3D-printed bone regeneration scaffolds modulate bone metabolic homeostasis through vascularization for osteoporotic bone defects.
Biomaterials
; 311: 122699, 2024 Dec.
Article
en En
| MEDLINE
| ID: mdl-38981153
ABSTRACT
The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteogénesis
/
Osteoporosis
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Regeneración Ósea
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Ratas Sprague-Dawley
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Neovascularización Fisiológica
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Andamios del Tejido
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Células Madre Mesenquimatosas
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Impresión Tridimensional
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Homeostasis
Límite:
Animals
Idioma:
En
Revista:
Biomaterials
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos