In vitro evaluation of FL118 and 9-Q20 cytotoxicity and cellular uptake in 2D and 3D different cell models

Weng, Qi; Zhou, Leilei; Xia, Lihua; Zheng, Yixin; Zhang, Xiangli; Li, Fengzhi; Li, Qingyong

doi:10.1007/s00280-019-03846-x

Cited by 13 publications

(17 citation statements)

References 37 publications

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“…For the initial assessment of such biological responses, the present study employed an in vitro tridimensional model based on a spheroidal 3D culture of osteoblastic cells, as proposed previously [49]. The use of tridimensional cell aggregates can increase the similarity with the microenvironment present on in vivo tissues, with more information than 2D cells models [84,85], as cells can remain integrated into the spheroid or migrate and proliferate to colonize a material surface, depending on its osteoconductive properties. The primary human osteoblast spheroids also allow the focal seeding of cells in a specific point of contact, providing insights on the migration and extent of occupation of a material surface over time.…”

Section: Discussionmentioning

confidence: 99%

“…To assess the efficacy of surface functionalization in biocompatible biomaterials, the majority of in vitro assessments are performed through direct cell seeding, which creates a monolayer over the material surface [39,40]. However, new paradigms of in vitro studies in the 21st century include the use of microtissues and 3D culture models [41]. Compared to the 2D-monolayer model, the 3D cultured model can mimic the microenvironment in native tissue, with more precise tissue response simulation.…”

Section: Introductionmentioning

confidence: 99%

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Biomimetic Mineralization on 3d Printed Pla Scaffolds: On the Response of Human Primary Osteoblasts Spheroids and in Vivo Implantation

Maia-Pinto

Brochado

Teixeira

et al. 2020

Preprint

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This study aimed to assess the response of 3D printed PLA scaffolds biomimetically coated with apatite on human primary osteoblast spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution, and characterized by physical-chemical, morphological, and mechanical properties. The in vitro biological response was assessed with human primary osteoblast (HOb) spheroids. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, covered by apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 (PLA-CaP+rhBMP-2) on critical-sized defects (8 mm) of rat calvaria. Increased cell adhesion and in vitro release of growth factors (PDGF, bFGF, VEGF) was observed for PLA-CaP scaffolds when pre-treated with FBS. PLA-CaP+BMP2 presented higher values of newly formed bone (NFB) than other groups at all experimental periods (p&lt;0.05), attaining 44.85% of NFB after 6 months. These findings indicate that functionalization of PLA scaffolds with biomimetic apatite can improve its biological properties in the presence of complex biological media. Its association with BMP2 may enhance bone repair, suggesting this strategy as a promising candidate for bone tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biomimetic Mineralization on 3d Printed Pla Scaffolds: On the Response of Human Primary Osteoblasts Spheroids and in Vivo Implantation

Maia-Pinto

Brochado

Teixeira

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Biomimetic Mineralization on 3D Printed PLA Scaffolds: On the Response of Human Primary Osteoblasts Spheroids and In Vivo Implantation

et al. 2020

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This study aimed to assess the response of 3D printed polylactic acid (PLA) scaffolds biomimetically coated with apatite on human primary osteoblast (HOb) spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution to promote apatite deposition, and characterized by physical-chemical, morphological, and mechanical properties. PLA-CaP scaffolds with interconnected porous and mechanical properties suitable for bone repairing were produced with reproducibility. The in vitro biological response was assessed with human primary osteoblast spheroids. Increased cell adhesion and the rise of in vitro release of growth factors (Platelet-Derived Growth Factor (PDGF), Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) was observed for PLA-CaP scaffolds, when pre-treated with fetal bovine serum (FBS). This pre-treatment with FBS was done in a way to enhance the adsorption of serum proteins, increasing the number of bioactive sites on the surface of scaffolds, and to partially mimic in vivo interactions. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, coated with apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 on critical-sized defects (8 mm) of rat calvaria. PLA-CaP+rhBMP2 presented higher values of newly formed bone (NFB) than other groups at all in vivo experimental periods (p < 0.05), attaining 44.85% of NFB after six months. These findings indicated two new potential candidates as alternatives to autogenous bone grafts for long-term treatment: (i) 3D-printed PLA-CaP scaffold associated with spheroids, since it can reduce the time of repair in situ by expression of biomolecules and growth factors; and (ii) 3D-printed PLA-CaP functionalized rhBMP2 scaffold, a biocompatible, bioactive biomaterial, with osteoconductivity and osteoinductivity.

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“…It turned out that while each of the five compounds show significant antitumor activity, FL118 was the top compound, possessing exceptional efficacy to eliminate human xenograft tumor without relapse over a period of 60 days in a high percentage of human tumors in animal models [63,68]. Interestingly, 3-dimentional (3D) cell models were recently developed for testing FL118 and several of the FL118 analogs [69,70]. However, whether the 3D cell models could replace the early stage in vivo animal testing for cost-effectiveness and selection of the future FL118 analogs remains to be investigated.…”

Section: Fl118mentioning

confidence: 99%

Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study?

Aljahdali

Ling

2019

J Exp Clin Cancer Res

Self Cite

185

171

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Survivin (also named BIRC5) is a well-known cancer therapeutic target. Since its discovery more than two decades ago, the use of survivin as a target for cancer therapeutics has remained a central goal of survivin studies in the cancer field. Many studies have provided intriguing insight into survivin's functional role in cancers, thus providing promise for survivin as a cancer therapeutic target. Despite this, moving survivin-targeting agents into and through the clinic remains a challenge. In order to address this challenge, we may need to rethink current strategies in order to develop a new mindset for targeting survivin. In this Review, we will first summarize the current survivin mechanistic studies, and then review the status of survivin cancer therapeutics, which is classified into five categories: (i) survivin-partner protein interaction inhibitors, (ii) survivin homodimerization inhibitors, (iii) survivin gene transcription inhibitors, (iv) survivin mRNA inhibitors and (v) survivin immunotherapy. We will then provide our opinions on cancer therapeutics using survivin as a target, with the goal of stimulating discussion that might facilitate translational research for discovering improved strategies and/or more effective anticancer agents that target survivin for cancer therapy.

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In vitro evaluation of FL118 and 9-Q20 cytotoxicity and cellular uptake in 2D and 3D different cell models

Cited by 13 publications

References 37 publications

Biomimetic Mineralization on 3d Printed Pla Scaffolds: On the Response of Human Primary Osteoblasts Spheroids and in Vivo Implantation

Biomimetic Mineralization on 3d Printed Pla Scaffolds: On the Response of Human Primary Osteoblasts Spheroids and in Vivo Implantation

Biomimetic Mineralization on 3D Printed PLA Scaffolds: On the Response of Human Primary Osteoblasts Spheroids and In Vivo Implantation

Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study?

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