Improving vascularization of engineered bone through the generation of pro-angiogenic effects in co-culture systems

Unger, Ronald E.; Dohle, Eva; Kirkpatrick, Charles James

doi:10.1016/j.addr.2015.03.012

Cited by 96 publications

(78 citation statements)

References 115 publications

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“…Many research efforts in prevascularized tissue engineering have relied on the spontaneous organization of endothelial cells to form vascular networks on scaffolds [16][17][18], in extracellular matrix analogs [4,19], or in cellular aggregates with other cells [20,21]. These studies show that Glossary Anastomosis: in the context of angiogenesis, the connection of two vascular structures.…”

Section: Natural Organization Of Endothelial Cells In Engineered Tissuesmentioning

confidence: 96%

Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks

Rouwkema

Khademhosseini

2016

Trends in Biotechnology

508

453

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Section: Natural Organization Of Endothelial Cells In Engineered Tissuesmentioning

confidence: 96%

Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks

Rouwkema

Khademhosseini

2016

Trends in Biotechnology

508

453

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“…For instance, BM-MSCs were used to generate blood vessels also seeded onto a scaffold with endothelial cells (Fedorovich et al, 2010; Gao et al, 2014). Indeed, the inefficient stimulus for a rapid development of new blood vessels that invade the coculture grafts may explain the fail in proving bone formation using this method (Liu et al, 2015a,b; Unger et al, 2015), making this approach still limited.…”

Section: Cell Sourcementioning

confidence: 99%

Biofabrication and Bone Tissue Regeneration: Cell Source, Approaches, and Challenges

Orciani

Fini

Primio

et al. 2017

Front. Bioeng. Biotechnol.

102

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The growing occurrence of bone disorders and the increase in aging population have resulted in the need for more effective therapies to meet this request. Bone tissue engineering strategies, by combining biomaterials, cells, and signaling factors, are seen as alternatives to conventional bone grafts for repairing or rebuilding bone defects. Indeed, skeletal tissue engineering has not yet achieved full translation into clinical practice because of several challenges. Bone biofabrication by additive manufacturing techniques may represent a possible solution, with its intrinsic capability for accuracy, reproducibility, and customization of scaffolds as well as cell and signaling molecule delivery. This review examines the existing research in bone biofabrication and the appropriate cells and factors selection for successful bone regeneration as well as limitations affecting these approaches. Challenges that need to be tackled with the highest priority are the obtainment of appropriate vascularized scaffolds with an accurate spatiotemporal biochemical and mechanical stimuli release, in order to improve osseointegration as well as osteogenesis.

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“…Based on these findings, the present work intended to evaluate the potential of VEGF loaded onto the scaffolds to stimulate vascularisation -as a first step towards the envisaged in vivo application. In our co-culture system, human endothelial cells were cultivated together with osteogenically induced hBMSC in order to combine two cell types relevant for bone regeneration and facilitate the cellular crosstalk of bone and endothelial cells, which is known to promote the formation of prevascular networks by production of pro-angiogenic factors (Unger et al, 2015). Co-cultivation of both cell types resulted in the spontaneous formation of rather weak tubular structures, capable of sprouting into the porous scaffold.…”

Section: Cultivation Of Hbmsc On Heparin-modified Scaffoldsmentioning

confidence: 99%

Heparin modification of a biomimetic bone matrix modulates osteogenic and angiogenic cell response in vitro

Quade¹,

Knaack²,

Weber³

et al. 2017

eCM

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In this study, the effect of heparin-modified collagen type I/hydroxyapatite (HA) nanocomposites on key processes of bone regeneration -osteogenesis and angiogenesiswas characterised in vitro. Two approaches were applied for heparin modification: it was either integrated during material synthesis (in situ) or added to the porous scaffolds after their fabrication (post). Cultivation of human bone marrow-derived stromal cells (hBMSC), in heparinmodified versus heparin-free scaffolds, revealed a positive effect of the heparin modification on their proliferation and osteogenic differentiation. The amount of heparin rather than the method used for modification influenced the cell response favouring proliferation at smaller amount (30 mg/g collagen) and differentiation at larger amount (150 mg/g collagen). A co-culture of human umbilical vein endothelial cells (HUVEC) and osteogenically induced hBMSC was applied for in vitro angiogenesis studies. Pre-vascular networks have formed in the porous structure of scaffolds which were not modified with heparin or modified with a low amount of heparin (30 mg/g collagen).The modification with higher heparin quantities seemed to inhibit tubule formation. Pre-loading of the scaffolds with VEGF influenced formation and stability of the prevascular structures depending on the presence of heparin: In heparin-free scaffolds, induction of tubule formation and sprouting was more pronounced whereas heparinmodified scaffolds seemed to promote stabilisation of the pre-vascular structures. In conclusion, the modification of mineralised collagen with heparin by using both approaches was found to modulate cellular processes essential for bone regeneration; the amount of heparin has been identified to be crucial to direct cell responses.

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Improving vascularization of engineered bone through the generation of pro-angiogenic effects in co-culture systems

Cited by 96 publications

References 115 publications

Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks

Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks

Biofabrication and Bone Tissue Regeneration: Cell Source, Approaches, and Challenges

Heparin modification of a biomimetic bone matrix modulates osteogenic and angiogenic cell response in vitro

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