The effects of VEGF-centered biomimetic delivery of growth factors on bone regeneration.

It is accepted that biomimetic supply of signaling molecules during bone regeneration can provide an appropriate environment for accelerated new bone formation. In this study, we developed a growth factor delivery system based on porous particles and a thermosensitive hydrogel that allowed fast, continuous, and delayed/continuous release of growth factors to mimic their biological production during bone regeneration. It was observed that the Continuous group (continuous release of growth factors) provides a better environment for the osteogenic differentiation of hPDCs than the Biomimetic group (biomimetic release of growth factors), and thus is anticipated to promote bone regeneration. However, contrary to expectation, the Biomimetic group promoted significant new bone formation compared to the Continuous group. From the systematic cell culture experiments, the initial supply of VEGF was considered to have more favorable effects on the osteoclastogenesis than osteogenesis, which may hinder bone regeneration. Our results indicated that the continuous supply of VEGF (in particular, at early stage) from VEGF-loaded biomaterial might not be conducive to new bone formation. Therefore, we suggest that a biomimetic supply of growth factors is a more pivotal parameter for sufficient tissue regeneration. Its use as a molecular delivery system may also serve as a useful tool for the investigation of biological processes and molecules during tissue regeneration processes.