Iron Oxide‐Labeled Collagen Scaffolds for Non‐Invasive MR Imaging in Tissue Engineering

Abstract

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.

Imaging Strategies for Tissue Engineering Applications

“…In addition, SPIONs have also been used to directly label collagen scaffolds and degradation of the subcutaneously implanted scaffold was clearly visualized in vivo. 52 Hydrogel filaments containing gadolinium or SPIO were invented to be visualized by MRI and applied to embolization for the treatment of intracranial aneurysm. 53 More precise and accurate mechanical properties such as stiffness and elasticity can be assessed using magnetic resonance elastography (MRE), which uses low-frequency shear wave motion generated by an acoustic actuator coupled to the tissue of interest.…”

USPIO-labeled textile materials for non-invasive MR imaging of tissue-engineered vascular grafts

“…As recently demonstrated for USPIO-labeled collagen matrices [26], non-invasive MR imaging can also be employed to assess the degradation kinetics of tissue-engineered implant materials, and it can help to tailor the material characteristics and optimize them for different sites of implantation and/or different types of applications. By e.g.…”

Nondestructive monitoring of tissue-engineered constructs

“…USPIO nanoparticles possessing different surface functionalities were incorporated either physically or chemically into the scaffolds. Labeled scaffolds were shown to be highly biocompatible and suitable for tissue engineering applications [35,41].…”