Faculty, Staff and Student Publications

Publication Date

7-1-2023

Journal

Nature Biomedical Engineering

DOI

10.1038/s41551-023-01016-2

PMID

37106151

PMCID

PMC10593184

PubMedCentral® Posted Date

7-7-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Screening implantable biomaterials for antifibrotic properties is constrained by the need for in vivo testing. Here we show that the throughput of in vivo screening can be increased by cellularly barcoding a chemically modified combinatorial library of hydrogel formulations. The method involves the implantation of a mixture of alginate formulations, each barcoded with human umbilical vein endothelial cells from different donors, and the association of the identity and performance of each formulation by genotyping single nucleotide polymorphisms of the cells via next-generation sequencing. We used the method to screen 20 alginate formulations in a single mouse and 100 alginate formulations in a single non-human primate, and identified three lead hydrogel formulations with antifibrotic properties. Encapsulating human islets with one of the formulations led to long-term glycaemic control in a mouse model of diabetes, and coating medical-grade catheters with the other two formulations prevented fibrotic overgrowth. High-throughput screening of barcoded biomaterials in vivo may help identify formulations that enhance the long-term performance of medical devices and of biomaterial-encapsulated therapeutic cells.

Keywords

Mice, Animals, Alginates, Hydrogels, Endothelial Cells, Primates, Biocompatible Materials

Published Open-Access

yes

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