Vascular endothelial growth factor-immobilized self-assembled monolayers on hydroxyapatite: Cell functions pertinent to angiogenesis and bone healing




Solomon, Kimberly D.

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Currently, tissue engineered constructs for critical sized bone defects are non-vascularized. There are many strategies being employed to promote vascularization including delivery of angiogenic growth factors such as vascular endothelial growth factor (VEGF). The overall aim of this study was to evaluate the use of self-assembled monolayers (SAMs) as a growth factor delivery mechanism that would simultaneously enhance angiogenic activity of endothelial cells and osteogenic activity of osteoblasts. The long-term goal of this study was to accelerate osseointegration of hydroxyapatite (HA) scaffolds with surrounding natural bone, ultimately allowing for larger implant size. In this study, HA discs and scaffolds were coated with SAMs, which were used to covalently bind VEGF. Using 11-phosphonoundecanoic acid (11-PUDA) and/or 16-phosphonohexadecanoic acid (16-PHDA), different SAM chain length ratios (11-PUDA:16-PHDA) were evaluated to determine differences in loading and release of VEGF. HA surfaces were characterized by contact angle, atomic force microscopy, and Fourier transform infra-red (FTIR) spectroscopy to ensure that SAMs and VEGF were attached. VEGF loading and release studies were performed, followed by endothelial cell studies to determine angiogenic response. Finally, co-culture studies were performed with osteoblast and endothelial cell controls to determine if co-culture enhanced the angiogenic effects of the developed VEGF delivery system.

It was found that SAMs of varied chain length ratios could be formed on HA surfaces. The SAM chain length ratio did not affect VEGF loading, and cumulative release was able to be quantified over time. However, the VEGF release profile was affected by SAM chain length ratio. Although it was inconclusive if the VEGF on HA discs invoked an angiogenic cell response, angiogenic response was confirmed on VEGF-incorporated 3-D scaffolds, as indicated by increases in metabolic activity, proliferation, angiogenic markers, and cell bridging. In conclusion, SAMs provide a feasible option for sustained VEGF delivery from HA surfaces to promote angiogenesis.


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angiogenesis, bone tissue engineering, hydroxyapatite, self-assembled monlayers, vascular endothelial growth factor



Biomedical Engineering