Iron Oxide-labeled Collagen Scaffolds for Non-invasive MR Imaging in Tissue Engineering

Non-invasive imaging holds significant potential for implementation in tissue engineering. It can e.g. be used to monitor the localization and function of tissue-engineered implants, as well as their resorption and remodelling. Thus far, however, the vast majority of efforts in this area of research have focused on the use of ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticle-labeled cells, colonizing the scaffolds, to indirectly image the implant material. Reasoning that directly labeling scaffold materials might be more beneficial (enabling imaging also in case of non-cellularized implants), more informative (enabling the non-invasive visualization and quantification of scaffold degradation) and more easy to translate into the clinic (since cell-free materials are less complex from a regulatory point-of-view), we here prepared three different types of USPIO nanoparticles, and incorporated them both passively and actively (via chemical conjugation; during collagen crosslinking) into collagen-based scaffold materials. We furthermore optimized the amount of USPIO incorporated into the scaffolds, correlated the amount of entrapped USPIO with MR signal intensity, showed that the labeled scaffolds are highly biocompatible, demonstrated that scaffold degradation can be visualized using MRI and provided initial proof-of-principle for the in vivo visualization of the scaffolds. Consequently, USPIO-labeled scaffold materials seem to be highly suitable for image-guided tissue engineering applications.