{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:04:38Z","timestamp":1792803878029,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MCIN\/AEI 10.13039\/501100011033","award":["PID2020-114694RB-I00"],"award-info":[{"award-number":["PID2020-114694RB-I00"]}]},{"name":"MCIN\/AEI 10.13039\/501100011033","award":["FPU20\/00450"],"award-info":[{"award-number":["FPU20\/00450"]}]},{"name":"FPU of Ministry of Universities","award":["PID2020-114694RB-I00"],"award-info":[{"award-number":["PID2020-114694RB-I00"]}],"id":[{"id":"https:\/\/ror.org\/03zcny908","id-type":"ROR","asserted-by":"crossref"}]},{"name":"FPU of Ministry of Universities","award":["FPU20\/00450"],"award-info":[{"award-number":["FPU20\/00450"]}],"id":[{"id":"https:\/\/ror.org\/03zcny908","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomimetics"],"abstract":"<jats:p>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 \u03bcM). 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-\u03b21 and TGF-\u03b2 receptors (TGF-\u03b2R1, TGF-\u03b2R2, and TGF-\u03b2R3), and vascular endothelial growth factor (VEGF) with real-time PCR. One-way ANOVA or Kruskal\u2013Wallis and post hoc Bonferroni tests were applied (p &lt; 0.05). Scanning electron microscopy (SEM) observations were also performed. Treatment of osteoblasts with 50 \u03bcM zoledronate produced a significant decrease in cell proliferation, mineralization capacity, and gene expression of several differentiation markers if compared to the control (p &lt; 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 &gt; 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\u2019 markers.<\/jats:p>","DOI":"10.3390\/biomimetics9010004","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T01:19:42Z","timestamp":1703207982000},"page":"4","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Biomimetic Collagen Membranes as Drug Carriers of Geranylgeraniol to Counteract the Effect of Zoledronate"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3176-7613","authenticated-orcid":false,"given":"Francisco Javier","family":"Manzano-Moreno","sequence":"first","affiliation":[{"name":"Biomedical Group (BIO277), Department of Stomatology, School of Dentistry, University of Granada, 18071 Granada, Spain"},{"name":"Instituto Investigaci\u00f3n Biosanitaria, ibs. Granada, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4381-5942","authenticated-orcid":false,"given":"Elvira","family":"de Luna-Bertos","sequence":"additional","affiliation":[{"name":"Instituto Investigaci\u00f3n Biosanitaria, ibs. Granada, 18012 Granada, Spain"},{"name":"Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Toledano-Osorio","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Granada, Colegio M\u00e1ximo de Cartuja s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Urbano-Arroyo","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Granada, Colegio M\u00e1ximo de Cartuja s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4332-6812","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Instituto Investigaci\u00f3n Biosanitaria, ibs. Granada, 18012 Granada, Spain"},{"name":"Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain"},{"name":"Institute of Neuroscience, University of Granada, Centro de Investigaci\u00f3n Biom\u00e9dica (CIBM), Parque de Tecnol\u00f3gico de la Salud (PTS), 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Toledano","sequence":"additional","affiliation":[{"name":"Instituto Investigaci\u00f3n Biosanitaria, ibs. Granada, 18012 Granada, Spain"},{"name":"Faculty of Dentistry, University of Granada, Colegio M\u00e1ximo de Cartuja s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Osorio","sequence":"additional","affiliation":[{"name":"Instituto Investigaci\u00f3n Biosanitaria, ibs. Granada, 18012 Granada, Spain"},{"name":"Faculty of Dentistry, University of Granada, Colegio M\u00e1ximo de Cartuja s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zagho, M.M., Hussein, E.A., and Elzatahry, A.A. (2018). Recent Overviews in Functional Polymer Composites for Biomedical Applications. Polymers, 10.","DOI":"10.3390\/polym10070739"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, H., Xu, M., Shi, R., Zhang, A., and Zhang, J. (2022). Advances in Electrostatic Spinning of Polymer Fibers Functionalized with Metal-Based Nanocrystals and Biomedical Applications. 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