Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA

Kamil Elkhoury, Mo Chen, Polen Koçak, Eduardo Enciso-Martínez, Nicole Joy Bassous, Myung Chul Lee, Batzaya Byambaa, Zahra Rezaei, Yang Li, María Elizabeth Ubina López, Melvin Gurian, Nebras Sobahi, Mohammad Asif Hussain, Laura Sanchez-Gonzalez, Jeroen Leijten, Shabir Hassan, Elmira Arab-Tehrany, Jennifer Ellis Ward, Su Ryon Shin*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)
136 Downloads (Pure)


In additive manufacturing, bioink formulations govern strategies to engineer 3D living tissues that mimic the complex architectures and functions of native tissues for successful tissue regeneration. Conventional 3D-printed tissues are limited in their ability to alter the fate of laden cells. Specifically, the efficient delivery of gene expression regulators (i.e. microRNAs (miRNAs)) to cells in bioprinted tissues has remained largely elusive. In this study, we explored the inclusion of extracellular vesicles (EVs), naturally occurring nanovesicles (NVs), into bioinks to resolve this challenge. EVs show excellent biocompatibility, rapid endocytosis, and low immunogenicity, which lead to the efficient delivery of miRNAs without measurable cytotoxicity. EVs were fused with liposomes to prolong and control their release by altering their physical interaction with the bioink. Hybrid EVs-liposome (hEL) NVs were embedded in gelatin-based hydrogels to create bioinks that could efficiently encapsulate and deliver miRNAs at the target site in a controlled and sustained manner. The regulation of cells’ gene expression in a 3D bioprinted matrix was achieved using the hELs-laden bioink as a precursor for excellent shape fidelity and high cell viability constructs. Novel regulatory factors-loaded bioinks will expedite the translation of new bioprinting applications in the tissue engineering field.

Original languageEnglish
Article number045008
Issue number4
Early online date19 Aug 2022
Publication statusPublished - Oct 2022


  • 3D bioprinting
  • Bioink
  • Extracellular vesicles
  • Liposomes
  • MicroRNAs
  • Tissue regeneration
  • 22/3 OA procedure


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