Biomimetic Collagen Membranes as Drug Carriers of Geranylgeraniol to Counteract the Effect of Zoledronate
Metadatos
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Manzano-Moreno, Francisco Javier; Luna Bertos, María Elvira De; Toledano Osorio, Manuel; Urbano Arroyo, Paula; Ruiz Rodríguez, Concepción; Toledano Pérez, Manuel; Osorio Ruiz, RaquelEditorial
MDPI
Materia
Zoledronate Collagen membranes Osteoblast
Fecha
2023-12-22Referencia bibliográfica
Manzano-Moreno, F.J.; de Luna-Bertos, E.; Toledano-Osorio, M.; Urbano-Arroyo, P.; Ruiz, C.; Toledano, M.; Osorio, R. Biomimetic Collagen Membranes as Drug Carriers of Geranylgeraniol to Counteract the Effect of Zoledronate. Biomimetics 2024, 9, 4. https://doi.org/10.3390/biomimetics9010004
Patrocinador
Grant PID2020-114694RB-I00 funded by MCIN/AEI 10.13039/501100011033; FPU of Ministry of Universities [grant FPU20/00450]Resumen
To counteract the effect of zoledronate and decrease the risk of osteonecrosis of the jaw
(BRONJ) development in patients undergoing guided bone regeneration surgery, the use of geranylgeraniol
(GGOH) has been proposed. Collagen membranes may act as biomimetical drug carriers.
The objective of this study was to determine the capacity of collagen-based membranes doped with
GGOH to revert the negative impact of zoledronate on the growth and differentiation of human
osteoblasts. MG-63 cells were cultured on collagen membranes. Two groups were established:
(1) undoped membranes and (2) membranes doped with geranylgeraniol. Osteoblasts were cultured
with or without zoledronate (50 μM). Cell proliferation was evaluated at 48 h using the MTT colorimetric
method. Differentiation was tested by staining mineralization nodules with alizarin red and
by gene expression analysis of bone morphogenetic proteins 2 and 7, alkaline phosphatase (ALP),
bone morphogenetic proteins 2 and 7 (BMP-2 and BMP-7), type I collagen (Col-I), osterix (OSX),
osteocalcin (OSC), osteoprotegerin (OPG), receptor for RANK (RANKL), runt-related transcription
factor 2 (Runx-2), TGF-β1 and TGF-β receptors (TGF-βR1, TGF-βR2, and TGF-βR3), and vascular
endothelial growth factor (VEGF) with real-time PCR. One-way ANOVA or Kruskal–Wallis and post
hoc Bonferroni tests were applied (p < 0.05). Scanning electron microscopy (SEM) observations were
also performed. Treatment of osteoblasts with 50 μM zoledronate produced a significant decrease in
cell proliferation, mineralization capacity, and gene expression of several differentiation markers if
compared to the control (p < 0.001). When osteoblasts were treated with zoledronate and cultured on
GGOH-doped membranes, these variables were, in general, similar to the control group (p > 0.05).
GGOH applied on collagen membranes is able to reverse the negative impact of zoledronate on the
proliferation, differentiation, and gene expression of different osteoblasts’ markers.