Universal Biofactor-Releasing Scaffold Enabling in Vivo Reloading

The supply of growth factors to engineered tissues is essential for many physiological processes. These processes include the proper organization of the cells into functioning tissues, maintenance of their viability, vasculogenesis, proliferation, and differentiation. Systems to efficiently control the release of growth factors were previously incorporated into tissue engineering scaffolds to affect cells. However, because the initial concentration of the factors in these systems is finite, their ability to provide a long-term physiological effect is limited. Here, we report on a new reloadable system in which 3D fibrous scaffolds conjugated with an anti His-tag antibody enable the retention and controlled release of any His-tag-modified proteinaceous growth factor. The scaffolds can be reloaded in vitro or in vivo with any His-tagged biomolecule at any time according to the physiological need. We show the ability of the scaffolds to release angiogenic factors in a static cell culture or under flow in a microfluidics device and effect on endothelial cells. We also demonstrate the potential of the system to be sequentially reloaded in vivo with various factors, and as a proof of concept, we provide evidence for the efficient in vivo vascularization of scaffolds after reloading with tagged VEGF.