Enhanced bone regeneration and visual monitoring via superparamagnetic iron oxide nanoparticle scaffold in rats

Journal of Tissue Engineering and Regenerative MedicineVolume 12, Issue 4 p. e2085-e2098 RESEARCH ARTICLE Enhanced bone regeneration and visual monitoring via superparamagnetic iron oxide nanoparticle scaffold in rats Shuying Hu, Shuying Hu Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, P. R. ChinaShuying Hu, Yi Zhou, and Yantao Zhao contributed equally to this work.Search for more papers by this authorYi Zhou, Yi Zhou Yixing People's Hospital, Yixing, P. R. ChinaShuying Hu, Yi Zhou, and Yantao Zhao contributed equally to this work.Search for more papers by this authorYantao Zhao, Yantao Zhao Beijing Engineering Research Center of Orthopaedic Implants, First Affiliated Hospital of CPLA General Hospital, Beijing, P. R. ChinaShuying Hu, Yi Zhou, and Yantao Zhao contributed equally to this work.Search for more papers by this authorYang Xu, Yang Xu Affiliated Stomatology Hospital of Soochow University, Suzhou, P. R. ChinaSearch for more papers by this authorFeimin Zhang, Feimin Zhang Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, P. R. ChinaSearch for more papers by this authorNing Gu, Ning Gu Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, P. R. China Suzhou Institute & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Suzhou, P. R. ChinaSearch for more papers by this authorJunqing Ma, Junqing Ma Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, P. R. ChinaSearch for more papers by this authorMark A. Reynolds, Mark A. Reynolds Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, USASearch for more papers by this authorYang Xia, Corresponding Author Yang Xia xiayang@njmu.edu.cn orcid.org/0000-0001-7962-8930 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, P. R. China Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, P. R. China Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, USA Correspondence Yang Xia, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, P. R. China. Email: xiayang@njmu.edu.cn Hockin H. K. Xu, Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA. Email: hxu@umaryland.eduSearch for more papers by this authorHockin H.K. Xu, Corresponding Author Hockin H.K. Xu hxu@umaryland.edu orcid.org/0000-0001-9175-9140 Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, USA Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, USA Department of Mechanical Engineering, University of Maryland Baltimore County, Baltimore County, MD, USA Correspondence Yang Xia, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, P. R. China. Email: xiayang@njmu.edu.cn Hockin H. K. Xu, Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA. Email: hxu@umaryland.eduSearch for more papers by this author Shuying Hu, Shuying Hu Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, P. R. ChinaShuying Hu, Yi Zhou, and Yantao Zhao contributed equally to this work.Search for more papers by this authorYi Zhou, Yi Zhou Yixing People's Hospital, Yixing, P. R. ChinaShuying Hu, Yi Zhou, and Yantao Zhao contributed equally to this work.Search for more papers by this authorYantao Zhao, Yantao Zhao Beijing Engineering Research Center of Orthopaedic Implants, First Affiliated Hospital of CPLA General Hospital, Beijing, P. R. ChinaShuying Hu, Yi Zhou, and Yantao Zhao contributed equally to this work.Search for more papers by this authorYang Xu, Yang Xu Affiliated Stomatology Hospital of Soochow University, Suzhou, P. R. ChinaSearch for more papers by this authorFeimin Zhang, Feimin Zhang Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, P. R. ChinaSearch for more papers by this authorNing Gu, Ning Gu Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, P. R. China Suzhou Institute & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Suzhou, P. R. ChinaSearch for more papers by this authorJunqing Ma, Junqing Ma Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, P. R. ChinaSearch for more papers by this authorMark A. Reynolds, Mark A. Reynolds Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, USASearch for more papers by this authorYang Xia, Corresponding Author Yang Xia xiayang@njmu.edu.cn orcid.org/0000-0001-7962-8930 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, P. R. China Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, P. R. China Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, USA Correspondence Yang Xia, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, P. R. China. Email: xiayang@njmu.edu.cn Hockin H. K. Xu, Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA. Email: hxu@umaryland.eduSearch for more papers by this authorHockin H.K. Xu, Corresponding Author Hockin H.K. Xu hxu@umaryland.edu orcid.org/0000-0001-9175-9140 Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, USA Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, USA Department of Mechanical Engineering, University of Maryland Baltimore County, Baltimore County, MD, USA Correspondence Yang Xia, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, P. R. China. Email: xiayang@njmu.edu.cn Hockin H. K. Xu, Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA. Email: hxu@umaryland.eduSearch for more papers by this author First published: 12 January 2018 https://doi.org/10.1002/term.2641Citations: 55 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract A main challenge for use of scaffolds in bone engineering involves non-invasive monitoring in vivo and enhanced bone regeneration. The tissue repair effect of superparamagnetic iron oxide nanoparticles (SPIONs) was demonstrated previously by our group. However, testing in vivo is needed to confirm in vitro results. Here, SPIONs loaded gelatin sponge (GS) was used as a scaffold (SPIONs-GS) and implanted in the incisor sockets of Sprague–Dawley rats. Incisor sockets filled with nothing and filled with GS served as controls. Rats were sacrificed at 2 and 4 weeks. A significant decrease in the signal intensity of T2-weighted magnetic resonance imaging (MRI) in the SPIONs-GS group was noted. Changes in image intensity of scaffolds (indicating scaffold degradation and interaction with host tissues) could be visually monitored over time. Microcomputed tomography showed that the SPIONs-GS group had more newly formed bone (64.44 ± 10.92 vs. 28.1 ± 4.49, p < .0001) and a better preserved alveolar ridge than blank control group at 4 weeks (0.962 ± 0.01 vs. 0.92 ± 0.01, p < .0001). Histology confirmed imaging results, showing good consistency in new bone formation and scaffold degradation. The number of SPIONs decreased rapidly with time due to quick degradation of GS, whereas the number of endocytic SPIONs in cells increased with time. These residual SPIONs, together with newly formed bone, could be detected by MRI at 4 weeks. Therefore, it was clear that SPIONs induced active osteogenesis. In conclusion, good visibility on MRI and enhanced regeneration of bone can be obtained by implanting SPIONs-GS in vivo without using an external magnetic field. CONFLICT OF INTEREST The authors have declared that there is no conflict of interest. Citing Literature Supporting Information Filename Description TERM_2641-sup-0001-Supporting materials.docWord document, 10.9 MB Figure S1. 3D reconstructions of rat mandibular bone defects at 0 day, 2 weeks and 4 weeks after surgery. Figure S2. H&E staining of the three groups at 2 and 4 weeks after surgery. Figure S3. Masson staining of the three groups 2 weeks after surgery. Figure S4. Model for mandibular length measurement. Figure S5. Magnetic resonance imaging (MRI) in vitro. (a) T2-weighted MRI of SPIONs solution with different concentrations in Eppendorf tubes and its T2-weighted values in relation to SPIONs concentrations (b). (c) Concentration of SPIONs samples tested by MRI in vitro (mg/mL). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume12, Issue4April 2018Pages e2085-e2098 RelatedInformation