Functionalization of Novel Theranostic Hydrogels with Kartogenin-Grafted USPIO Nanoparticles To Enhance Cartilage Regeneration

• Published in: ACS applied materials & interfaces Vol. 11; no. 38; pp. 34744 - 34754
• Main Authors: Yang, Wei, Zhu, Ping, Huang, Huanlei, Zheng, Yuanyuan, Liu, Jian, Feng, Longbao, Guo, Huiming, Tang, Shuo, Guo, Rui
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25-09-2019
• Subjects: Anilides - chemistry; Anilides - pharmacology; Animals; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; Cartilage - injuries; Cartilage - pathology; Cartilage - physiology; Cell Differentiation - drug effects; Chondrocytes - metabolism; Chondrocytes - pathology; Hydrogels - chemistry; Hydrogels - pharmacology; Magnetite Nanoparticles - chemistry; Magnetite Nanoparticles - therapeutic use; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - pathology; Phthalic Acids - chemistry; Phthalic Acids - pharmacology; Rabbits; Regeneration - drug effects; Theranostic Nanomedicine; magnetic resonance imaging (MRI); kartogenin; dextran; cartilage regeneration; hydrogels
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.9b12288

Here, kartogenin (KGN), an emerging stable nonprotein compound with the ability to promote differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes, was grafted onto the surface of modified ultrasmall superparamagnetic iron-oxide (USPIO) and then integrated into cellulose nanocrystal/dextran hydrogels. The hydrogels served as a carrier for the USPIO-KGN and a matrix for cartilage repair. We carried out in vitro and in vivo studies, the results of which demonstrated that KGN undergoes long-term stable sustained release, recruits endogenous host cells, and induces BMSCs to differentiate into chondrocytes, thus enabling in situ cartilage regeneration. Meanwhile, the USPIO-incorporated theranostic hydrogels exhibited a distinct magnetic resonance contrast enhancement and maintained a stable relaxation rate, with almost no loss, both in vivo and in vitro. According to noninvasive in vivo observation results and immunohistochemistry analyses, the regenerated cartilage tissue was very similar to natural hyaline cartilage. This innovative diagnosis and treatment system increases the convenience and effectiveness of chondrogenesis.