Through the delivery of a T cell chemoattractant in conjunction with IL-2 to attract T cells and differentiate them towards a Treg phenotype, respectively, we can harness the immunomodulatory potential of Tregs locally. This approach holds potential to re-shape the functional orientation of the local inflammatory microenvironment, ultimately enabling tissue repair and the attenuation of AKI-to-CKD progression.
Contact Information
Natalia Broz
njb33@drexel.edu