Exosomal mRNAs for Angiogenic-Osteogenic Coupled Bone Repair.
Adv Sci (Weinh)
; 10(33): e2302622, 2023 11.
Article
en 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.
Palabras clave
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
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteogénesis
/
Factor A de Crecimiento Endotelial Vascular
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Adv Sci (Weinh)
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos