Injectable Therapeutic Organoids Using Sacrificial Hydrogels

Summary

Organoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing self-organized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. As cell therapy transforms into a new class of therapeutic modality, this simple method—by making use of the dynamic nature of hydrogels—could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.

Graphical Abstract

Highlights

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  Therapeutic, prevascularized organoids were formed in a sacrificial scaffold

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  The organoids are highly reproducible and grown in a high-throughput manner

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  The organoids rapidly formed perfusing vasculature in healthy mice

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  Therapeutic potential was assessed in a mouse model of peripheral artery disease

Abstract

Biotechnology; Bioelectronics; Biomaterials