한빛사논문
Sudip Mukherjee1,7,9, Boram Kim 1,9, Lauren Y. Cheng 1,9, Michael David Doerfert1, Jiaming Li 1, Andrea Hernandez1, Lily Liang 1, Maria I. Jarvis1, Peter D. Rios2, Sofia Ghani2, Ira Joshi2, Douglas Isa2, Trisha Ray3, Tanguy Terlier4, Cody Fell1, Ping Song1, Roberto N. Miranda 5, Jose Oberholzer6, David Yu Zhang 1,8 & Omid Veiseh 1
1Department of Bioengineering, Rice University, Houston, TX, USA.
2CellTrans, Inc., Chicago, IL, USA.
3Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
4SIMS Laboratory, Shared Equipment Authority, Rice University, Houston, TX, USA.
5Department of Hematopathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
6Division of Transplant Surgery, University of Virginia, Charlottesville, VA, USA.
7Present address: School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, India.
8Present address: NuProbe USA, Houston, TX, USA.
9These authors contributed equally: Sudip Mukherjee, Boram Kim, Lauren Y. Cheng.
Corresponding authors : Correspondence to David Yu Zhang or Omid Veiseh.
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.
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