Screening hydrogels for antifibrotic properties by implanting cellularly barcoded alginates in mice and a non-human primate.

Autor: Mukherjee S; Department of Bioengineering, Rice University, Houston, TX, USA.; School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, India., Kim B; Department of Bioengineering, Rice University, Houston, TX, USA., Cheng LY; Department of Bioengineering, Rice University, Houston, TX, USA., Doerfert MD; Department of Bioengineering, Rice University, Houston, TX, USA., Li J; Department of Bioengineering, Rice University, Houston, TX, USA., Hernandez A; Department of Bioengineering, Rice University, Houston, TX, USA., Liang L; Department of Bioengineering, Rice University, Houston, TX, USA., Jarvis MI; Department of Bioengineering, Rice University, Houston, TX, USA., Rios PD; CellTrans, Inc., Chicago, IL, USA., Ghani S; CellTrans, Inc., Chicago, IL, USA., Joshi I; CellTrans, Inc., Chicago, IL, USA., Isa D; CellTrans, Inc., Chicago, IL, USA., Ray T; Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA., Terlier T; SIMS Laboratory, Shared Equipment Authority, Rice University, Houston, TX, USA., Fell C; Department of Bioengineering, Rice University, Houston, TX, USA., Song P; Department of Bioengineering, Rice University, Houston, TX, USA., Miranda RN; Department of Hematopathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Oberholzer J; Division of Transplant Surgery, University of Virginia, Charlottesville, VA, USA., Zhang DY; Department of Bioengineering, Rice University, Houston, TX, USA. genomic.dave@gmail.com.; NuProbe USA, Houston, TX, USA. genomic.dave@gmail.com., Veiseh O; Department of Bioengineering, Rice University, Houston, TX, USA. omid.veiseh@rice.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2023 Jul; Vol. 7 (7), pp. 867-886. Date of Electronic Publication: 2023 Apr 27.
DOI: 10.1038/s41551-023-01016-2
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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