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Int. J. Mol. Sci. 2017, 18(11), 2478; https://doi.org/10.3390/ijms18112478

Vascular Endothelial Growth Factor Sequestration Enhances In Vivo Cartilage Formation

1
Department of Surgery, University Hospital Basel, and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland
2
Brighton Studies in Tissue-mimicry and Aided Regeneration, Centre for Regenerative Medicine and Devices, University of Brighton, Huxley Building Lewes Road, Brighton BN2 4GJ, UK
Current Address: Anika Therapeutics Srl, Corso Stati Uniti 4/U, 35127 Padova, Italy.
*
Author to whom correspondence should be addressed.
Received: 10 October 2017 / Revised: 1 November 2017 / Accepted: 15 November 2017 / Published: 21 November 2017
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Abstract

Autologous chondrocyte transplantation for cartilage repair still has unsatisfactory clinical outcomes because of inter-donor variability and poor cartilage quality formation. Re-differentiation of monolayer-expanded human chondrocytes is not easy in the absence of potent morphogens. The Vascular Endothelial Growth Factor (VEGF) plays a master role in angiogenesis and in negatively regulating cartilage growth by stimulating vascular invasion and ossification. Therefore, we hypothesized that its sole microenvironmental blockade by either VEGF sequestration by soluble VEGF receptor-2 (Flk-1) or by antiangiogenic hyperbranched peptides could improve chondrogenesis of expanded human nasal chondrocytes (NC) freshly seeded on collagen scaffolds. Chondrogenesis of several NC donors was assessed either in vitro or ectopically in nude mice. VEGF blockade appeared not to affect NC in vitro differentiation, whereas it efficiently inhibited blood vessel ingrowth in vivo. After 8 weeks, in vivo glycosaminoglycan deposition was approximately two-fold higher when antiangiogenic approaches were used, as compared to the control group. Our data indicates that the inhibition of VEGF signaling, independently of the specific implementation mode, has profound effects on in vivo NC chondrogenesis, even in the absence of chondroinductive signals during prior culture or at the implantation site. View Full-Text
Keywords: chondrogenesis; dendron; soluble VEGF receptor-2; nasal chondrocyte; collagen scaffold chondrogenesis; dendron; soluble VEGF receptor-2; nasal chondrocyte; collagen scaffold
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Medeiros Da Cunha, C.M.; Perugini, V.; Bernegger, P.; Centola, M.; Barbero, A.; Guildford, A.L.; Santin, M.; Banfi, A.; Martin, I.; Marsano, A. Vascular Endothelial Growth Factor Sequestration Enhances In Vivo Cartilage Formation. Int. J. Mol. Sci. 2017, 18, 2478.

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