Theranostics 2018; 8(4):1146-1158. doi:10.7150/thno.22514 This issue

Research Paper

Non-invasive monitoring of in vivo hydrogel degradation and cartilage regeneration by multiparametric MR imaging

Zelong Chen1*, Chenggong Yan1*, Shina Yan2, Qin Liu1, Meirong Hou1, Yikai Xu1✉, Rui Guo2✉

1. Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;
2. Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
* These two authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Chen Z, Yan C, Yan S, Liu Q, Hou M, Xu Y, Guo R. Non-invasive monitoring of in vivo hydrogel degradation and cartilage regeneration by multiparametric MR imaging. Theranostics 2018; 8(4):1146-1158. doi:10.7150/thno.22514. Available from

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Graphic abstract

Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering. However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging.

Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months.

Results: USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate. Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling in vitro. CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends in vivo. The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations.

Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration.

Keywords: non-invasive monitoring, ultrasmall superparamagnetic iron oxide (USPIO), magnetic resonance imaging, hydrogel degradation, cartilage regeneration