Institute of Biomaterials & Biomedical Engineering, The Edward S. Rogers Sr. Department of Electrical & Computer Engineering, Ted Rogers Centre for Heart Research, Translational Biology & Engineering Program, University of Toronto, 164 College Street, RS407, Toronto, ON, M5S 3G9, Canada.
Macromol Biosci. 2019 Apr;19(4):e1800330. doi: 10.1002/mabi.201800330. Epub 2019 Jan 15.
Biomaterial scaffolds are the cornerstone to supporting 3D tissue growth. Optimized scaffold design is critical to successful regeneration, and this optimization requires accurate knowledge of the scaffold's interaction with living tissue in the dynamic in vivo milieu. Unfortunately, non-invasive methods that can probe scaffolds in the intact living subject are largely underexplored, with imaging-based assessment relying on either imaging cells seeded on the scaffold or imaging scaffolds that have been chemically altered. In this work, the authors develop a broadly applicable magnetic resonance imaging (MRI) method to image scaffolds directly. A positive-contrast "bright" manganese porphyrin (MnP) agent for labeling scaffolds is used to achieve high sensitivity and specificity, and polydopamine, a biologically derived universal adhesive, is employed for adhering the MnP. The technique was optimized in vitro on a prototypic collagen gel, and in vivo assessment was performed in rats. The results demonstrate superior in vivo scaffold visualization and the potential for quantitative tracking of degradation over time. Designed with ease of synthesis in mind and general applicability for the continuing expansion of available biomaterials, the proposed method will allow tissue engineers to assess and fine-tune the in vivo behavior of their scaffolds for optimal regeneration.
生物材料支架是支持 3D 组织生长的基石。优化支架设计对于成功再生至关重要,而这种优化需要准确了解支架在动态体内环境中与活体组织的相互作用。不幸的是,能够在完整的活体研究对象中探测支架的非侵入性方法在很大程度上仍未得到充分探索,基于成像的评估方法要么依赖于对支架上接种的细胞进行成像,要么依赖于对化学改性的支架进行成像。在这项工作中,作者开发了一种广泛适用的磁共振成像(MRI)方法来直接对支架进行成像。使用正对比“亮”锰卟啉(MnP)试剂来标记支架,以实现高灵敏度和特异性,并且使用生物衍生的通用粘合剂聚多巴胺(polydopamine)来粘附 MnP。该技术在原型胶原凝胶中进行了体外优化,并在大鼠体内进行了评估。结果表明,该技术能够更好地在体内可视化支架,并有可能随着时间的推移进行定量跟踪降解。该方法在设计时考虑了易于合成,并具有广泛的适用性,可用于不断扩展的可用生物材料,这将使组织工程师能够评估和微调支架的体内行为,以实现最佳再生。