<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>2215-3411</journal-id>
<journal-title><![CDATA[Odovtos International Journal of Dental Sciences]]></journal-title>
<abbrev-journal-title><![CDATA[Odovtos]]></abbrev-journal-title>
<issn>2215-3411</issn>
<publisher>
<publisher-name><![CDATA[Facultad de Odontología. Universidad de Costa Rica]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S2215-34112022000100044</article-id>
<article-id pub-id-type="doi">10.15517/ijds.2022.49151</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[3D spheroid cell cultures and their role in bone regeneration: a systematic review]]></article-title>
<article-title xml:lang="es"><![CDATA[Cultivos de esferoides 3D y su papel en la regeneración ósea: una revisión sistemática]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cuevas-González]]></surname>
<given-names><![CDATA[María Verónica]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Suaste-Olmos]]></surname>
<given-names><![CDATA[Fernando]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cuevas-González]]></surname>
<given-names><![CDATA[Juan Carlos]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Álvarez-Pérez]]></surname>
<given-names><![CDATA[Marco Antonio]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,National Autonomous University of Mexico Faculty of Dentistry Postgraduate Studies and Research Division]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,National Autonomous University of Mexico Institute of Cellular Physiology ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Autonomous University of Ciudad Juárez Institute of Biomedical Sciences Department of Stomatology]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,National Autonomous University of Mexico Faculty of Dentistry Postgraduate Studies and Research Division]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Mexico</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>04</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>04</month>
<year>2022</year>
</pub-date>
<volume>24</volume>
<numero>1</numero>
<fpage>44</fpage>
<lpage>57</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.sa.cr/scielo.php?script=sci_arttext&amp;pid=S2215-34112022000100044&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.sa.cr/scielo.php?script=sci_abstract&amp;pid=S2215-34112022000100044&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.sa.cr/scielo.php?script=sci_pdf&amp;pid=S2215-34112022000100044&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract Recently, the 3D spheroid cell culture application has been extensively used in the treatment of bone defects. A wide variety of methodologies have been used, which has made the comparison of results complex. Therefore, this systematic review has two aims: (i) to perform an analysis focused on the role of 3D spheroid cell culture in bone regeneration strategies; and (ii) address the main challenges in clinical application. A search of the following keywords "3D cell culture", "spheroid", and "bone regeneration" was carried out in the PubMed, Scopus, and ScienceDirect databases and limited to the years 2010-2020. Studies were included if their primary objective was the behavior of cell aggregates to formed spheroids structures by different 3D cell culture techniques focused on the regeneration of bone tissue. To address the risk of bias for in vitro studies, the United States national toxicology program tool was applied, and descriptive statistics of the data were performed, with the SPSS V.22 program. A total of 16 studies were included, which met the established criteria corresponding to in vitro and in vitro/in vivo studies; most of these studies used stem cells for the 3D cell spheroids. The most often methods used for the 3D formation were low adherence surface and rotational methods, moreover, mesenchymal stem cells were the cell line most frequently used because of their regenerative potential in the field of bone tissue engineering. Although the advances in research on the potential use of 3D spheroids in bone regeneration have made great strides, the constant innovation in cell spheroid formation methodologies means that clinical application remains in the future as strategy for 3D tissue bioprinting.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen Recientemente, la aplicación del cultivo 3D de esferoides se ha utilizado ampliamente en el tratamiento de defectos óseos. La variedad de metodologías para lograr los cultivos 3D de esferoides ha hecho compleja la comparación de resultados. Por tanto, esta revisión sistemática tiene dos objetivos: (i) realizar un análisis centrado en el papel de los cultivos 3D de esferoides en las estrategias de regeneración ósea; y (ii) abordar los principales desafíos en la aplicación clínica. Se realizó una búsqueda de las siguientes palabras clave "cultivo celular 3D", "esferoide" y "regeneración ósea" en las bases de datos PubMed, Scopus y ScienceDirect y se limitó a los años 2010-2020. Se incluyeron los estudios si su principal objetivo era el comportamiento de agregados celulares para generar las estructuras esferoidales desarrollados por diferentes técnicas de cultivo celular 3D enfocadas a la regeneración del tejido óseo. Para abordar el riesgo de sesgo de los estudios in vitro, se aplicó la herramienta del programa nacional de toxicología de Estados Unidos y se realizaron estadísticas descriptivas de los datos, con el programa SPSS V.22. Se incluyeron un total de 16 estudios, que cumplieron con los criterios establecidos correspondientes a estudios in vitro e in vitro/in vivo; la mayoría de estos estudios utilizaron células troncales para generar los esferoides celulares 3D. Los métodos más utilizados para la formación de los esferoides 3D fueron la superficie de baja adherencia y los métodos de rotación, asimismo, la línea celular de células troncales mesenquimales fueron las más utilizadas debido a su gran potencial regenerativo en el campo de la ingeniería de tejidos óseos. Aunque los avances en la investigación sobre el uso potencial de los cultivos celulares de esferoides 3D en la regeneración ósea han logrado grandes avances, la constante innovación en las metodologías de la generación de esferoides 3D deja claro que la aplicación clínica de estos permanecerá en el futuro como estrategia en la bioimpresión tisular.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Bone tissue engineering]]></kwd>
<kwd lng="en"><![CDATA[3D cell culture]]></kwd>
<kwd lng="en"><![CDATA[3D spheroid]]></kwd>
<kwd lng="en"><![CDATA[Mesenchymal stem cells]]></kwd>
<kwd lng="en"><![CDATA[3D culture environment]]></kwd>
<kwd lng="en"><![CDATA[Bone regeneration]]></kwd>
<kwd lng="es"><![CDATA[Ingeniería de tejido óseo]]></kwd>
<kwd lng="es"><![CDATA[Cultivo celular 3D]]></kwd>
<kwd lng="es"><![CDATA[Esferoides]]></kwd>
<kwd lng="es"><![CDATA[Células troncales mesenquimales]]></kwd>
<kwd lng="es"><![CDATA[Ambientes de cultivos 3D]]></kwd>
<kwd lng="es"><![CDATA[Regeneración ósea]]></kwd>
</kwd-group>
</article-meta>
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