The Kinetics of Small Extracellular Vesicle Delivery Impacts Skin Tissue Regeneration

ACS Nano
Helena Henriques-AntunesLino Ferreira

Abstract

Small extracellular vesicles (SEVs) offer a promising strategy for tissue regeneration, yet their short lifetime at the injured tissue limits their efficacy. Here, we show that kinetics of SEV delivery impacts tissue regeneration at tissue, cellular, and molecular levels. We show that multiple carefully timed applications of SEVs had superior regeneration than a single dose of the same total concentration of SEVs. Importantly, diabetic and non-diabetic wounds treated with a single time point dose of an injectable light-triggerable hydrogel containing SEVs demonstrated a robust increase in closure kinetics relative to wounds treated with a single or multiple doses of SEVs or platelet-derived growth factor BB, an FDA-approved wound regenerative therapy. The pro-healing activity of released SEVs was mediated at the tissue/cell level by an increase in skin neovascularization and re-epithelization and at the molecular level by an alteration in the expression of 7 miRNAs at different times during wound healing. This includes an alteration of has-miR-150-5p, identified here to be important for skin regeneration.

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Citations

Nov 16, 2019·Angewandte Chemie·Josephine BlerschLino Ferreira
Apr 28, 2020·Advanced Healthcare Materials·Xin ZhengDavid L Kaplan
Jun 3, 2020·Nature Reviews. Cardiology·Ricardo Cerqueira de AbreuLino Ferreira
Jul 28, 2020·International Journal of Molecular Sciences·Wei HuYong Zhao
Sep 22, 2020·Advanced Functional Materials·Meadhbh Á BrennanDavid J Mooney
Oct 8, 2020·Cells·Marija PetkovicLouise Torp Dalgaard
Dec 12, 2020·Advanced Science·Britta F HettichJean-Christophe Leroux
Jan 18, 2021·Acta Biomaterialia·Vishnu Priya Murali, Christina A Holmes
Feb 7, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Yiyao ZhangXifan Mei
Dec 1, 2020·Frontiers in Bioengineering and Biotechnology·Xige ZhaoQiang Yang
Sep 25, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kevin Las HerasRosa Maria Hernandez
Apr 20, 2021·Advanced Drug Delivery Reviews·Anika NagelkerkeMolly M Stevens
May 9, 2021·Advanced Drug Delivery Reviews·Dominik BuschmannJames Brian Byrd
Jun 3, 2021·International Journal of Molecular Sciences·Hee Sook HwangSun Hwa Kim
Jun 30, 2021·Clinical and Translational Medicine·Xiaoyun HeChunlin Ou
Aug 11, 2021·ACS Nano·Yongping LiangBaolin Guo
Aug 12, 2021·Journal of Extracellular Vesicles·Ricardo C de AbreuLino Ferreira
Nov 19, 2021·Journal of Nanobiotechnology·Yuan DingWeilin Wang

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