Engineered Delivery of Dental Stem-Cell-Derived Extracellular Vesicles for Periodontal Tissue Regeneration.

Autor: Zarubova J; Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA, 90095-1600, USA.; Department of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences, Prague, 14220, Czech Republic., Hasani-Sadrabadi MM; Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA, 90095-1600, USA., Dashtimoghadam E; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-3290, USA., Zhang X; Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA, 90095-1600, USA., Ansari S; Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, CA, 90095, USA., Li S; Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA, 90095-1600, USA., Moshaverinia A; Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, CA, 90095, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2022 Jun; Vol. 11 (12), pp. e2102593. Date of Electronic Publication: 2022 Mar 04.
DOI: 10.1002/adhm.202102593
Abstrakt: Periodontal disease begins as an inflammatory response to a bacterial biofilm deposited around the teeth, which over time leads to the destruction of tooth-supporting structures and consequently tooth loss. Conventional treatment strategies show limited efficacy in promoting regeneration of damaged periodontal tissues. Here, a delivery platform is developed for small extracellular vesicles (sEVs) derived from gingival mesenchymal stem cells (GMSCs) to treat periodontitis. EVs can achieve comparable therapeutic effects to their cells of origin. However, the short half-lives of EVs after their administration along with their rapid diffusion away from the delivery site necessitate frequent administration to achieve therapeutic benefits. To address these issues, "dual delivery" microparticles are engineered enabling microenvironment-sensitive release of EVs by metalloproteinases at the affected site along with antibiotics to suppress bacterial biofilm growth. GMSC sEVs are able to decrease the secretion of pro-inflammatory cytokines by monocytes/macrophages and T cells, suppress T-cell activation, and induce the formation of T regulatory cells (Tregs) in vitro and in a rat model of periodontal disease. One-time administration of immunomodulatory GMSC sEV-decorated microparticles leads to a significant improvement in regeneration of the damaged periodontal tissue. This approach will have potential clinical applications in the regeneration of a variety of tissues.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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