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.

筛选可植入生物材料的抗纤维化特性受到体内测试需求的限制。在这里，我们表明，可以通过对化学修饰的水凝胶制剂组合库进行细胞条形码来增加体内筛选的通量。该方法涉及植入藻酸盐制剂的混合物，每种制剂都带有来自不同供体的人脐静脉内皮细胞的条形码，并通过下一代测序对细胞的单核苷酸多态性进行基因分型来关联每种制剂的身份和性能。我们使用该方法筛选了一只小鼠的 20 种藻酸盐制剂和一只非人类灵长类动物的 100 种藻酸盐制剂，并鉴定了三种具有抗纤维化特性的先导水凝胶制剂。用其中一种制剂封装人类胰岛可以在糖尿病小鼠模型中实现长期血糖控制，而用其他两种制剂涂覆医用级导管可以防止纤维化过度生长。体内条形码生物材料的高通量筛选可能有助于确定可增强医疗器械和生物材料封装的治疗细胞的长期性能的配方。