EXTRACELLULAR BIOADDITIVES-ADJUVANTED INJECTABLE HYDROGEL SUPPORTS NEOANGIOGENESIS AND DAMPENS ADVERSE CARDIAC REMODELLING

Jun 29, 2022, 2:10 PM
10m
Room: S3 A

Room: S3 A

Speaker

Maiullari, Fabio (Fondazione Istituto Nazionale di Genetica Molecolare, Milan, Italy)

Description

In the last years, the role played by extracellular vesicles (EVs) in inter-cellular and inter-organ communication through the delivery of signal molecules has been revealed and, nowadays, it is considered to be of utmost importance. EVs are secreted by almost all cell types and have an important role in several research fields ranging from oncology to immunology and diagnostics to regenerative medicine. However, the therapeutical employ has not yet been established, although their enormous biological potential is well known. The major limitation to EVs clinical use is the inability to localize the in vivo benefits into strategically defined sites of interest to avoid side effects. Numerous recent discoveries have shown how injectable hydrogels can be used for biomedical applications in regenerative medicine. Specifically, hydrogel-based drug delivery systems are found to be more efficacious than the conventional systemic administration.
Based on these premises, we proposed a new strategy to harness stressed endothelial cell-derived EVs and their angiogenic cargo in injured tissues. EVs, derived from human endothelial cells were collected and used as bioadditives for Gelatin Methacrylate (GelMA) formulation and functionalization. Our results showed that 3D bioprinted structures loaded with EVs support the formation of a functional neovascular network in-situ, constituted of perfused microvessels recapitulating the print pattern. In addition, we assessed the EVs-GelMA effects on cardiac remodeling after acute myocardial infarction (AMI). For this purpose, the EVs-GelMA was injected and polymerized into the ischemic ventricular cardiac wall after the surgical induction of AMI. Results showed improved cardiac performance and a reduction of the ischemic area with partial revascularization of the cardiac wall in the treated animals. Taken together, these findings support the development of new advanced regenerative applications for the revascularization of ischemic organs and peripheral tissues.

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