RT Journal Article T1 Biomimetic Collagen Membranes as Drug Carriers of Geranylgeraniol to Counteract the Effect of Zoledronate A1 Manzano Moreno, Francisco Javier A1 De Luna Bertos, Elvira A1 Toledano Osorio, Manuel A1 Urbano Arroyo, Paula A1 Ruiz Rodríguez, Concepción A1 Toledano Pérez, Manuel A1 Osorio Ruiz, Raquel AB 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. PB MDPI YR 2023 FD 2023-12-22 LK https://hdl.handle.net/20.500.14352/104965 UL https://hdl.handle.net/20.500.14352/104965 LA eng NO Manzano-Moreno FJ, De Luna-Bertos E, Toledano-Osorio M, Urbano-Arroyo P, Ruiz C, Toledano M, et al. Biomimetic Collagen Membranes as Drug Carriers of Geranylgeraniol to Counteract the Effect of Zoledronate. Biomimetics 2023;9:4. https://doi.org/10.3390/biomimetics9010004. NO 2023 Descuento MDPI NO Ministerio de Ciencia, Innovación y Universidades(España) NO Agencia Estatal de Investigación DS Docta Complutense RD 27 abr 2025