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MRI method for labeling and imaging decellularized extracellular matrix scaffolds for tissue engineering
Author(s) -
Szulc Daniel Andrzej,
Ahmadipour Mohammadali,
Aoki Fabio Gava,
Waddell Thomas K.,
Karoubi Golnaz,
Cheng HaiLing Margaret
Publication year - 2020
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.28072
Subject(s) - decellularization , in vivo , extracellular matrix , biomedical engineering , ex vivo , chemistry , matrix (chemical analysis) , biophysics , medicine , biology , biochemistry , chromatography , microbiology and biotechnology
Purpose To develop a facile method for labeling and imaging decellularized extracellular matrix (dECM) scaffolds intended for regenerating 3D tissues. Methods A small molecule manganese porphyrin, MnPNH 2 , was synthesized and used to label dECM scaffolds made from porcine bladder and trachea and murine whole lungs. The labeling protocol was optimized on bladder dECM, and imaging on a 3T clinical scanner was performed to assess reductions in T 1 and T 2 relaxation times. In vivo MRI was performed on dECM injected in the rat dorsum to verify sensitivity of detection. Toxicity assays for cell viability, metabolism, and proliferation were performed on human umbilical vein endothelial cells. The incorporation of MnPNH 2 and its long‐term retention in dECM were assessed on transmission electron microscopy and ultraviolet absorbance of eluted MnPNH 2 over time. Results All tissues, including thick whole 3D organs, were uniformly labeled and demonstrated high signal‐to‐noise on MRI. A nearly 10‐fold reduction in T 1 was consistently obtained at a labeling dose of 0.4 mM, and even 0.2 mM provided sufficient contrast in vivo and ex vivo. No toxicity was observed up to 0.4 mM, the maximum tested. Binding studies suggested nonspecific association, and retention studies in the labeled whole decellularized lungs revealed less than 20% MnPNH 2 loss over 30 days, the majority occurring in the first 3 days after labeling. Conclusion The proposed labeling method is the first report for visualizing dECM on MRI and has the potential for long‐term monitoring and optimization of dECM‐based organ tissue engineering.