Exosomal mRNAs for Angiogenic-Osteogenic Coupled Bone Repair.
Adv Sci (Weinh)
; 10(33): e2302622, 2023 11.
Article
em En
| MEDLINE
| ID: mdl-37847907
ABSTRACT
Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic-osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.
Palavras-chave
PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel; bone morphogenetic protein 2 (BMP-2) mRNAs coupled angiogenic-osteogenic regeneration; small extracellular vesicles carrying therapeutic mRNAs and associated microRNAs; track-etched membrane-based nanoelectroporation (TM-nanoEP); vascular endothelial growth factor A (VEGF-A)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Fator A de Crescimento do Endotélio Vascular
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article