000088556 001__ 88556
000088556 005__ 20230921135432.0
000088556 0247_ $$2doi$$a10.3389/fbioe.2020.00336
000088556 0248_ $$2sideral$$a117355
000088556 037__ $$aART-2020-117355
000088556 041__ $$aeng
000088556 100__ $$0(orcid)0000-0002-0255-6200$$aNasello, Gabriele$$uUniversidad de Zaragoza
000088556 245__ $$aPrimary Human Osteoblasts Cultured in a 3D Microenvironment Create a Unique Representative Model of Their Differentiation Into Osteocytes
000088556 260__ $$c2020
000088556 5060_ $$aAccess copy available to the general public$$fUnrestricted
000088556 5203_ $$a{Microengineered systems provide an in vitro strategy to explore the variability of individual patient response to tissue engineering products, since they prefer the use of primary cell sources representing the phenotype variability. Traditional in vitro systems already showed that primary human osteoblasts embedded in a 3D fibrous collagen matrix differentiate into osteocytes under specific conditions. Here, we hypothesized that translating this environment to the organ-on-a-chip scale creates a minimal functional unit to recapitulate osteoblast maturation toward osteocytes and matrix mineralization. Primary human osteoblasts were seeded in a type I collagen hydrogel, to establish the role of lower (2.5 × 10<sup>5</sup> cells/ml) and higher (1 × 10<sup>6</sup> cells/ml) cell density on their differentiation into osteocytes. A custom semi-automatic image analysis software was used to extract quantitative data on cellular morphology from brightfield images. The results are showing that cells cultured at a high density increase dendrite length over time, stop proliferating, exhibit dendritic morphology, upregulate alkaline phosphatase (ALP) activity, and express the osteocyte marker dental matrix protein 1 (DMP1). On the contrary, cells cultured at lower density proliferate over time, do not upregulate ALP and express the osteoblast marker bone sialoprotein 2 (BSP2) at all timepoints. Our work reveals that microengineered systems create unique conditions to capture the major aspects of osteoblast differentiation into osteocytes with a limited number of cells. We propose that the microengineered approach is a functional strategy to create a patient-specific bone tissue model and investigate the individual osteogenic potential of the patient bone cells.
000088556 536__ $$9info:eu-repo/grantAgreement/EC/H2020/722535/EU/Predictive models and simulations in bone regeneration: a multiscale patient-specific approach/CuraBone$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 722535-CuraBone$$9info:eu-repo/grantAgreement/ES/MINECO/DPI2017-84780-C2-1-R
000088556 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000088556 590__ $$a5.89$$b2020
000088556 591__ $$aMULTIDISCIPLINARY SCIENCES$$b12 / 72 = 0.167$$c2020$$dQ1$$eT1
000088556 592__ $$a1.081$$b2020
000088556 593__ $$aBioengineering$$c2020$$dQ1
000088556 593__ $$aHistology$$c2020$$dQ1
000088556 593__ $$aBiotechnology$$c2020$$dQ1
000088556 593__ $$aBiomedical Engineering$$c2020$$dQ1
000088556 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000088556 700__ $$0(orcid)0000-0003-1958-4432$$aAlamán-Díez, Pilar$$uUniversidad de Zaragoza
000088556 700__ $$aSchiavi, Jessica
000088556 700__ $$0(orcid)0000-0002-2901-4188$$aPérez, María Ángeles$$uUniversidad de Zaragoza
000088556 700__ $$aMcNamara, Laoise
000088556 700__ $$0(orcid)0000-0002-9864-7683$$aGarcía-Aznar, José Manuel$$uUniversidad de Zaragoza
000088556 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000088556 773__ $$g8 (2020), 336 [14 pp]$$pFront. Bioeng. Biotechnol.$$tFrontiers in Bioengineering and Biotechnology$$x2296-4185
000088556 8564_ $$s1359619$$uhttps://zaguan.unizar.es/record/88556/files/texto_completo.pdf$$yVersión publicada
000088556 8564_ $$s35422$$uhttps://zaguan.unizar.es/record/88556/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000088556 909CO $$ooai:zaguan.unizar.es:88556$$particulos$$pdriver
000088556 951__ $$a2023-09-21-13:30:24
000088556 980__ $$aARTICLE