Labeling of Collagen Type I Templates with a Naturally Derived Contrast Agent for Noninvasive MR Imaging in Soft Tissue Engineering

Abstract

In vivo monitoring of tissue-engineered constructs is important to assess their integrity, remodeling, and degradation. However, this is challenging when the contrast with neighboring tissues is low, necessitating labeling with contrast agents (CAs), but current CAs have limitations (i.e., toxicity, negative contrast, label instability, and/or inappropriate size). Therefore, a naturally derived hemin-L-lysine (HL) complex is used as a potential CA to label collagen-based templates for magnetic resonance imaging (MRI). Labeling does not change the basic characteristics of the collagen templates. When hybrid templates composed of collagen type I reinforced with degradable polymers are subcutaneously implanted in mice, longitudinal visualization by MRI is possible with good contrast and in correlation with template remodeling. In contrast, unlabeled collagen templates are hardly detectable and the fate of these templates cannot be monitored by MRI. Interestingly, tissue remodeling and vascularization are enhanced within HL-labeled templates. Thus, HL labeling is presented as a promising universal imaging marker to label tissue-engineered implants for MRI, which additionally seems to accelerate tissue regeneration.

MR and PET-CT monitoring of tissue-engineered vascular grafts in the ovine carotid artery

“…Recently, a naturally derived hemin-L-lysine (HL) complex was used to label hybrid templates composed of collagen type I reinforced with degradable polymers that were subcutaneously implanted in mice. This enabled the longitudinal visualization by MRI with good contrast and in correlation with scaffold remodeling [71]. Alternatively to 1 H MRI as performed in this study, 19 F MRI can also be applied to image vascular scaffolds if novel fluorinated polymeric materials are incorporated that possess magnetically visible 19 F atoms with high mobility, enabled by the amorphous structure of the polymers [72].…”

Enhancing X-ray Attenuation of 3D Printed Gelatin Methacrylate (GelMA) Hydrogels Utilizing Gold Nanoparticles for Bone Tissue Engineering Applications

“…For instance, even though histological techniques provide crucial information, these destructive imaging techniques are incapable of providing 3D information, which significantly hinders the use of such conventional methods for in vivo and preclinical applications [ 3 ]. Therefore, an increasing number of recent tissue engineering studies feature the compatibility of the utilized 3D scaffolds with different advanced imaging modalities [ 4 , 5 , 6 , 7 ].…”

Lifelike Transformative Materials for Biohybrid Implants: Inspired by Nature, Driven by Technology

“…However, imaging can do much more. For example, diagnostic markers can significantly improve the localization of biohybrid systems, as demonstrated by the CT imaging of biohybrid scaffold materials labeled with gold [85] and barium nanoparticles, [86] and MRI with manganese-loaded porphyrins, [87] ferritin derivatives, [88] and SPIONs. [46,89] Furthermore, 19 F-containing markers are often used for MRI labeling because fluorine is not usually found at significant concentrations in human soft tissues.…”