Influence of scaffold properties on the inter-relationship between human bone marrow derived stromal cells and endothelial cells in pro-osteogenic conditions

Stoppato, Matteo; Stevens, Hazel Y.; Carletti, Eleonora; Migliaresi, Claudio; Motta, Antonella; Guldberg, Robert E.

doi:10.1016/j.actbio.2015.07.013

Cited by 22 publications

(12 citation statements)

References 51 publications

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“…It has been reported that coculture of endothelial cells with osteoblasts derived from MSCs enhanced tube formation in vitro on 3D scaffolds due to the production of cytokines and angiogenic growth factors, with scaffold composition and structure affecting this cellular interplay . As an example, the addition of silk fibroin nanofibers to poly ( d , l ‐lactic acid) salt‐leached scaffolds with similar porosity and pore size distribution, which were otherwise highly suitable for coculture, affected endothelial cell and osteoblast response in an inhibitory way . The work of Stoppato et al has nicely shown that either a synergistic or depletive behavior of endothelial and bone cells can be observed depending on certain scaffold architectural and compositional features.…”

Section: Resultsmentioning

confidence: 99%

Pore Size Distribution and Blend Composition Affect In Vitro Prevascularized Bone Matrix Formation on Poly(Vinyl Alcohol)/Gelatin Sponges

Ossa

Trombi

D’Alessandro

et al. 2017

Macro Materials & Eng

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This study aims at identifying compositional and architectural (pore size and distribution) parameters of biocompatible scaffolds, which can be best suitable for both osteoblasts and endothelial cells to produce optimized 3D cocultured constructs. Spongy scaffolds are prepared using poly(vinyl alcohol) (PVA) and gelatin (G) at different weight compositions (PVA/G range: 100/0â\u80\u9350/50, w/w) via emulsion and freeze-drying. The higher the gelatin content, the larger is the volume occupied by higher size pores. Human umbilical vein endothelial cells and human mesenchymal stromal cells are independently differentiated on the scaffolds to select the best candidate for the coculture. The results of metabolic activity and histology on single platforms show both cell- and material-type dependent outcomes. PVA/G 80/20 scaffolds are finally selected and allow the formation of mineralized matrix containing organized endothelial-like structures. This study highlights the need for systematic investigations on multifactorial parameters of scaffolds to improve vascularized bone substitutes

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Section: Resultsmentioning

confidence: 99%

Pore Size Distribution and Blend Composition Affect In Vitro Prevascularized Bone Matrix Formation on Poly(Vinyl Alcohol)/Gelatin Sponges

Ossa

Trombi

D’Alessandro

et al. 2017

Macro Materials & Eng

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“…Stoppato et al . reported that enhanced osteogenic differentiation was observed in hMSC/HUVEC cocultures on silk fibroin-free scaffolds compared with hMSCs cultured alone or on scaffolds with silk fibroin; in contrast, coculturing on silk fibroin-coatings promoted EC growth 14 . Furthermore, Guerrero’s group demonstrated that the combination of hMSC/EC coculture and 3D microenvironment—provided by a polysaccharide-based scaffold—favored hMSC osteogenesis 21 .…”

Section: Introductionmentioning

confidence: 98%

Angiogenic and Osteogenic Synergy of Human Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells Cocultured on a Nanomatrix

Chen

Deng

Porter

et al. 2018

Sci Rep

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To date, bone tissue regeneration strategies lack an approach that effectively provides an osteogenic and angiogenic environment conducive to bone growth. In the current study, we evaluated the osteogenic and angiogenic response of human mesenchymal stem cells (hMSCs) and green fluorescent protein-expressing human umbilical vein endothelial cells (GFP-HUVECs) cocultured on a self-assembled, peptide amphiphile nanomatrix functionalized with the cell adhesive ligand RGDS (PA-RGDS). Analysis of alkaline phosphatase activity, von Kossa staining, Alizarin Red quantification, and osteogenic gene expression, indicates a significant synergistic effect between the PA-RGDS nanomatrix and coculture that promoted hMSC osteogenesis. In addition, coculturing on PA-RGDS resulted in enhanced HUVEC network formation and upregulated vascular endothelial growth factor gene and protein expression. Though PA-RGDS and coculturing hMSCs with HUVECs were each previously reported to individually enhance hMSC osteogenesis, this study is the first to demonstrate a synergistic promotion of HUVEC angiogenesis and hMSC osteogenesis by integrating coculturing with the PA-RGDS nanomatrix. We believe that using the combination of hMSC/HUVEC coculture and PA-RGDS substrate is an efficient method for promoting osteogenesis and angiogenesis, which has immense potential as an efficacious, engineered platform for bone tissue regeneration.

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“…This has prompted many researchers to develop strategies for eliciting vascularization and thus to provide adequate oxygen and nutrients to the core of the constructs . The majority of these studies rely on the self‐organization of endothelial and supporting cells, which requires long‐term in vitro cultures and efficient transport of nutrients when embedded in large 3D constructs …”

Section: Discussionmentioning

confidence: 99%

Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels

Arrigoni

Bongio

Talò

et al. 2016

Adv Healthcare Materials

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A major challenge in the development of clinically relevant 3D tissue constructs is the formation of vascular networks for oxygenation, nutrient supply, and waste removal. To this end, this study implements a multimodal approach for the promotion of vessel-like structures formation in stiff fibrin hydrogels. Computational simulations have been performed to identify the easiest microchanneled configuration assuring normoxic conditions throughout thick cylindrical hydrogels (8 mm height, 6 mm ∅), showing that in our configuration a minimum of three microchannels (600 μm ∅), placed in a non-planar disposition, is required. Using small hydrogel bricks with oxygen distribution equal to the microchanneled configuration, this study demonstrates that among different culture conditions, co-culture of mesenchymal and endothelial cells supplemented with ANG-1 and VEGF leads to the most developed vascular network. Microchanneled hydrogels have been then cultured in the same conditions both statically and in a bioreactor for 7 d. Unexpectedly, the combination between shear forces and normoxic conditions is unable to promote microvascular networks formation in three-channeled hydrogels. Differently, application of either shear forces or normoxic conditions alone results in microvessels outgrowth. These results suggest that to induce angiogenesis in engineered constructs, complex interactions between several biochemical and biophysical parameters have to be modulated.

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Influence of scaffold properties on the inter-relationship between human bone marrow derived stromal cells and endothelial cells in pro-osteogenic conditions

Cited by 22 publications

References 51 publications

Pore Size Distribution and Blend Composition Affect In Vitro Prevascularized Bone Matrix Formation on Poly(Vinyl Alcohol)/Gelatin Sponges

Pore Size Distribution and Blend Composition Affect In Vitro Prevascularized Bone Matrix Formation on Poly(Vinyl Alcohol)/Gelatin Sponges

Angiogenic and Osteogenic Synergy of Human Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells Cocultured on a Nanomatrix

Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels

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