Inhibition of Angiogenesis Impairs Bone Healing in an In Vivo Murine Rapid Resynostosis Model.

Related Articles

Inhibition of Angiogenesis Impairs Bone Healing in an In Vivo Murine Rapid Resynostosis Model.

J Biomed Mater Res A. 2017 Jun 07;:

Authors: Hyzy SL, Kajan I, Wilson DS, Lawrence KA, Mason D, Williams JK, Olivares-Navarrete R, Cohen DJ, Schwartz Z, Boyan BD

Abstract
Biologics can improve bone formation, but may diffuse away from sites of therapeutic need. We developed a click-chemistry hydrogel that rapidly polymerizes in situ to control delivery of biologics during post-suturectomy resynostosis in 21-d-old male mice. Here, we used this model to determine the role of angiogenesis in post-suturectomy resynostosis and examine whether controlled release of angiogenesis inhibitors could delay bone regeneration. Hydrogels [DB-co-PEG/poly(TEGDMA)-co-(N3-TEGDMA)] were produced containing anti-angiogenic compounds (anti-VEGFA-antibody or HIF1α-inhibitor topotecan). Bioactivity in vitro was assessed by tube length and branching points of endothelial cells in hydrogel-conditioned media. In vivo effects were examined 14 d post-suturectomy, based on the temporal analysis of angiogenic mRNAs during resynostosis following posterior frontal suture removal. MicroCT was used to quantify angiogenesis in contrast-agent-perfused blood vessels and bone defect size in defects receiving hydrogel, anti-VEGFA/hydrogel, or topotecan/hydrogel. Shorter endothelial tube length and less branching were seen in inhibitor-conditioned media (topotecan>AbVEGFA). In vivo, both compounds inhibited angiogenesis compared to hydrogel-only. Anti-VEGFA/hydrogel reduced resynostosis compared to empty defects, but topotecan/hydrogel blocked bone regeneration. We demonstrate that anti-angiogenic compounds can be incorporated into a spontaneously polymerizing hydrogel and remain active over 14d in vitro and in vivo. Moreover, bone formation can be delayed by inhibiting neovascularization, suggesting possible use as a therapeutic to control resynostosis following suturectomies and potential applications in other conditions where rapid osteogenesis is not desired. This article is protected by copyright. All rights reserved.

PMID: 28589712 [PubMed - as supplied by publisher]

http://ift.tt/2rZ36Kr