Doxycycline-doped membranes induced osteogenic gene expression on osteoblastic cells.

Manuel Toledano-Osorio, Francisco Javier Manzano-Moreno, Manuel Toledano, Raquel Osorio, Antonio L Medina-Castillo, Víctor J Costela-Ruiz, Concepción Ruiz

Journal: Journal of dentistry 2021;109():103676

PMID: 33891990

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Abstract

OBJECTIVES

To analyze how novel developed silicon dioxide composite membranes, functionalized with zinc or doxycycline, can modulate the expression of genes related to the osteogenic functional capacity of osteoblastic cells.

METHODS

The composite nanofibers membranes were manufactured by using a novel polymeric blend and 20 nm silicon dioxide nanoparticles (SiO-NPs). To manufacture the membranes, 20 nm SiO-NPs were added to the polymer solution and the resulting suspension was processed by electrospinning. In a second step, the membranes were functionalized with zinc or doxycycline. Then, they were subjected to MG63 osteoblast-like cells culturing for 48 h. After this time, real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to study the expression of Runx-2, OSX, ALP, OSC, OPG, RANKL, Col-I, BMP-2, BMP-7, TGF-β1, VEGF, TGF-βR1, TGF- βR2, and TGF-βR3. Mean comparisons were conducted by One-way ANOVA and Tukey tests (p < 0.05).

RESULTS

In general, the blending of SiO-NPs in the tested non-resorbable polymeric scaffold improves the expression of osteogenic genes over the control membranes. Doxycycline doping of experimental scaffolds attained the best results, encountering up-regulation of BMP-2, ALP, OPG, TGFβ-1 and TGFβ-R1. Membranes with zinc induced a significant increase in the expression of Col-I, ALP and TGF β1. Both, zinc and doxycycline functionalized membranes enormously down-regulated the expression of RANKL.

CONCLUSIONS

Zinc and doxycycline doped membranes are bioactive inducing overexpression of several osteogenic gene markers.

CLINICAL SIGNIFICANCE

Doxycycline doped membranes may be a potential candidate for use in GBR procedures in several challenging pathologies, including periodontal diseases.

Address: Biomaterials in Dentistry Research Group, Department of Stomatology, School of Dentistry, University of Granada, Spain; Medicina Clínica y Salud Pública PhD Programme, Spain.; Biomedical Group (BIO277), Department of Stomatology, School of Dentistry, University of Granada, Spain; Instituto Investigación Biosanitaria, ibs, Granada, Granada, Spain.; Biomaterials in Dentistry Research Group, Department of Stomatology, School of Dentistry, University of Granada, Spain. Electronic address: [email protected].; Biomaterials in Dentistry Research Group, Department of Stomatology, School of Dentistry, University of Granada, Spain.; NanoMyP®, Nanomateriales y Polimeros S.L., Spin-Off company of the University of Granada, Edificio BIC-Granada. Av. Innovación 1. 18016 - Armilla, Granada, Spain.; Instituto Investigación Biosanitaria, ibs, Granada, Granada, Spain; Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Spain.; Instituto Investigación Biosanitaria, ibs, Granada, Granada, Spain; Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Spain; Institute of Neuroscience, University of Granada, Centro de Investigación Biomédica (CIBM), Parque de Tecnológico de la Salud (PTS), Granada, Spain.

DOI: 10.1016/j.jdent.2021.103676

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MeSH Terms: Cell Differentiation, Doxycycline, Gene Expression, Osteoblasts, Osteogenesis, Silicon Dioxide