Highly Parallel Tissue Grafting for Combinatorial In Vivo Screening

Author:

O’Connor Colleen E.,Neufeld Anna,Fortin Chelsea L.,Johansson Fredrik,Mene Jonathan,Saxton Sarah H.,Simmonds Susana P.,Kopyeva Irina,Gregorio Nicole E.,DeForest Cole A.,Witten Daniela M.,Stevens Kelly R.

Abstract

AbstractMaterial- and cell-based technologies such as engineered tissues hold great promise as human therapies. Yet, the development of many of these technologies becomes stalled at the stage of pre-clinical animal studies due to the tedious and low-throughput nature ofin vivoimplantation experiments. We introduce a ‘plug and play’in vivoscreening array platform called Highly Parallel Tissue Grafting (HPTG). HPTG enables parallelizedin vivoscreening of 43 three-dimensional microtissues within a single 3D printed device. Using HPTG, we screen microtissue formations with varying cellular and material components and identify formulations that support vascular self-assembly, integration and tissue function. Our studies highlight the importance of combinatorial studies that vary cellular and material formulation variables concomitantly, by revealing that inclusion of stromal cells can “rescue” vascular self-assembly in manner that is material-dependent. HPTG provides a route for accelerating pre-clinical progress for diverse medical applications including tissue therapy, cancer biomedicine, and regenerative medicine.

Publisher

Cold Spring Harbor Laboratory

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1. We acknowledge that papers authored by women and scholars from historically excluded racial and ethnic groups are systematically under-cited. So that we are not further perpetuating this problem, we have made every attempt to reference relevant papers in a manner that is equitable in terms of gender and racial representation.

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