Engineering a multi-therapeutic, 3D-printed scaffold for local immunoprotection and favorable engraftment of pancreatic islets for treatment of type 1 diabetes

Ended Project Grant Awarded Last action

Award ID
F31DK138744
Recipient
Awarding agency
Obligated
$123,874

Award facts

Completion date
Place of performance
Gainesville, FL 32611, USA

Award details come from USAspending.gov.

Description

Abstract
Type 1 diabetes mellitus is an autoimmune disorder in which the patient's pancreatic islets are destroyed by their own immune system, leaving them unable to produce insulin to manage their blood glucose levels. Currently, this disease affects about 1.6 million people in the united states and roughly 180 new patients are diagnosed each day. Clinical islet transplantation is a potential solution that involves injecting donor islets into the patient's liver to secrete insulin and regain blood glucose control. A challenge of this therapy, however, is decreased islet viability due to mechanical stress and adverse inflammation at the infusion site. The utilization of islet encapsulation or islet-loaded porous scaffolds can provide a means to protect islets from these stresses; however, encapsulation can result in insufficient engraftment and incomplete immunosuppression, while traditional scaffold fabrication methods generate inconsistent pores and rough surfaces that can lead to unfavorable and unpredictable host responses to the implant. To address these challenges, this proposal seeks to develop a multi-functional biomaterial scaffold that improves the vascularization, engraftment, and immunoprotection of transplanted pancreatic islets for the treatment of type 1 diabetes mellitus. In aim 1, we will alter scaffold porosity and rung thickness to identify the specific geometric features that will result in robust host engraftment with minimal fibrosis. For aim 2, we will incorporate depots of synergistic immunosuppressants into the 3D-printed scaffold material for controlled local drug delivery. We will characterize the kinetic release curves of the drug eluting scaffold in vitro and optimize the drug loading parameters necessary for sufficient local immune protection. Islet-loaded, therapeutic scaffolds should provide local drug release resulting in the suppression of adverse immune reactions in an allograft RAT transplant model, preventing rejection of the cell cargo. Broadly, results from this work will provide a better understanding of the roles that scaffold geometry and local therapeutic release play in cell-based therapies, while improving experimental outcomes in islet transplantation.

Transactions

Action Obligated Date
Amendment -$8,396
Amendment $44,466
Amendment $43,902
Amendment $43,902
Original award $0

Quick answers

Who received award F31DK138744?

F31DK138744 was awarded to University Of Florida by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on December 26, 2024.

How much is award F31DK138744 worth?

$123,874 has been obligated on F31DK138744.

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