Programmed release of vascular endothelial growth factor and exosome from injectable chitosan nanofibrous microsphere-based PLGA-PEG-PLGA hydrogel for enhanced bone regeneration.
Bone regeneration
Exosome
Sequential delivery
Journal
International journal of biological macromolecules
ISSN: 1879-0003
Titre abrégé: Int J Biol Macromol
Pays: Netherlands
ID NLM: 7909578
Informations de publication
Date de publication:
31 Dec 2023
31 Dec 2023
Historique:
received:
23
03
2023
revised:
31
08
2023
accepted:
03
09
2023
medline:
24
11
2023
pubmed:
7
9
2023
entrez:
6
9
2023
Statut:
ppublish
Résumé
The healing of large bone defects remains a significant challenge in clinical practice. Accelerating both angiogenesis and osteogenesis can promote effective bone healing. In the natural healing process, angiogenesis precedes osteogenesis, providing a blood supply that supports the subsequent progression of osteogenesis. Developing a biomimetic scaffold that mimics the in vivo environment and promotes the proper sequence of vascularization followed by ossification is crucial for successful bone regeneration. In this study, a novel injectable dual-drug programmed releasing chitosan nanofibrous microsphere-based poly(D, l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,l-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel is fabricated by incorporating vascular endothelial growth factor (VEGF) and microspheres loaded with dental pulp stem cells-derived exosomes (DPSCs-Exo). Rapid release of VEGF promotes the swift initiation of angiogenesis, while DPSCs-Exo release ensures persistent osteogenesis. Our results demonstrate that chitosan microsphere-based PLGA-PEG-PLGA hydrogel significantly promotes angiogenesis in human umbilical vascular endothelial cells and enhances the osteogenic differentiation of pre-osteoblasts. Furthermore, in vivo transplantation of this injectable chitosan microsphere-based PLGA-PEG-PLGA hydrogel into calvarial bone defects markedly promotes bone formation. Overall, our study provides a promising approach for improving bone regeneration by temporally replicating the behavior of angiogenesis and osteogenesis.
Identifiants
pubmed: 37673168
pii: S0141-8130(23)03618-8
doi: 10.1016/j.ijbiomac.2023.126721
pii:
doi:
Substances chimiques
polyethylene glycol-poly(lactide-co-glycolide)
0
Vascular Endothelial Growth Factor A
0
Chitosan
9012-76-4
Biocompatible Materials
0
Hydrogels
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
126721Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.